Diisopropylethylamine → (2S,4R)-2-(3-Bromo-5-methoxycarbonyl-phenylcarbamoyl)-4-fluoro-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 1527357

반응식

HRID 1527357 반응식
[C:1]([N:8]1[CH2:15][C@H:14]([F:16])[CH2:13][C@H:9]1[C:10]([OH:12])=O)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[NH2:17][C:18]1[CH:19]=[C:20]([CH:25]=[C:26]([Br:28])[CH:27]=1)[C:21]([O:23][CH3:24])=[O:22].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C.O>[C:4]([O:3][C:1]([N:8]1[CH2:15][C@H:14]([F:16])[CH2:13][C@H:9]1[C:10](=[O:12])[NH:17][C:18]1[CH:19]=[C:20]([C:21]([O:23][CH3:24])=[O:22])[CH:25]=[C:26]([Br:28])[CH:27]=1)=[O:2])([CH3:5])([CH3:6])[CH3:7]

참가 물질

7

반응물 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 12043048(2S,4R)-1-[(tert-butoxy)carbonyl]-4-fluoropyrrolidine-2-carboxylic acidHCID 18763420Methyl 3-amino-5-bromobenzoate

생성물 1

HCID 68284215(2S,4R)-2-(3-Bromo-5-methoxycarbonyl-phenylcarbamoyl)-4-fluoro-pyrrolidine-1-carboxylic acid tert-butyl ester

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매

실험 절차

To a mixture of N-Boc-trans-4-fluoro-L-proline (500 mg, 2.14 mmol), methyl 3-amino-5-bromobenzoate (592 mg, 2.57 mmol) and HBTU (1.22 g, 3.22 mmol) in DMF (6 mL) was added DIPEA (734 μl, 4.29 mmol) and the resulting solution was stirred at RT under nitrogen overnight. The mixture was poured into water and extracted three times with EtOAc. The combined organic layers were washed twice with water, dried over Na2SO4, filtered and concentrated. The crude residue was purified by flash column chromatography on silica gel (c-hexane 100% to c-hexane/EtOAc 70:30) to give the desired material. TLC, Rf (c-hexane/EtOAc 1:2)=0.8; MS (LC/MS): 467.0/469.0 [M+Na]+, 345.1/347.0 [MH−Boc]+, 443.1/445.1 [M−H]−; tR (HPLC conditions a): 3.77 min.

후처리

  1. extractionextracted three times with EtOAc
  2. washThe combined organic layers were washed twice with water
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude residue was purified by flash column chromatography on silica gel (c-hexane 100% to c-hexane/EtOAc 70:30)

출처 및 근거

ORD 기록
ord-3498159953664b65a899ca61b1996877
출처 데이터셋
uspto-grants-2015_07
특허 번호
US09085555B2

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