1-methyl-1H-pyrazol-4-amine → HCID 86696674, compound

HRID 1774176Notes

Reaction equation

HRID 1774176 reaction equation
[CH3:1][N:2]1[CH:6]=[C:5]([NH2:7])[CH:4]=[N:3]1.[Si]([O:15][CH2:16][C@@H:17]([N:26]1[CH:31]=[CH:30][C:29]([C:32]2[CH:37]=[CH:36][N:35]=[C:34](S(C)(=O)=O)[N:33]=2)=[CH:28][C:27]1=[O:42])[C:18]1[CH:23]=[CH:22][C:21]([Cl:24])=[C:20]([F:25])[CH:19]=1)(C(C)(C)C)(C)C>C(O)(CC)C>[Cl:24][C:21]1[CH:22]=[CH:23][C:18]([C@H:17]([N:26]2[CH:31]=[CH:30][C:29]([C:32]3[CH:37]=[CH:36][N:35]=[C:34]([NH:7][C:5]4[CH:4]=[N:3][N:2]([CH3:1])[CH:6]=4)[N:33]=3)=[CH:28][C:27]2=[O:42])[CH2:16][OH:15])=[CH:19][C:20]=1[F:25]

Participants

4

Reactant 2

HCID 47709901-methyl-1H-pyrazol-4-amineHCID 71727006HCID 71727006, compound

Product 1

HCID 86696674HCID 86696674, compoundYield 26.8%

Reagents, catalysts & solvents 1

HCID 6568(+-)-2-ButanolSolvent

Procedure

A solution of 1-methyl-1H-pyrazol-4-amine (0.054 g, 0.56 mmol) and (S)-1-(2-(tert-butyldimethylsilyloxy)-1-(4-chloro-3-fluorophenyl)ethyl)-4-(2-(methylsulfonyl)pyrimidin-4-yl)pyridin-2(1H)-one (0.060 g, 0.11 mmol) in sec-BuOH (1 mL) was heated to 120° C. in a microwave reactor for 2 hours. The reaction mixture was cooled to room temperature and concentrated. The residue was diluted with ethyl acetate and washed with H2O (2×). The organic layer was dried, filtered and concentrated. The crude product was purified by column chromatography, eluting with DCM/MeOH (25:1) to give (S)-1-(1-(4-chloro-3-fluorophenyl)-2-hydroxyethyl)-4-(2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidin-4-yl)pyridin-2(1H)-one (0.013 g, 26%). 1H NMR (400 MHz, CD3OD) δ 8.50 (d, J=5.0 Hz, 1H), 7.96 (s, 1H), 7.85 (d, J=7.0 Hz, 1H), 7.58 (s, 1H), 7.48 (m, 1H), 7.34-7.28 (m, 2H), 7.20-7.17 (m, 2H), 7.06 (m, 1H), 6.12 (m, 1H), 4.28 (m, 1H), 4.19 (m, 1H), 3.88 (s, 3H); m/z (APCI-pos) M+1=441.1, 443.1.

Workup

  1. concentrationconcentrated
  2. additionThe residue was diluted with ethyl acetate
  3. washwashed with H2O (2×)
  4. customThe organic layer was dried
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was purified by column chromatography
  8. washeluting with DCM/MeOH (25:1)

Sources & evidence

ORD record
ord-ab4bdeb147db48138c0a30e5648699ed
Source dataset
uspto-grants-2016_02
Patent number
US09259470B2

Reaction notes

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