Sodium borohydride → HCID 70984390, compound

HRID 928148Notes

Reaction equation

HRID 928148 reaction equation
FC(F)(F)C([O-])=O.[CH3:8][C:9]1([CH3:41])[CH2:14][C:13](=[O:15])[CH2:12][CH2:11][CH:10]1[C:16]([C:18]1[S:19][C:20]([C:23]2[CH:24]=[C:25]([NH2+:30][C:31]3[N:36]=[C:35]([C:37]([F:40])([F:39])[F:38])[CH:34]=[CH:33][N:32]=3)[CH:26]=[C:27]([CH3:29])[CH:28]=2)=[CH:21][N:22]=1)=[O:17].[BH4-].[Na+]>CO>[OH:17][CH:16]([C:18]1[S:19][C:20]([C:23]2[CH:24]=[C:25]([NH:30][C:31]3[N:36]=[C:35]([C:37]([F:39])([F:40])[F:38])[CH:34]=[CH:33][N:32]=3)[CH:26]=[C:27]([CH3:29])[CH:28]=2)=[CH:21][N:22]=1)[CH:10]1[CH2:11][CH2:12][CH:13]([OH:15])[CH2:14][C:9]1([CH3:8])[CH3:41]

Participants

4

Reactant 2

HCID 4311764Sodium borohydrideHCID 86720199HCID 86720199, compound

Product 1

HCID 70984390HCID 70984390, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

N-(3-{2-[(2,2-Dimethyl-4-oxocyclohexyl)carbonyl]-1,3-thiazol-5-yl}-5-methylphenyl)-4-(trifluoromethyl)pyrimidin-2-aminium trifluoroacetate (100 mg, 0.166 mmol) was dissolved in methanol (1.66 mL) and cooled to 0° C. Sodium borohydride (18.8 mg, 0.498 mmol) was added to the reaction, and the resultant mixture was aged at 0° C. for 30 minutes. The reaction was quenched with water and extracted with EtOAc (3×). The combined organic layers were concentrated in vacuo and purified via silica gel column chromatography to provide 4-{hydroxy[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]methyl}-3,3-dimethylcyclohexanol. MS ESI calc'd. for C24H28F3N4O2S [M+H]+ 493. found 493. Mixture present as a ˜4:1 mixture of diastereomers. 1H NMR data reported as the observed integrals for each peak. 1H NMR (500 MHz, CDCl3) δ 8.62 (d, J=4.9, 1H), 7.77 (m, 2H), 7.62 (m, 1H), 7.28 (m, 1H), 7.04-7.00 (m, 2H), 5.07 (d, J=7.2, 0.8H), 4.94 (d, J=7.2, 0.2H), 3.98-3.91 (m, 0.8H), 3.72-3.64 (m, 0.2H), 2.34 (m, 3H), 1.77-1.20 (m, 6H), 1.21 (s, 0.6H), 1.16 (s, 2.4H), 1.12 (s, 2.4H), 0.95 (s, 0.6H). rhSyk activity=+++.

Workup

  1. customThe reaction was quenched with water
  2. extractionextracted with EtOAc (3×)
  3. concentrationThe combined organic layers were concentrated in vacuo
  4. custompurified via silica gel column chromatography

Sources & evidence

ORD record
ord-4d6c806650ef4eb58d7f30438550e553
Source dataset
uspto-grants-2016_03
Patent number
US09290490B2

Reaction notes

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