Water → HCID 86696696, compound

HRID 1774195Notes

Reaction equation

HRID 1774195 reaction equation
[CH3:1][C:2]1[CH:7]=[C:6]([NH2:8])[CH:5]=[CH:4][N:3]=1.[Li]C(C)(C)C.[Si:14]([O:21][CH2:22][C@@H:23]([N:32]1[CH:37]=[CH:36][C:35]([C:38]2[CH:43]=[CH:42][N:41]=[C:40](S(C)(=O)=O)[N:39]=2)=[CH:34][C:33]1=[O:48])[C:24]1[CH:29]=[CH:28][C:27]([Cl:30])=[C:26]([F:31])[CH:25]=1)([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15].O>C1COCC1>[Si:14]([O:21][CH2:22][C@@H:23]([N:32]1[CH:37]=[CH:36][C:35]([C:38]2[CH:43]=[CH:42][N:41]=[C:40]([NH:8][C:6]3[CH:5]=[CH:4][N:3]=[C:2]([CH3:1])[CH:7]=3)[N:39]=2)=[CH:34][C:33]1=[O:48])[C:24]1[CH:29]=[CH:28][C:27]([Cl:30])=[C:26]([F:31])[CH:25]=1)([C:17]([CH3:20])([CH3:18])[CH3:19])([CH3:16])[CH3:15]

Participants

6

Reactant 4

HCID 962WaterHCID 7286704-Amino-2-methylpyridineHCID 71727006HCID 71727006, compoundHCID 178418306HCID 178418306, compound

Product 1

HCID 86696696HCID 86696696, compoundYield 38%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

2-Methylpyridin-4-amine (0.28 g, 2.6 mmol) was placed in THF (5 mL) and cooled to −78° C. t-BuLi (1.5 mL, 2.6 mmol) was added dropwise, and the solution was warmed to 0° C. for 30 minutes. This solution was then added dropwise to a −78° C. THF solution (5 mL) of (S)-1-(2-(tert-butyldimethylsilyloxy)-1-(4-chloro-3-fluorophenyl)ethyl)-4-(2-(methylsulfonyl)pyrimidin-4-yl)pyridin-2(1H)-one (0.070 g, 0.13 mmol). The reaction was stirred for an additional 30 minutes at −78° C., then poured into water, and extracted with DCM. The combined organic fractions were dried (MgSO4), filtered, and concentrated to give the crude product, which was purified by column chromatography (500:10-500:20 DCM/MeOH) to give the product (S)-1-(2-(tert-butyldimethylsilyloxy)-1-(4-chloro-3-fluorophenyl)ethyl)-4-(2-((2-methylpyridin-4-yl)amino)pyrimidin-4-yl)pyridin-2(1H)-one (0.028 g, 38% yield).

Workup

  1. additionwas added dropwise
  2. additionThis solution was then added dropwise to a −78° C
  3. extractionextracted with DCM
  4. dry with materialThe combined organic fractions were dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give the crude product, which
  8. customwas purified by column chromatography (500:10-500:20 DCM/MeOH)

Sources & evidence

ORD record
ord-ff2b0e717d8046a696253cca7eaa3580
Source dataset
uspto-grants-2016_02
Patent number
US09259470B2

Reaction notes

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