Sodium Bicarbonate → HCID 71727583, compound

HRID 1774223Notes

Reaction equation

HRID 1774223 reaction equation
Cl.CO.[Si]([O:11][CH:12]([CH3:43])[CH2:13][CH:14]([N:23]1[CH:28]=[CH:27][C:26]([C:29]2[CH:34]=[CH:33][N:32]=[C:31]([NH:35][CH:36]3[CH2:41][CH2:40][O:39][CH2:38][CH2:37]3)[N:30]=2)=[CH:25][C:24]1=[O:42])[C:15]1[CH:20]=[CH:19][C:18]([Cl:21])=[C:17]([F:22])[CH:16]=1)(C(C)(C)C)(C)C.C([O-])(O)=O.[Na+]>CO>[Cl:21][C:18]1[CH:19]=[CH:20][C:15]([CH:14]([N:23]2[CH:28]=[CH:27][C:26]([C:29]3[CH:34]=[CH:33][N:32]=[C:31]([NH:35][CH:36]4[CH2:41][CH2:40][O:39][CH2:38][CH2:37]4)[N:30]=3)=[CH:25][C:24]2=[O:42])[CH2:13][CH:12]([OH:11])[CH3:43])=[CH:16][C:17]=1[F:22]

Participants

5

Reactant 3

HCID 516892Sodium BicarbonateHCID 21893726Hydrochloride methanolHCID 86696724HCID 86696724, compound

Product 1

HCID 71727583HCID 71727583, compoundYield 50%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

HCl/methanol (3N, 1.0 mL) was added at 5° C. to a solution of 1-(3-(tert-butyldimethylsilyloxy)-1-(4-chloro-3-fluorophenyl)butyl)-4-(2-((tetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)pyridin-2(1H)-one (90.0 mg, 0.154 mmol) in methanol (3.0 mL). After being stirred at room temperature for 2 hours, the reaction mixture was adjusted to pH around 8-9 with saturated NaHCO3, extracted with dichloromethane, dried over Na2SO4 and concentrated. The residue was purified with prep-HPLC to afford 1-(1-(4-chloro-3-fluorophenyl)-3-hydroxybutyl)-4-(2-((tetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)pyridin-2(1H)-one (36 mg, 50% yield) as a solid. 1H NMR (500 MHz, (CD3)2SO) δ 10.92 (s, 1H), 8.41 (d, J=5.0 Hz, 1H), 7.95 (m, 1H), 7.58 (m, 1H), 7.46 (m, 1H), 7.30 (m, 1H), 7.23 (m, 1H), 7.10 (m, 1H), 7.07 (m, 1H), 6.87 (m, 1H), 6.14 (m, 1H), 4.70 (m, 1H), 3.97 (m, 1H), 3.89-3.87 (m, 2H), 3.41-3.33 (m, 2H), 2.47 (m, 1H), 2.06 (m, 1H), 1.86-1.84 (m, 2H), 1.56-1.52 (m, 2H), 1.12-1.09 (m, 3H); LCMS (ESI) m/z: 473.2 [M+H]+.

Workup

  1. extractionextracted with dichloromethane
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated
  4. customThe residue was purified with prep-HPLC

Sources & evidence

ORD record
ord-d1e401dfe06d486289aa9431fb5332fd
Source dataset
uspto-grants-2016_02
Patent number
US09259470B2

Reaction notes

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