Triethylamine → HCID 178522184, compound

HRID 1509874Notes

Reaction equation

HRID 1509874 reaction equation
Cl.[N:2]1([C:9]2[CH:14]=[CH:13][C:12]([NH:15][C:16]([C:18]3[N:19]=[C:20]([C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=4)[O:21][C:22]=3[C:23]([F:26])([F:25])[F:24])=[O:17])=[CH:11][CH:10]=2)[CH2:8][CH2:7][CH2:6][NH:5][CH2:4][CH2:3]1.[CH2:33]([O:40][C:41]([C@H:43]1[CH2:48][CH2:47][C@@H:46]([C:49](O)=[O:50])[CH2:45][CH2:44]1)=[O:42])[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1.C(N(CC)CC)C.C1CN([P+](Br)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F>CN(C=O)C>[CH2:33]([O:40][C:41]([C@H:43]1[CH2:48][CH2:47][C@@H:46]([C:49]([N:5]2[CH2:6][CH2:7][CH2:8][N:2]([C:9]3[CH:14]=[CH:13][C:12]([NH:15][C:16]([C:18]4[N:19]=[C:20]([C:27]5[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=5)[O:21][C:22]=4[C:23]([F:26])([F:24])[F:25])=[O:17])=[CH:11][CH:10]=3)[CH2:3][CH2:4]2)=[O:50])[CH2:45][CH2:44]1)=[O:42])[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 2733179PyBroPHCID 866388652-Phenyl-5-trifluoromethyl-oxazole-4-carboxylic acid (4-[1,4]diazepan-1-yl-phenyl)-amide hydrochlorideHCID 178525734HCID 178525734, compound

Product 1

HCID 178522184HCID 178522184, compoundYield 71%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 2-phenyl-5-trifluoromethyl-oxazole-4-carboxylic acid (4-[1,4]diazepan-1-yl-phenyl)-amide hydrochloride (100 mg, 0.21 mmol), cis-cyclohexane-1,4-dicarboxylic acid monobenzyl ester (0.67 mg, 0.25 mmol), and triethyl amine (0.070 mL) in DMF (5 mL) was stirred for 5 minutes and PyBroP (116 mg, 0.25 mmol) was added. The mixture was stirred at room temperature and after 1.0 hr the reaction was concentrated to dryness. The residue was extracted with ethyl acetate and washed with saturated ammonium chloride (100 mL), water (50 mL), brine (100 mL) and dried with anhydrous sodium sulfate. The solvent was removed and the crude material was purified on a flash column chromatography eluted with ethyl acetate/hexanes to afford cis-4-(4-{4-[(2-phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-phenyl}-[1,4]diazepane-1-carbonyl)-cyclohexanecarboxylic acid benzyl ester (100 mg, 71% yield) as a white solid. LCMS for C37H37F3N4O5 calcd. (m/e) 674, observed 675 (M+H).

Workup

  1. stirringThe mixture was stirred at room temperature and after 1.0 hr the reaction
  2. concentrationwas concentrated to dryness
  3. extractionThe residue was extracted with ethyl acetate
  4. washwashed with saturated ammonium chloride (100 mL), water (50 mL), brine (100 mL)
  5. dry with materialdried with anhydrous sodium sulfate
  6. customThe solvent was removed
  7. customthe crude material was purified on a flash column chromatography
  8. washeluted with ethyl acetate/hexanes

Sources & evidence

ORD record
ord-cd890b0dc7664d358cff9d301038d322
Source dataset
uspto-grants-2012_07
Patent number
US08211884B2

Reaction notes

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