Ethyl Acetate → HCID 178460286, compound

HRID 577709Notes

Reaction equation

[NH2:1][C@H:2]1[CH2:5][C@H:4]([O:6][C:7]2[C:8]3[C:22]([C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=4)=[CH:21][N:20]([CH2:29][OH:30])[C:9]=3[N:10]=[C:11]([NH:13][C:14]3[CH:15]=[N:16][N:17]([CH3:19])[CH:18]=3)[N:12]=2)[CH2:3]1.[C:31](=[O:34])(O)[O-].[Na+].[C:36](OCC)(=O)[CH3:37]>>[OH:30][CH2:29][N:20]1[C:9]2[N:10]=[C:11]([NH:13][C:14]3[CH:15]=[N:16][N:17]([CH3:19])[CH:18]=3)[N:12]=[C:7]([O:6][C@H:4]3[CH2:3][C@H:2]([NH:1][C:31](=[O:34])[CH:36]=[CH2:37])[CH2:5]3)[C:8]=2[C:22]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=2)=[CH:21]1

Participants

Reactant 3

HCID 8857Ethyl Acetate

HCID 516892Sodium Bicarbonate

HCID 178480797HCID 178480797, compound

Product 1

HCID 178460286HCID 178460286, compound

Procedure

To a solution of {4-[(trans-3-aminocyclobutyl)oxy]-2-[(1-methyl-1H-pyrazol-4-yl)amino]-5-(pyridin-2-yl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl}methanol in ethyl acetate (5 mL) was added saturated aqueous sodium bicarbonate (5 mL) and stirred at ambient temperature for 15 min and then added acroyl chloride (53.6 mg, 0.592 mmol) and stirred at ambient temperature for 2 hours. The volatiles were removed to give N-(trans-3-{[7-(hydroxymethyl)-2-[(1-methyl-1H-pyrazol-4-yl)amino]-5-(pyridin-2-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]oxy}cyclobutyl)prop-2-enamide. Ethanol (10 mL) was then added to the residue, followed by potassium carbonate until the pH of the reaction mixture was about 12. The reaction mixture was then stirred at ambient temperature for 2 hrs. The solid was then removed and the volatiles were concentrated down in vacuo and purified by preparative SFC method using a Zymor, Inc. Pyr/Diol, 150×21.2 mm, 5 μm column using the ethanol/CO2 with flow rate 50.0 mL/min using gradient 20%-40% ethanol ramp at 4%/min, hold 40% ethanol for 0.5 min which was then lyophilized to afford the title compound (18.8 mg, 7.4% yield) as a white solid. 1H NMR (700 MHz, DMSO) δ ppm 11.41-11.96 (m, 1H) 8.88-9.01 (m, 1H) 8.57-8.63 (m, 1H) 8.52-8.55 (m, 1H) 8.10-8.15 (m, 1H) 7.87-7.93 (m, 1H) 7.80-7.85 (m, 1H) 7.47-7.55 (m, 2H) 7.18-7.24 (m, 1H) 6.21-6.32 (m, 1H) 6.09-6.15 (m, 1H) 5.61-5.67 (m, 1H) 5.52-5.60 (m, 1H) 4.42-4.52 (m, 1H) 3.78-3.86 (m, 3H) 2.52-2.56 (m, 4H). m/z (ESI+) for C22H22N8O2 431.1 (M+H)+.

Workup

customThe volatiles were removed

Sources & evidence

ORD record: ord-2893a479ce574c1eaa71c3c03fa88413
Source dataset: uspto-grants-2015_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09040547B2

Reaction notes

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