Dimethylamine → 3-(1,1-Dioxothiomorpholin-4-yl)-3-{3-[3-(2-methoxy-phenyl)-1h-pyrrolo[2,3-b]pyridin-5-yl]-phenyl}-n,n-dimethyl-propionamide

HRID 886564ノート

反応式

HRID 886564 の反応式
[O:1]=[S:2]1(=O)[CH2:7][CH2:6][N:5]([CH:8]([C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([C:19]3[CH:20]=[C:21]4[C:27]([C:28]5[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=5[O:34][CH3:35])=[CH:26][N:25](S(C5C=CC(C)=CC=5)(=O)=O)[C:22]4=[N:23][CH:24]=3)[CH:14]=2)[CH2:9][C:10](O)=[O:11])[CH2:4][CH2:3]1.[CH3:47][NH:48][CH3:49].C(N(C(C)C)CC)(C)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.[OH-:83].[K+]>CN(C=O)C.CO>[O:83]=[S:2]1(=[O:1])[CH2:3][CH2:4][N:5]([CH:8]([C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([C:19]3[CH:20]=[C:21]4[C:27]([C:28]5[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=5[O:34][CH3:35])=[CH:26][NH:25][C:22]4=[N:23][CH:24]=3)[CH:14]=2)[CH2:9][C:10]([N:48]([CH3:49])[CH3:47])=[O:11])[CH2:6][CH2:7]1

参加物

8

反応物 5

HCID 674DimethylamineHCID 14797Potassium HydroxideHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 598250103-(1,1-dioxothiomorpholin-4-yl)-3-{3-[3-(2-methoxy-phenyl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-phenyl}-propionic acid

生成物 1

HCID 251564633-(1,1-Dioxothiomorpholin-4-yl)-3-{3-[3-(2-methoxy-phenyl)-1h-pyrrolo[2,3-b]pyridin-5-yl]-phenyl}-n,n-dimethyl-propionamide収率 39%

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 6228Dimethylformamide溶媒

実験手順

To a solution of 3-(1,1-dioxothiomorpholin-4-yl)-3-{3-[3-(2-methoxy-phenyl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-phenyl}-propionic acid (100 mg, 0.15 mmol), dimethylamine (2 N solution in THF, 0.15 mL, 0.30 mmol), diisopropylethylamine (23 mg, 0.18 mmol) in DMF (1 mL) was added O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (68 mg, 0.18 mmol). The resulting solution was stirred at room temperature for 1 hour. Methanol (1 mL) and potassium hydroxide (50% w/v in water, 0.2 mL) were added and the resulting mixture was stirred for 30 minutes. The mixture was directly purified by mass-triggered reverse-phase HPLC to afford 3-(1,1-dioxothiomorpholin-4-yl)-3-{3-[3-(2-methoxy-phenyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-phenyl}-N,N-dimethyl-propionamide as a white solid (31 mg, 39%). MS: m/z 533 (M+H+). 1H NMR (500 MHz, DMSO-d6) δ 2.75 (s, 3H), 2.82 (br, 2H), 2.88 (dd, 1H), 2.96 (br, 2H), 3.02 (s, 3H), 3.07 (br, 4H), 3.105 (dd, 1H), 3.83 (s, 3H), 4.41 (br, 1H), 7.05 (t, 1H), 7.15 (d, 1H), 7.30 (t, 1H), 7.30 (dt, 1H), 7.31 (d, 1H), 7.44 (t, 1H), 7.61 (d, 1H), 7.65 (s, 1H), 7.74 (d, 1H), 8.18 (d, 1H), 8.57 (d, 1H), 11.93 (s, 1H).

後処理

  1. stirringthe resulting mixture was stirred for 30 minutes
  2. customThe mixture was directly purified by mass-triggered reverse-phase HPLC

出典と根拠

ORDレコード
ord-405b795280934910a62d1645ac992b0b
出典データセット
uspto-grants-2012_08
特許番号
US08242280B2

反応ノート

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