Sodium Hydroxide → HCID 178435043, compound

HRID 2306778Notes

Reaction equation

HRID 2306778 reaction equation
[CH3:1][C:2]1[S:6][C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)=[N:4][C:3]=1[CH2:13][NH:14][C@H:15]1[CH2:20][CH2:19][C@H:18]([C:21]2[CH:30]=[CH:29][C:24]3[NH:25][C:26](=[O:28])[O:27][C:23]=3[CH:22]=2)[CH2:17][CH2:16]1.[OH-].[Na+].[BH-](OC(C)=O)(OC(C)=O)O[C:35](C)=O.[Na+]>CO>[CH3:35][N:14]([CH2:13][C:3]1[N:4]=[C:5]([C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=2)[S:6][C:2]=1[CH3:1])[C@H:15]1[CH2:20][CH2:19][C@H:18]([C:21]2[CH:30]=[CH:29][C:24]3[NH:25][C:26](=[O:28])[O:27][C:23]=3[CH:22]=2)[CH2:17][CH2:16]1

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 5049666Sodium triacetoxyborohydrideHCID 178435044HCID 178435044, compound2×

Product 1

HCID 178435043HCID 178435043, compoundYield 71%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of trans-6-{4-[(5-methyl-2-phenyl-thiazol-4-ylmethyl)-amino]-cyclohexyl}-3H-benzoxazol-2-one of formula 42 (510 mg, 1.12 mmol), 2N NaOH (1 mL), and p-formaldehyde (168 mg, 5.60 mmol) in MeOH (10 mL) was stirred for 3 hours, NaBH(OAc)3 (332 mg, 1,56 mmol) was added, and the mixture was stirred overnight. The reaction was quenched by addition of MeOH. Concentration under reduced pressure followed by purification by flash chromatography (silica gel, 95:5:1 CH2Cl2:MeOH:NH4OH) gave trans-6-{4-[methyl-(5-methyl-2-phenyl-thiazol-4-ylmethyl)-amino]-cyclohexyl}-3H-benzoxazol-2-one (43) (345 mg, 71%), as a white solid: mp 246-248° C.; IR (KBr): 2927, 1773 cm−1: 1H NMR (500 MHz, DMSO-d6) δ 7.88 (dd, J=8, 2 Hz, 1H), 7.44 (m, 5H), 7.15 (s, 1H), 6.98 (m, 1H), 3.75 (s, 2H), 2.53 (m, 1H), 2.48 (m, 1H), 2.48 (s, 3H), 2.24 (s, 3H), 1.86 (m, 4H), 1.47 (m, 4H); CI-MS (methane) (m/z): 434 [M+H]+; HRMS-API (m/z): [M+H]+ calcd for C25H27N3O2S, 434.1902; found, 434.1903; HPLC: method A, 12.46 minutes (99.0%); method B, 14.05 minutes (98.7%); Anal. Calcd for C25H27N3O2S.0.25H2O: C, 68.54; H, 6.33; N, 9.59. Found: C, 68.21; H, 6.07; N, 9.59.

Workup

  1. stirringthe mixture was stirred overnight
  2. customThe reaction was quenched by addition of MeOH
  3. concentrationConcentration under reduced pressure
  4. customfollowed by purification by flash chromatography (silica gel, 95:5:1 CH2Cl2:MeOH:NH4OH)

Sources & evidence

ORD record
ord-e0444ab5b9d54dbda74c0680cf50f0bd
Source dataset
uspto-grants-2004_12
Patent number
US06828341B2

Reaction notes

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