Sodium borohydride → 1-(2-(5-chloro-4-(5-cyclopropyl-1H-pyrazol-3-ylamino)pyrimidin-2-yl)-4-methylthiazol-5-yl)ethanol

HRID 1484994Notes

Reaction equation

HRID 1484994 reaction equation
[BH4-].[Na+].[Cl:3][C:4]1[C:5]([NH:19][C:20]2[CH:24]=[C:23]([CH:25]3[CH2:27][CH2:26]3)[NH:22][N:21]=2)=[N:6][C:7]([C:10]2[S:11][C:12]([C:16](=[O:18])[CH3:17])=[C:13]([CH3:15])[N:14]=2)=[N:8][CH:9]=1>C1COCC1.CO>[Cl:3][C:4]1[C:5]([NH:19][C:20]2[CH:24]=[C:23]([CH:25]3[CH2:27][CH2:26]3)[NH:22][N:21]=2)=[N:6][C:7]([C:10]2[S:11][C:12]([CH:16]([OH:18])[CH3:17])=[C:13]([CH3:15])[N:14]=2)=[N:8][CH:9]=1

Participants

5

Reactant 2

HCID 4311764Sodium borohydrideHCID 581693681-(2-(5-Chloro-4-(5-cyclopropyl-1H-pyrazol-3-ylamino)pyrimidin-2-yl)-4-methylthiazol-5-yl)ethanone2×

Product 1

HCID 581695071-(2-(5-chloro-4-(5-cyclopropyl-1H-pyrazol-3-ylamino)pyrimidin-2-yl)-4-methylthiazol-5-yl)ethanolYield 80%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

NaBH4 (46 mg, 1.2 mmol, 3.0 equiv.) was added to a solution of 1-(2-(5-Chloro-4-(5-cyclopropyl-1H-pyrazol-3-ylamino)pyrimidin-2-yl)-4-methylthiazol-5-yl)ethanone (Compound 297 (150 mg, 0.4 mmol, 1.0 equiv.) in THF (2 mL) and methanol (2 mL) at rt. The mixture was stirred for 0.5 h, then, concentrated. The residue was partitioned between ethyl acetate and water. The organic layer was dried and concentrated. The residue was recrystallized with methanol and isopropyl ether to afford 1-(2-(5-chloro-4-(5-cyclopropyl-1H-pyrazol-3-ylamino)pyrimidin-2-yl)-4-methylthiazol-5-yl)ethanol (Compound 296) (120 mg, 80%). LC-MS (m/z)=377.0 [M+H]+. 1H NMR (400 MHz, DMSO-d6): δ 0.70-0.78 (m, 2H), 0.95-1.03 (m, 2H), 1.41 (d, J=5.2 Hz, 3H), 1.89-1.96 (m, 1H), 2.38 (s, 3H), 5.04-5.08 (m, 1H), 5.75 (d, J=2.8 Hz, 1H), 6.62 (s, 1H), 8.47 (s, 1H), 9.51 (s, 1H), 12.33 (s, 1H).

Workup

  1. concentrationconcentrated
  2. customThe residue was partitioned between ethyl acetate and water
  3. customThe organic layer was dried
  4. concentrationconcentrated
  5. customThe residue was recrystallized with methanol and isopropyl ether

Sources & evidence

ORD record
ord-a360d1a126344e87bb11703f6af01b96
Source dataset
uspto-grants-2016_08
Patent number
US09422271B2

Reaction notes

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