Sodium hydride → (1S,3S)-3-[3-((S)-1-Methyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-indan-1-ylamine

HRID 1402153ノート

反応式

HRID 1402153 の反応式
[NH2:1][C@@H:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C@@H:4]([OH:11])[CH2:3]1.[H-].[Na+].F[C:15]1[CH:16]=[CH:17][C:18]2[N:19]([C:21]([C@@H:24]3[CH2:28][CH2:27][CH2:26][N:25]3[CH3:29])=[N:22][N:23]=2)[CH:20]=1>CN(C=O)C.O>[CH3:29][N:25]1[CH2:26][CH2:27][CH2:28][C@H:24]1[C:21]1[N:19]2[CH:20]=[C:15]([O:11][C@@H:4]3[C:5]4[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=4)[C@@H:2]([NH2:1])[CH2:3]3)[CH:16]=[CH:17][C:18]2=[N:23][N:22]=1

参加物

6

反応物 3

HCID 24758Sodium hydrideHCID 12013033(1S,3S)-3-Amino-2,3-dihydro-1H-inden-1-olHCID 866870156-Fluoro-3-((S)-1-methyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridine

生成物 1

HCID 86687014(1S,3S)-3-[3-((S)-1-Methyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-indan-1-ylamine

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

反応条件

温度
60 °C

実験手順

(1S,3S)-3-Amino-indan-1-ol (110 mg, 0.74 mmol) was added to a suspension of NaH (60% in mineral oil, 87 mg, 2.17 mmol) in anhydrous DMF (5 mL) at RT and stirred for 20 min. Intermediate 5b (160 mg, 0.72 mmol) was then added in one portion and the mixture heated at 60° C. for 3 h. After cooling the mixture was diluted with water (20 mL) and extracted with EtOAc (3×50 mL). The combined organics were washed with brine (50 mL), dried (MgSO4) and evaporated in vacuo. The residue was purified by FCC, using 0-10% MeOH in DCM, to give the title compound as give a foam (132 mg, 52%). LCMS (Method 1): Rt 0.34 min, m/z 350 [MH+]. 1H NMR (300 MHz, CDCl3): 1.95-2.16 (6H, m), 2.24 (3H, s), 2.26-2.45 (2H, m), 2.77 (1H, ddd, J 14.1, 7.0, 2.0), 3.23-3.30 (1H, m), 4.02-4.09 (1H, m), 4.71 (1H, t, J 6.8), 5.68 (1H, dd, J 6.2, 1.9), 7.04 (1H, dd, J 9.9, 2.2), 7.29-7.50 (4H, m), 7.64 (1H, dd, J 9.9, 0.9), 8.35 (1H, d, J 2.2).

後処理

  1. temperatureAfter cooling the mixture
  2. extractionextracted with EtOAc (3×50 mL)
  3. washThe combined organics were washed with brine (50 mL)
  4. dry with materialdried (MgSO4)
  5. customevaporated in vacuo
  6. customThe residue was purified by FCC

出典と根拠

ORDレコード
ord-dfa33627bc3b4b2f8b462f8682c460dc
出典データセット
uspto-grants-2014_12
特許番号
US08907094B2

反応ノート

読み込み中…