Triethylamine → Tert-butyl 3-(3-fluoro-5-(4-fluoro-2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl)-4-methylbenzamido)-3-(pyrimidin-2-yl)azetidine-1-carboxylate

HRID 509566노트

반응식

HRID 509566 반응식
[F:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([C:12]2[CH:13]=[CH:14][C:15]3[O:19][C:18]([C:20]4[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=4)=[C:17]([C:27](=[O:30])[NH:28][CH3:29])[C:16]=3[C:31]=2[F:32])[C:10]=1[CH3:11])[C:5](O)=[O:6].Cl.[NH2:34][C:35]1([C:46]2[N:51]=[CH:50][CH:49]=[CH:48][N:47]=2)[CH2:38][N:37]([C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[CH2:36]1.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C>CN(C=O)C.O>[F:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([C:12]2[CH:13]=[CH:14][C:15]3[O:19][C:18]([C:20]4[CH:21]=[CH:22][C:23]([F:26])=[CH:24][CH:25]=4)=[C:17]([C:27](=[O:30])[NH:28][CH3:29])[C:16]=3[C:31]=2[F:32])[C:10]=1[CH3:11])[C:5]([NH:34][C:35]1([C:46]2[N:47]=[CH:48][CH:49]=[CH:50][N:51]=2)[CH2:36][N:37]([C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[CH2:38]1)=[O:6]

참가 물질

7

반응물 4

HCID 8471TriethylamineHCID 2724699PyBOPHCID 584729003-Fluoro-5-(4-fluoro-2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl)-4-methylbenzoic acidHCID 89825528Tert-butyl 3-amino-3-(pyrimidin-2-yl)azetidine-1-carboxylate hydrochloride

생성물 1

HCID 89825538Tert-butyl 3-(3-fluoro-5-(4-fluoro-2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl)-4-methylbenzamido)-3-(pyrimidin-2-yl)azetidine-1-carboxylate

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매

실험 절차

To a mixture of 3-fluoro-5-(4-fluoro-2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl)-4-methylbenzoic acid (50 mg, 0.114 mmol) and tert-butyl 3-amino-3-(pyrimidin-2-yl)azetidine-1-carboxylate hydrochloride (35.9 mg, 0.125 mmol) in DMF (1 ml) in a 25 ml round-bottomed flask was added PyBop (77 mg, 0.148 mmol) and then triethylamine (0.032 ml, 0.228 mmol). The reaction mixture was stirred overnight, and then diluted with water and extracted with EtOAc. The organic layer was further washed with water, dried over sodium sulphate and concentrated. The crude product was then purified by column chromatography (2% methanol in chloroform) to afford tert-butyl 3-(3-fluoro-5-(4-fluoro-2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl)-4-methylbenzamido)-3-(pyrimidin-2-yl)azetidine-1-carboxylate. Yield: 40 mg (52.4%). LCMS: (ES+) m/z observed=572.2 (M+H)+ of 4-fluoro-5-(3-fluoro-2-methyl-5-(3-(pyrimidin-2-yl)azetidin-3-ylcarbamoyl)phenyl)-2-(4-fluorophenyl)-N-methylbenzofuran-3-carboxamide

후처리

  1. extractionextracted with EtOAc
  2. washThe organic layer was further washed with water
  3. dry with materialdried over sodium sulphate
  4. concentrationconcentrated
  5. customThe crude product was then purified by column chromatography (2% methanol in chloroform)

출처 및 근거

ORD 기록
ord-b67bb64d53154e2ea5f05259ae09c32b
출처 데이터셋
uspto-grants-2015_08
특허 번호
US09096580B2

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