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

Sodium Bicarbonate → 2-((3bS,4aR)-3-(difluoromethyl)-5,5-difluoro-3b,4,4a,5-tetrahydro-1H-cyclopropa[3,4]cyclopenta[1,2-c]pyrazol-1-yl)-N-((S)-2-(3,5-difluorophenyl)-1-(6-(3-hydroxy-3-methylazetidin-1-yl)-3-(1-methyl-3-(methylsulfonamido)-1H-indazol-7-yl)pyridin-2-yl)ethyl)acetamide

HRID 2170380
ノート
印刷プレビュー

反応式

HRID 2170380 の反応式
Br[C:2]1[C:3]([C@@H:14]([NH:24][C:25](=[O:41])[CH2:26][N:27]2[C:31]3[C:32]([F:37])([F:36])[C@@H:33]4[CH2:35][C@@H:34]4[C:30]=3[C:29]([CH:38]([F:40])[F:39])=[N:28]2)[CH2:15][C:16]2[CH:21]=[C:20]([F:22])[CH:19]=[C:18]([F:23])[CH:17]=2)=[N:4][C:5]([N:8]2[CH2:11][C:10]([OH:13])([CH3:12])[CH2:9]2)=[CH:6][CH:7]=1.[CH3:42][N:43]1[C:51]2[C:46](=[CH:47][CH:48]=[CH:49][C:50]=2B2OC(C)(C)C(C)(C)O2)[C:45]([NH:61][S:62]([CH3:65])(=[O:64])=[O:63])=[N:44]1.C(=O)(O)[O-].[Na+]>C1CCC(P(C2CCCCC2)C2CCCCC2)CC1.C1CCC(P(C2CCCCC2)C2CCCCC2)CC1.Cl[Pd]Cl.O1CCOCC1>[F:40][CH:38]([F:39])[C:29]1[C:30]2[C@H:34]3[CH2:35][C@H:33]3[C:32]([F:37])([F:36])[C:31]=2[N:27]([CH2:26][C:25]([NH:24][C@H:14]([C:3]2[C:2]([C:50]3[CH:49]=[CH:48][CH:47]=[C:46]4[C:51]=3[N:43]([CH3:42])[N:44]=[C:45]4[NH:61][S:62]([CH3:65])(=[O:64])=[O:63])=[CH:7][CH:6]=[C:5]([N:8]3[CH2:9][C:10]([OH:13])([CH3:12])[CH2:11]3)[N:4]=2)[CH2:15][C:16]2[CH:21]=[C:20]([F:22])[CH:19]=[C:18]([F:23])[CH:17]=2)=[O:41])[N:28]=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 3

HCID 516892Sodium BicarbonateHCID 90281188N-((S)-1-(3-bromo-6-(3-hydroxy-3-methylazetidin-1-yl)pyridin-2-yl)-2-(3,5-difluorophenyl)ethyl)-2-((3bS,4aR)-3-(difluoromethyl)-5,5-difluoro-3b,4,4a,5-tetrahydro-1H-cyclopropa[3,4]cyclopenta[1,2-c]pyrazol-1-yl)acetamideHCID 90281195N-(1-methyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazol-3-yl)methanesulfonamide

生成物 1

HCID 90281416
2-((3bS,4aR)-3-(difluoromethyl)-5,5-difluoro-3b,4,4a,5-tetrahydro-1H-cyclopropa[3,4]cyclopenta[1,2-c]pyrazol-1-yl)-N-((S)-2-(3,5-difluorophenyl)-1-(6-(3-hydroxy-3-methylazetidin-1-yl)-3-(1-methyl-3-(methylsulfonamido)-1H-indazol-7-yl)pyridin-2-yl)ethyl)acetamide

試薬・触媒・溶媒 2

HCID 11050900Dichlorobis(tricyclohexylphosphine)pallium (II)触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
150 °C

実験手順

In a microwave tube were charged with of N—((S)-1-(3-bromo-6-(3-hydroxy-3-methylazetidin-1-yl)pyridin-2-yl)-2-(3,5-difluorophenyl)ethyl)-2-((3bS,4aR)-3-(difluoromethyl)-5,5-difluoro-3b,4,4a,5-tetrahydro-1H-cyclopropa[3,4]cyclopenta[1,2-c]pyrazol-1-yl)acetamide (45 mg, 0.07 mmol), N-(1-methyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazol-3-yl)methanesulfonamide (36 mg, 0.1 mmol) and PdCl2[P(Cy)3]2 (5 mg, 0.007 mmol). To the mixture was added 1.4 mL of 1,4-dioxane and 0.2 mL of sodium bicarbonate aqueous solution (1M). The system was purged with argon and then the microwave tube was sealed and the reaction mixture was heated up in a microwave synthesizer at 150° C. for 20 min. After cooled down to room temperature, it was partitioned between EtOAc and water. The organic layer was separated and washed with brine, then dried over MgSO4, filtered and concentrated. The residue was purified by reverse phase HPLC eluting with acetonitrile and water (with 0.1% TFA) to afford the title product. 1H NMR (400 MHz, methanol-d4) δ 7.79 (dd, 1H), 7.51 (dd, 1H), 7.29-6.45 (m, 5H), 6.48-6.24 (m, 2H), 4.85 (m, 3H), 4.19-3.91 (m, 4H), 3.58-2.75 (m, 8H), 2.49 (m, 2H), 1.61 (d, J=2.2 Hz, 3H), 1.41 (q, J=7.0 Hz, 1H), 1.20-0.83 (m, 1H). MS (m/z) 789.11 [M+H]+.

後処理

  1. customThe system was purged with argon
  2. customthe microwave tube was sealed
  3. temperatureAfter cooled down to room temperature
  4. customit was partitioned between EtOAc and water
  5. customThe organic layer was separated
  6. washwashed with brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by reverse phase HPLC
  11. washeluting with acetonitrile and water (with 0.1% TFA)

出典と根拠

ORDレコード
ord-ef0ba380fa89414ca98c0965fbfd08b0
出典データセット
uspto-grants-2015_06
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09050344B2

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