Triethylamine → (S)-methyl 2-((1-(5-((2-(tert-butoxycarbonylamino)propanamido)methyl)thiophen-3-yl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxamido)methyl)benzoate

HRID 2196504Notes

Reaction equation

HRID 2196504 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH3:31])[C:10]([NH:12][CH2:13][C:14]1[S:18][CH:17]=[C:16]([N:19]2[C:23]([C:24](O)=[O:25])=[CH:22][C:21]([C:27]([F:30])([F:29])[F:28])=[N:20]2)[CH:15]=1)=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.[NH2:33][CH2:34][C:35]1[CH:44]=[CH:43][CH:42]=[CH:41][C:36]=1[C:37]([O:39][CH3:40])=[O:38].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.C(N(CC)CC)C>CN(C=O)C.O>[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH3:31])[C:10]([NH:12][CH2:13][C:14]1[S:18][CH:17]=[C:16]([N:19]2[C:23]([C:24]([NH:33][CH2:34][C:35]3[CH:44]=[CH:43][CH:42]=[CH:41][C:36]=3[C:37]([O:39][CH3:40])=[O:38])=[O:25])=[CH:22][C:21]([C:27]([F:30])([F:28])[F:29])=[N:20]2)[CH:15]=1)=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 27609432-Carbomethoxybenzylamine hydrochlorideHCID 69298555(S)-1-(5-((2-(tert-butoxycarbonylamino)propanamido)methyl)thiophen-3-yl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxylic acid

Product 1

HCID 69300597(S)-methyl 2-((1-(5-((2-(tert-butoxycarbonylamino)propanamido)methyl)thiophen-3-yl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxamido)methyl)benzoateYield 61.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of acid 7 (preparation described in scheme 2, example 1c, step 7) (140 mg, 0.303 mmol), methyl 2-(aminomethyl)benzoate hydrochloride (61.0 mg, 0.303 mmol), BOP (134 mg, 0.303 mmol) and triethylamine (0.127 mL, 0.908 mmol) in DMF (2 mL) was shaken for 16 hours at room temperature. It was then diluted with water (˜30 mL) and extracted into ethyl acetate (3×). The ethyl acetate was combined and washed with saturated NaHCO3, brine, dried over Na2SO4, filtered and concentrated. The crude was purified by silica gel chromatography using a 25S Biotage column with a gradient of 40-65% ethyl acetate in hexanes to give compound 15f (112.7 mg, 61.1% yield) as a white crusty solid. LRMS (ESI): calc. 609.2; found 632.1 (MNa)+

Workup

  1. extractionextracted into ethyl acetate (3×)
  2. washwashed with saturated NaHCO3, brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude was purified by silica gel chromatography

Sources & evidence

ORD record
ord-5a145b044f3c454c88bf6746cf091379
Source dataset
uspto-grants-2012_12
Patent number
US08338437B2

Reaction notes

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