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

HRID 2196504
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HRID 2196504 반응식
[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]
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참가 물질

7

반응물 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

생성물 1

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

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매

실험 절차

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)+

후처리

  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

출처 및 근거

ORD 기록
ord-5a145b044f3c454c88bf6746cf091379
출처 데이터셋
uspto-grants-2012_12
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08338437B2

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