ホームMCPワークベンチSkills
ホームワークベンチ通知マイページ
llms.txt · MCPガイドプライバシーポリシー · 利用規約 · サポートv1.8.0
  1. ホーム
  2. /反応

Trifluoroacetic acid → 4-((3S,4S)-3-Amino-4-hydroxypyrrolidin-1-yl)-N-(4-(chlorodifluoromethoxy)phenyl)-3-(1H-pyrazol-5-yl)benzamide

HRID 525751
ノート
印刷プレビュー

反応式

HRID 525751 の反応式
O1CCCCC1[N:7]1[C:11](B2OC(C)(C)C(C)(C)O2)=[CH:10][CH:9]=[N:8]1.[NH2:21][C@@H:22]1[C@@H:26]([OH:27])[CH2:25][N:24]([C:28]2[CH:47]=[CH:46][C:31]([C:32]([NH:34][C:35]3[CH:40]=[CH:39][C:38]([O:41][C:42]([Cl:45])([F:44])[F:43])=[CH:37][CH:36]=3)=[O:33])=[CH:30][C:29]=2Br)[CH2:23]1.C([O-])([O-])=O.[Na+].[Na+].C(O)(C(F)(F)F)=O>COCCOC>[NH2:21][C@@H:22]1[C@@H:26]([OH:27])[CH2:25][N:24]([C:28]2[CH:29]=[CH:30][C:31]([C:32]([NH:34][C:35]3[CH:36]=[CH:37][C:38]([O:41][C:42]([Cl:45])([F:43])[F:44])=[CH:39][CH:40]=3)=[O:33])=[CH:46][C:47]=2[C:11]2[NH:7][N:8]=[CH:9][CH:10]=2)[CH2:23]1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

6

反応物 4

HCID 6422Trifluoroacetic acidHCID 10340Sodium CarbonateHCID 115872081-(tetrahydro-2H-pyran-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 899064294-((3 S,4S)-3-amino-4-hydroxypyrrolidin-1-yl)-3-bromo-N-(4-(chlorodifluoromethoxy)phenyl)benzamide

生成物 1

HCID 1180450264-((3S,4S)-3-Amino-4-hydroxypyrrolidin-1-yl)-N-(4-(chlorodifluoromethoxy)phenyl)-3-(1H-pyrazol-5-yl)benzamide

試薬・触媒・溶媒 1

HCID 80711,2-Dimethoxyethane溶媒

反応条件

温度
80 °C

実験手順

1-(Tetrahydro-2H-pyran-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (82 mg, 0.288 mmol) and PdCl2(dppf)-(CH2Cl2) (10.07 mg, 12 μmol) were added to a mixture of 4-((3S,4S)-3-amino-4-hydroxypyrrolidin-1-yl)-3-bromo-N-(4-(chlorodifluoromethoxy)phenyl)benzamide (Stage 76.1, 100 mg, 0.206 mmol), Na2CO3 (0.308 mL, 0.617 mmol) in DME (2 mL) under argon atmosphere and the RM was heated at 80° C. for 4 h. The RM was filtered through Hyflo® and the solvent was evaporated off under reduced pressure to give a residue which was purified by flash chromatography (Silica gel column, 12 g, DCM/EtOH from 98:2 to 8:2). The resulting intermediate was dissolved in DCM (2 mL), treated with TFA (0.198 mL, 2.57 mmol) and the RM was stirred for RT for 3 h. The solvent was evaporated off under reduced pressure and the residue was treated with sat. aq. Na2CO3, and extracted with EtOAc. The combined extracts were washed with brine (20 mL), dried over Na2SO4 and the solvent was evaporated off under reduced pressure to give the crude product which was purified by flash chromatography (Silica gel column, 12 g, DCM/MeOH from 95:5 to 7:3) and crystallized from n-hexane/DCM to give the title product as a beige solid. HPLC (Condition 7) tR=5.774 min, UPLC-MS (Condition 3) tR=0.77 min, m/z=464.2 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ ppm 2.73-2.99 (m, 2H) 3.22-3.44 (m, 3H) 3.93-4.04 (m, 1H) 5.33 (br. s, 1H) 6.39 (s, 1H) 6.74-6.94 (m, 1H) 7.31 (d, J=8.60 Hz, 2H) 7.76-8.03 (m, 4H) 10.17 (br. s, 1H).

後処理

  1. filtrationThe RM was filtered through Hyflo®
  2. customthe solvent was evaporated off under reduced pressure
  3. customto give a residue which
  4. customwas purified by flash chromatography (Silica gel column, 12 g, DCM/EtOH from 98:2 to 8:2)
  5. dissolutionThe resulting intermediate was dissolved in DCM (2 mL)
  6. customThe solvent was evaporated off under reduced pressure
  7. additionthe residue was treated with sat. aq. Na2CO3
  8. extractionextracted with EtOAc
  9. washThe combined extracts were washed with brine (20 mL)
  10. dry with materialdried over Na2SO4
  11. customthe solvent was evaporated off under reduced pressure
  12. customto give the crude product which
  13. customwas purified by flash chromatography (Silica gel column, 12 g, DCM/MeOH from 95:5 to 7:3)
  14. customcrystallized from n-hexane/DCM

出典と根拠

ORDレコード
ord-9ebbe338fe2b4dfc930b970df00bb44f
出典データセット
uspto-grants-2016_05
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09340537B2

反応ノート

読み込み中…

このページの内容参加物反応条件実験手順後処理出典と根拠反応ノート