Triethylamine → (S)-4-chloro-7-(2-oxo-2-(2'-oxo-2',3'-dihydro-1'H-spiro[piperidine-4,4'-quinazoline]-1-yl)ethyl)-9-(2,2,2-trifluoroethyl)-6,7,9,10-tetrahydroazepino[3,4-e]indazol-8(3H)-one

HRID 132505ノート

反応式

HRID 132505 の反応式
[Cl:1][C:2]1[C:10]2[NH:9][N:8]=[CH:7][C:6]=2[C:5]2[CH2:11][N:12]([CH2:21][C:22]([F:25])([F:24])[F:23])[C:13](=[O:20])[C@H:14]([CH2:16][C:17](O)=[O:18])[CH2:15][C:4]=2[CH:3]=1.[NH:26]1[C:35]2[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=2)[C:29]2([CH2:40][CH2:39][NH:38][CH2:37][CH2:36]2)[NH:28][C:27]1=[O:41].F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.C(N(CC)CC)C>ClCCl>[Cl:1][C:2]1[C:10]2[NH:9][N:8]=[CH:7][C:6]=2[C:5]2[CH2:11][N:12]([CH2:21][C:22]([F:24])([F:23])[F:25])[C:13](=[O:20])[C@H:14]([CH2:16][C:17](=[O:18])[N:38]3[CH2:37][CH2:36][C:29]4([C:30]5[C:35](=[CH:34][CH:33]=[CH:32][CH:31]=5)[NH:26][C:27](=[O:41])[NH:28]4)[CH2:40][CH2:39]3)[CH2:15][C:4]=2[CH:3]=1

参加物

6

反応物 4

HCID 8471TriethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 497603501'H-Spiro[piperidine-4,4'-quinazolin]-2'(3'H)-oneHCID 59732027(S)-2-(4-chloro-8-oxo-9-(2,2,2-trifluoroethyl)-3,6,7,8,9,10-hexahydroazepino[3,4-e]indazol-7-yl)acetic acid

生成物 1

HCID 11978423(S)-4-chloro-7-(2-oxo-2-(2'-oxo-2',3'-dihydro-1'H-spiro[piperidine-4,4'-quinazoline]-1-yl)ethyl)-9-(2,2,2-trifluoroethyl)-6,7,9,10-tetrahydroazepino[3,4-e]indazol-8(3H)-one収率 79.8%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

To a solution of (S)-2-(4-chloro-8-oxo-9-(2,2,2-trifluoroethyl)-3,6,7,8,9,10-hexahydroazepino[3,4-e]indazol-7-yl)acetic acid (50 mg, 0.133 mmol) in dichloromethane (25 mL) was added 1′H-spiro[piperidine-4,4′-quinazolin]-2′(3′H)-one (31 mg, 0.14 mmol) followed by 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (47 mg, 0.15 mmol) and triethylamine (1.0 mL). After 12 h, the reaction mixture was washed with aqueous NaHCO3 followed by 1.0 M HCl and dried (Na2SO4). The solvent was removed and the crude product was purified by flash chromatography using 7% MeOH in dichloromethane to give (S)-4-chloro-7-(2-oxo-2-(2′-oxo-2′,3′-dihydro-1′H-spiro[piperidine-4,4′-quinazoline]-1-yl)ethyl)-9-(2,2,2-trifluoroethyl)-6,7,9,10-tetrahydroazepino[3,4-e]indazol-8(3H)-one (61 mg, 79%) as awhite powder. MS (ESI) 575 (M+H); Rf=2.133.

後処理

  1. washthe reaction mixture was washed with aqueous NaHCO3
  2. dry with materialdried (Na2SO4)
  3. customThe solvent was removed
  4. customthe crude product was purified by flash chromatography

出典と根拠

ORDレコード
ord-69458b9150c34983897d5516e2277aa9
出典データセット
uspto-grants-2008_06
特許番号
US07384931B2

反応ノート

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