Triethylamine → N-((S)-1-(6-chloro-3-(4-chloro-1-methyl-3-(methylsulfonamido)-1H-indazol-7-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

HRID 2170403ノート

反応式

HRID 2170403 の反応式
[NH2:1][C@H:2]([C:12]1[C:17]([C:18]2[CH:19]=[CH:20][C:21]([Cl:33])=[C:22]3[C:26]=2[N:25]([CH3:27])[N:24]=[C:23]3[NH:28][S:29]([CH3:32])(=[O:31])=[O:30])=[CH:16][CH:15]=[C:14]([Cl:34])[N:13]=1)[CH2:3][C:4]1[CH:9]=[C:8]([F:10])[CH:7]=[C:6]([F:11])[CH:5]=1.C(N(CC)CC)C.[F:42][C:43]1([F:60])[C:47]2[N:48]([CH2:55][C:56](O)=[O:57])[N:49]=[C:50]([C:51](F)([F:53])[F:52])[C:46]=2[C@H:45]2[CH2:59][C@@H:44]12.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CC(N(C)C)=O>[Cl:34][C:14]1[N:13]=[C:12]([C@@H:2]([NH:1][C:56](=[O:57])[CH2:55][N:48]2[C:47]3[C:43]([F:42])([F:60])[C@@H:44]4[CH2:59][C@@H:45]4[C:46]=3[C:50]([CH:51]([F:53])[F:52])=[N:49]2)[CH2:3][C:4]2[CH:9]=[C:8]([F:10])[CH:7]=[C:6]([F:11])[CH:5]=2)[C:17]([C:18]2[CH:19]=[CH:20][C:21]([Cl:33])=[C:22]3[C:26]=2[N:25]([CH3:27])[N:24]=[C:23]3[NH:28][S:29]([CH3:32])(=[O:30])=[O:31])=[CH:16][CH:15]=1

参加物

6

反応物 4

HCID 8471TriethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)2 回HCID 90281213(S)-N-(7-(2-(1-amino-2-(3,5-difluorophenyl)ethyl)-6-chloropyridin-3-yl)-4-chloro-1-methyl-1H-indazol-3-yl)methanesulfonamideHCID 90281286(3bS,4aR)-5,5-Difluoro-3b,4,4a,5-tetrahydro-3-(trifluoromethyl)-1H-cyclopropa(3,4)cyclopenta(1,2-c)pyrazole-1-acetic acid

生成物 1

HCID 90281321N-((S)-1-(6-chloro-3-(4-chloro-1-methyl-3-(methylsulfonamido)-1H-indazol-7-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

試薬・触媒・溶媒 1

HCID 31374Dimethylacetamide溶媒

実験手順

To a solution of crude (S)—N-(7-(2-(1-amino-2-(3,5-difluorophenyl)ethyl)-6-chloropyridin-3-yl)-4-chloro-1-methyl-1H-indazol-3-yl)methanesulfonamide (60A, 400 mg, 0.76 mmol) in DMA (6 mL) was added triethylamine (0.32 mL, 2.28 mmol), 2-((3bS,4aR)-5,5-difluoro-3-(trifluoromethyl)-3b,4,4a,5-tetrahydro-1H-cyclopropa[3,4]cyclopenta[1,2-c]pyrazol-1-yl)acetic acid (30J, 0.61 mmol), then HATU (173.4 mg, 0.46 mmol). The reaction mixture was stirred at room temperature for 15 minutes, then additional HATU (86.7 mg, 0.23 mmol) was added. The reaction mixture was stirred at room temperature for an additional 15 minutes. Upon completion, the reaction mixture was concentrated in vacuo and purified by silica gel column chromatography, eluting with 0-100% EtOAc in hexanes to give the title compound (60B). MS (m/z) 790.05 [M+H]+.

後処理

  1. stirringThe reaction mixture was stirred at room temperature for an additional 15 minutes
  2. concentrationUpon completion, the reaction mixture was concentrated in vacuo
  3. custompurified by silica gel column chromatography
  4. washeluting with 0-100% EtOAc in hexanes

出典と根拠

ORDレコード
ord-ae0fb14d069c40ddbadf8a07b9b8abce
出典データセット
uspto-grants-2015_06
特許番号
US09050344B2

反応ノート

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