Compounds and use thereof in the expansion of stem cells and/or progenitor cells
A compound and stem cell technology, applied in the field of expanding stem cells and/or progenitor cells, can solve the problems of not being able to provide enough HSCs for adult patients, and not being able to recover quickly and effectively
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Embodiment 1
[0177] Example 1: Preparation of Intermediate 1.4 (General Procedure A1)
[0178]
[0179] step 1
[0180] EtOH (4.16 mL, 71.3 mmol) was slowly added to an ice-cold suspension of NaH (60% w / w; 2.85 g, 71.3 mmol) in ether (51 mL). Additional EtOH (8.5ml) was added. Next a mixture of 1.1 (5.0 g, 59.4 mmol) and ethyl formate (5.02 mL, 62.4 mmol) was added dropwise. Additional ether (10 mL) was added and the mixture was stirred at room temperature overnight. Ether (50 mL) was added and the mixture was filtered. The solid was washed with ether (25 mL) and dried under reduced pressure to give the sodium salt 1.2; 1 H NMR (500MHz, DMSO-d 6 ) δppm 1.56 (quin, J = 7.90Hz, 2H), 1.87 (t, J = 7.72Hz, 2H), 2.24 (td, J = 7.30, 0.95Hz, 2H), 8.50, 8.87 (2s, 1H).
[0181] step 2
[0182] To 1.2 (7.30 g, 54.4 mmol) was added 2-cyanoacetamide (4.58 g, 54.4 mmol) in water (27.5 mL) followed by piperidine-1-acetate (1.38 g, 9.53 mmol) ( A solution in water (1.4 mL) was prepared by addin...
Embodiment 2
[0185] Example 2: Preparation of Intermediate 2.4 (Procedure A2)
[0186]
[0187] step 1
[0188] Add DMF (10.30 μl, 0.133 mmol) to acid 2.1 (0.6 g, 2.66 mmol), (COCl) at room temperature 2 (0.466 mL, 5.32 mmol) of CH 2 Cl 2 (10.6mL) in suspension. The mixture was stirred at room temperature for 6 hours, then concentrated under reduced pressure to afford the acid chloride 2.2.
[0189] step 2
[0190] A solution of acid chloride 2.2 (649 mg, 2.66 mmol) in dioxane (1.5 mL) was added to ice-cold NH 4 OH solution (1.60 mL, 23.9 mmol). The mixture was stirred at 0°C for 45 minutes. The mixture was diluted with water (50 mL), and EtOAc (100 mL) was added. separate phases. The organic layer was washed with water (2x), brine (25 mL), dried (Na 2 SO 4 ), concentrated by filtration under reduced pressure to give amide 2.3; MS: m / z=225.2 (MH + ); 1 H NMR (500MHz, DMSO-d 6 ) δppm 7.95 (br.s., 1H), 8.17 (br.s., 1H), 8.39 (dd, J=2.52, 0.63Hz, 1H), 8.91 (dd, J=2.52, 0.63Hz...
Embodiment 3
[0193] Example 3: Preparation of Intermediate 3.5 (Procedure A3)
[0194]
[0195] step 1
[0196] (COCl) at room temperature 2 (1.28mL, 14.6mmol) was added to acid 3.1 (1.00g, 7.29mmol) in CH 2 Cl 2 (29mL) suspension. The mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure to afford the acid chloride 3.2. The compound was used directly in the next reaction.
[0197] step 2
[0198] will cold NH 4 OH solution (4.86 mL, 72.9 mmol) was quickly added to an ice-cold suspension of acid chloride 3.2 (1.13 g, 7.29 mmol) in a mixture of dioxane (10 mL) and THF (10 mL). The mixture was stirred at 0°C for 45 minutes. The crude mixture was diluted with water and extracted with EtOAc (3x). The aqueous layer was saturated with solid NaCl and re-extracted with EtOAc (2x). The combined organic layers were washed with brine, dried (Na 2 SO 4 ), concentrated by filtration under reduced pressure to give amide 3.3; MS:...
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