HCID 86696706, compound → GDC-0994

HRID 2365853Notes

Reaction equation

HRID 2365853 reaction equation
[Si]([O:8][CH2:9][C@@H:10]([N:19]1[CH:24]=[CH:23][C:22]([C:25]2[CH:30]=[CH:29][N:28]=[C:27]([NH:31][C:32]3[N:36]([CH3:37])[N:35]=[CH:34][CH:33]=3)[N:26]=2)=[CH:21][C:20]1=[O:38])[C:11]1[CH:16]=[CH:15][C:14]([Cl:17])=[C:13]([F:18])[CH:12]=1)(C(C)(C)C)(C)C>C(OCC)(=O)C>[Cl:17][C:14]1[CH:15]=[CH:16][C:11]([C@H:10]([N:19]2[CH:24]=[CH:23][C:22]([C:25]3[CH:30]=[CH:29][N:28]=[C:27]([NH:31][C:32]4[N:36]([CH3:37])[N:35]=[CH:34][CH:33]=4)[N:26]=3)=[CH:21][C:20]2=[O:38])[CH2:9][OH:8])=[CH:12][C:13]=1[F:18]

Participants

3

Reactant 1

HCID 86696706HCID 86696706, compound

Product 1

HCID 71727581GDC-0994Yield 54.6%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Procedure

Crude (S)-1-(2-((tert-butyldimethylsilyl)oxy)-1-(4-chloro-3-fluorophenyl)ethyl)-4-(2-((1-methyl-1H-pyrazol-5-yl)amino)pyrimidin-4-yl)pyridin-2(1H)-one (48 mg) was dissolved in ethyl acetate (4 mL) and treated dropwise slowly (over 2 minutes) with an ethyl acetate solution (1.0 mL, which had been saturated with HCl gas). The reaction stirred at room temperature for 15 minutes, after which time LCMS indicated complete consumption of the starting material. The reaction mixture was concentrated to an oily residue and purified by prep RP HPLC to yield (S)-1-(1-(4-chloro-3-fluorophenyl)-2-hydroxyethyl)-4-(2-((1-methyl-1H-pyrazol-5-yl)amino)pyrimidin-4-yl)pyridin-2(1H)-one (20.8 mg, 54.6% yield) as a lyophilized powder. 1H NMR (400 MHz, (CD3)2SO) δ 9.58 (s, 1H), 8.60 (d, J=5.1 Hz, 1H), 7.91 (t, J=9.0 Hz, 1H), 7.58 (t, J=8.1 Hz, 1H), 7.52-7.41 (m, 2H), 7.37 (d, J=1.8 Hz, 1H), 7.14 (dd, J=10.7, 5.1 Hz 2H), 6.86 (dd, J=7.3, 1.8 Hz, 1H), 6.27 (d, J=1.7 Hz, 1H), 5.97 (dd, J=7.7, 5.7 Hz, 1H), 5.31 (t, J=5.2 Hz, 1H), 4.15 (m, 1H), 4.10-3.95 (m, 1H), 3.69 (s, 3H); LCMS m/z 441 (M+H)+.

Workup

  1. customconsumption of the starting material
  2. concentrationThe reaction mixture was concentrated to an oily residue
  3. custompurified by prep RP HPLC

Sources & evidence

ORD record
ord-d80a49babbd3460b8f1243035e8090cb
Source dataset
uspto-grants-2014_04
Patent number
US08697715B2

Reaction notes

Loading…