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

HRID 509565ノート

反応式

HRID 509565 の反応式
[F:1][C:2]1[C:7]2[C:8]([C:18](=[O:21])[NH:19][CH3:20])=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[O:10][C:6]=2[CH:5]=[CH:4][C:3]=1[C:22]1[C:23]([CH3:33])=[CH:24][C:25]([O:31][CH3:32])=[C:26]([CH:30]=1)[C:27](O)=[O:28].Cl.[NH2:35][C:36]1([C:47]2[N:52]=[CH:51][CH:50]=[CH:49][N:48]=2)[CH2:39][N:38]([C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])[CH2:37]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[C:7]2[C:8]([C:18](=[O:21])[NH:19][CH3:20])=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[O:10][C:6]=2[CH:5]=[CH:4][C:3]=1[C:22]1[C:23]([CH3:33])=[CH:24][C:25]([O:31][CH3:32])=[C:26]([CH:30]=1)[C:27]([NH:35][C:36]1([C:47]2[N:48]=[CH:49][CH:50]=[CH:51][N:52]=2)[CH2:37][N:38]([C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])[CH2:39]1)=[O:28]

参加物

7

反応物 4

HCID 8471TriethylamineHCID 2724699PyBOPHCID 592754645-(4-Fluoro-2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl) 2-methoxy-4-methylbenzoic acidHCID 89825528Tert-butyl 3-amino-3-(pyrimidin-2-yl)azetidine-1-carboxylate hydrochloride

生成物 1

HCID 89825398Tert-butyl 3-(5-(4-fluoro-2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl)-2-methoxy-4-methylbenzamido)-3-(pyrimidin-2-yl)azetidine-1-carboxylate

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

実験手順

To a mixture of 5-(4-fluoro-2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl)-2-methoxy-4-methylbenzoic acid (50 mg, 0.111 mmol) and tert-butyl 3-amino-3-(pyrimidin-2-yl)azetidine-1-carboxylate hydrochloride (31.8 mg, 0.111 mmol) in DMF (1 ml) in a 25 ml round-bottomed flask was added PyBOP (69.2 mg, 0.133 mmol) and then triethylamine (0.046 ml, 0.332 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-(5-(4-fluoro-2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl)-2-methoxy-4-methylbenzamido)-3-(pyrimidin-2-yl)azetidine-1-carboxylate. Yield: 40 mg (53%). LCMS: (ES+) m/z observed=584.2 (M+H)+ of 4-fluoro-2-(4-fluorophenyl)-5-(4-methoxy-2-methyl-5-(3-(pyrimidin-2-yl)azetidin-3-ylcarbamoyl)phenyl)-N-methylbenzofuran-3-carboxamide

後処理

  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)

出典と根拠

ORDレコード
ord-e5e5305aa1ae4d6fa1e3297750fc136a
出典データセット
uspto-grants-2015_08
特許番号
US09096580B2

反応ノート

読み込み中…