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Diisopropylethylamine → N-((R)-1-(1H-indazol-5-yl)ethyl)-2-(1,1,1-trifluoro-2-methylpropan-2-yl)-5,6,7,8-tetrahydroquinoline-6-carboxamide

HRID 1697470
ノート
印刷プレビュー

反応式

HRID 1697470 の反応式
Cl.Cl.[NH:3]1[C:11]2[C:6](=[CH:7][C:8]([C@H:12]([NH2:14])[CH3:13])=[CH:9][CH:10]=2)[CH:5]=[N:4]1.[F:15][C:16]([F:34])([F:33])[C:17]([C:20]1[CH:29]=[CH:28][C:27]2[CH2:26][C@@H:25]([C:30](O)=[O:31])[CH2:24][CH2:23][C:22]=2[N:21]=1)([CH3:19])[CH3:18].C(N(CC)C(C)C)(C)C.F[P-](F)(F)(F)(F)F.C[N+](C)=C(N(C)C)ON1C2N=CC=CC=2N=N1>CN1C(=O)CCC1>[NH:3]1[C:11]2[C:6](=[CH:7][C:8]([C@H:12]([NH:14][C:30]([CH:25]3[CH2:24][CH2:23][C:22]4[N:21]=[C:20]([C:17]([CH3:19])([CH3:18])[C:16]([F:34])([F:33])[F:15])[CH:29]=[CH:28][C:27]=4[CH2:26]3)=[O:31])[CH3:13])=[CH:9][CH:10]=2)[CH:5]=[N:4]1
参加物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 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 58118635(S)-2-(1,1,1-trifluoro-2-methylpropan-2-yl)-5,6,7,8-tetrahydroquinoline-6-carboxylic acidHCID 66944333(R)-1-(1H-indazol-5-yl)ethanamine dihydrochloride

生成物 1

HCID 67276550
N-((R)-1-(1H-indazol-5-yl)ethyl)-2-(1,1,1-trifluoro-2-methylpropan-2-yl)-5,6,7,8-tetrahydroquinoline-6-carboxamide
収率 73.3%

試薬・触媒・溶媒 1

HCID 13387N-methyl-2-pyrrolidone溶媒3 回

実験手順

A 2 mL vial was charged sequentially with a solution of (R)-1-(1H-indazol-5-yl)ethanamine dihydrochloride (34 mg, 0.15 mmol) in NMP (0.2 mL), a solution of (S)-2-(1,1,1-trifluoro-2-methylpropan-2-yl)-5,6,7,8-tetrahydroquinoline-6-carboxylic acid (38 mg, 0.13 mmol) and N,N-diisopropylethylamine (93 μL, 0.53 mmol) in NMP (0.1 mL). A solution of N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (61 mg, 0.16 mmol) in NMP (0.3 mL) was added to the resulting mixture and the solution stirred at room temperature. After 30 min the mixture was filtered and purified by reverse-phase HPLC (20-75% MeCN in 10 mM Et2NH/H2O) to afford the amide as a solid (41 mg, 71%). 1H NMR (400 MHz, DMSO-d6) δ 12.99 (br s, 1H), 8.42 (d, J=8.0 Hz, 1H), 8.04 (s, 1H), 7.66 (s, 1H), 7.54 (d, J=8.1 Hz, 1H), 7.50 (d, J=8.6 Hz, 1H), 7.38-7.32 (m, 2H), 5.05 (app pentet, J=7.0 Hz, 1H), 2.96-2.78 (m, 4H), 2.68-2.60 (m, 1H), 2.05-1.97 (m, 1H), 1.82-1.69 (m, 1H), 1.53 (s, 6H), 1.42 (d, J=7.0 Hz, 3H); m/z=431.2 (M+1)+.

後処理

  1. filtrationAfter 30 min the mixture was filtered
  2. custompurified by reverse-phase HPLC (20-75% MeCN in 10 mM Et2NH/H2O)

出典と根拠

ORDレコード
ord-b775e79f801a45e39565322adec365ed
出典データセット
uspto-grants-2012_04
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08163901B2

反応ノート

読み込み中…

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