Diisopropylethylamine → N-((1R,2S)-1-(1-(4-chlorophenyl)-1H-indazol-5-yloxy)-1-(3-methoxyphenyl)propan-2-yl)-2,2-difluoropropanamide

HRID 13157

反応式

HRID 13157 の反応式
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]3[C:11](=[CH:12][C:13]([O:17][C@H:18]([C:22]4[CH:27]=[CH:26][CH:25]=[C:24]([O:28][CH3:29])[CH:23]=4)[C@@H:19]([NH2:21])[CH3:20])=[CH:14][CH:15]=3)[CH:10]=[N:9]2)=[CH:4][CH:3]=1.[F:30][C:31]([F:36])([CH3:35])[C:32](O)=[O:33].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN1C(=O)CCC1.O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[C:16]3[C:11](=[CH:12][C:13]([O:17][C@H:18]([C:22]4[CH:27]=[CH:26][CH:25]=[C:24]([O:28][CH3:29])[CH:23]=4)[C@@H:19]([NH:21][C:32](=[O:33])[C:31]([F:36])([F:30])[CH3:35])[CH3:20])=[CH:14][CH:15]=3)[CH:10]=[N:9]2)=[CH:6][CH:7]=1

参加物

7

反応物 4

HCID 81531Diisopropylethylamine2 回HCID 27828252,2-Difluoropropionic acid2 回HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)2 回HCID 59339670(1R,2S)-1-(1-(4-chlorophenyl)-1H-indazol-5-yloxy)-1-(3-methoxyphenyl)propan-2-amine

生成物 1

HCID 59339651N-((1R,2S)-1-(1-(4-chlorophenyl)-1H-indazol-5-yloxy)-1-(3-methoxyphenyl)propan-2-yl)-2,2-difluoropropanamide

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 13387N-methyl-2-pyrrolidone溶媒3 回

実験手順

(1R,28)-1-(1-(4-chlorophenyl)-1H-indazol-5-yloxy)-1-(3-methoxyphenyl)propan-2-amine (126a) (256 mg, 0.63 mmol) dissolved in NMP (3.5 mL) was added to a solution of 2,2-difluoropropanoic acid (111 mg, 1.00 mmol), HATU (382 mg, 1.00 mmol) and DIPEA (0.438 mL, 2.51 mmol) in NMP (1.5 mL). The reaction mixture was stirred at r.t. for 2 h. Additional 2,2-difluoropropanoic acid (80 mg, 0.73 mmol), HATU (278 mg, 0.73 mmol) and DIPEA (0.25 mL, 1.4 mmol) in NMP (1.5 mL) was added. The reaction mixture was stirrred at r.t. for another h. Water (50 mL) was added, the mixture was extracted with EtOAc (2×50 mL), the organic phase was washed with 10% NaHSO4 (aq), brine, dried over MgSO4, filtered and evaporated to give a crude product that was purified by HPLC. The fractions containing the product was combined and freeze dried. Yield 197 mg (62%).

後処理

  1. customwas stirrred at r.t. for another h
  2. extractionthe mixture was extracted with EtOAc (2×50 mL)
  3. washthe organic phase was washed with 10% NaHSO4 (aq), brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. customevaporated

出典と根拠

ORDレコード
ord-3fe9bcf0c09d4dee8da87d8a5cf7a5e0
出典データセット
uspto-grants-2010_06
特許番号
US07728030B2

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