Ammonium Chloride → (3-Carbamoyl-5-chloro-indol-1-yl)-acetic acid tert-butyl ester

HRID 1527212노트

반응식

HRID 1527212 반응식
[C:1]([O:5][C:6]([CH2:8][N:9]1[C:17]2[C:12](=[CH:13][C:14]([Cl:18])=[CH:15][CH:16]=2)[C:11]([C:19]([OH:21])=O)=[CH:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH4+].[Cl-].C[N:25](C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>C(Cl)Cl>[C:1]([O:5][C:6](=[O:7])[CH2:8][N:9]1[C:17]2[C:12](=[CH:13][C:14]([Cl:18])=[CH:15][CH:16]=2)[C:11]([C:19](=[O:21])[NH2:25])=[CH:10]1)([CH3:4])([CH3:3])[CH3:2]

참가 물질

6

반응물 4

HCID 25517Ammonium Chloride2회HCID 81531Diisopropylethylamine2회HCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 682837821-tert-Butoxycarbonylmethyl-5-chloro-1H-indole-3-carboxylic acid

생성물 1

HCID 68283031(3-Carbamoyl-5-chloro-indol-1-yl)-acetic acid tert-butyl ester

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

To a mixture of 1-tert-butoxycarbonylmethyl-5-chloro-1H-indole-3-carboxylic acid (400 mg, 1.29 mmol) in CH2Cl2 (6 mL) were added successively NH4Cl (138 mg, 2.58 mmol), HBTU (1.22 g, 3.23 mmol) and DIPEA (0.902 mL, 5.17 mmol). Stirring was continued at RT for 16 h. Additional aliquots of NH4Cl (2 equiv) and DIPEA (4 equiv) were added to the reaction mixture. After stirring for 4 h, the reaction mixture was diluted with CH2Cl2 and the solution was washed with water (2×), 0.1N aqueous HCl (2×), saturated aqueous NaHCO3 (2×) and brine, dried (Phase separator) and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel (EtOAc/c-hexane gradient 2:1 to 1:0) to give the title compound as a white solid. TLC Rf (EtOAc/c-hexane 2:1)=0.20; MS (LC/MS): 309 [M+H]+, 617 [2M+H]+; tR (HPLC conditions b): 4.75 min.

후처리

  1. stirringAfter stirring for 4 h
  2. washthe solution was washed with water (2×), 0.1N aqueous HCl (2×), saturated aqueous NaHCO3 (2×) and brine
  3. customdried (Phase separator)
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by flash column chromatography on silica gel (EtOAc/c-hexane gradient 2:1 to 1:0)

출처 및 근거

ORD 기록
ord-763d57ed96a64c9fb2b6da2f0dd59682
출처 데이터셋
uspto-grants-2015_07
특허 번호
US09085555B2

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