Diisopropylethylamine → N7-2-[di(2-hydroxyethyl)amino]ethyl-4-amino-3-(3-methoxy-4-[(1-methyl-1H-2-indolyl)carbonyl]aminophenyl)thieno[3,2-c]pyridine-7-carboxamide

HRID 17178

反応式

HRID 17178 の反応式
[NH2:1][C:2]1[C:7]2[C:8]([C:11]3[CH:16]=[CH:15][C:14]([NH:17][C:18]([C:20]4[N:21]([CH3:29])[C:22]5[C:27]([CH:28]=4)=[CH:26][CH:25]=[CH:24][CH:23]=5)=[O:19])=[C:13]([O:30][CH3:31])[CH:12]=3)=[CH:9][S:10][C:6]=2[C:5]([C:32](O)=[O:33])=[CH:4][N:3]=1.CN(C(ON1N=NC2C1=CC=CC=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.O.ON1C2C=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C.[NH2:79][CH2:80][CH2:81][N:82]([CH2:86][CH2:87][OH:88])[CH2:83][CH2:84][OH:85]>CN(C)C=O>[OH:85][CH2:84][CH2:83][N:82]([CH2:86][CH2:87][OH:88])[CH2:81][CH2:80][NH:79][C:32]([C:5]1[C:6]2[S:10][CH:9]=[C:8]([C:11]3[CH:16]=[CH:15][C:14]([NH:17][C:18]([C:20]4[N:21]([CH3:29])[C:22]5[C:27]([CH:28]=4)=[CH:26][CH:25]=[CH:24][CH:23]=5)=[O:19])=[C:13]([O:30][CH3:31])[CH:12]=3)[C:7]=2[C:2]([NH2:1])=[N:3][CH:4]=1)=[O:33]

参加物

7

反応物 5

HCID 81531DiisopropylethylamineHCID 98535N,N-Bis(2-hydroxyethyl)ethylenediamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 27960291-Hydroxybenzotriazole hydrateHCID 184508304-amino-3-(3-methoxy-4-(1-methyl-1H-indole-2-carboxamido)phenyl)thieno[3,2-c]pyridine-7-carboxylic acid

生成物 1

HCID 18450842N7-2-[di(2-hydroxyethyl)amino]ethyl-4-amino-3-(3-methoxy-4-[(1-methyl-1H-2-indolyl)carbonyl]aminophenyl)thieno[3,2-c]pyridine-7-carboxamide

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

A 20 mL scintillation vial was charged with 4-amino-3-(3-methoxy-4-{[(1-methyl-1H-indol-2-yl)carbonyl]amino}phenyl)thieno[3,2-c]pyridine-7-carboxylic acid (0.070 g, 0.148 mmol), 0-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium hexafluorophosphate (0.067 g, 0.177 mmol), 1-hydroxybenzotriazole hydrate (0.024 g, 0.177 mmol) and N,N-dimethylformamide (1.5 mL). To the suspension was added diisopropylethylamine (0.100 mL, 0.592 mmol) and 2-[(2-aminoethyl)(2-hydroxyethyl)amino]ethanol (0.024 mg, 0. 162 mmol). The vial was flushed with nitrogen gas prior to capping, and the reaction mixture was shaken at room temperature for 12 hours. Upon completion of the reaction, methylene chloride (2 mL) and saturated sodium bicarbonate solution (2 mL) were added. The solution was filtered through an Empore™ cartridge, and the solvents removed under reduced pressure. The residues were taken up in a minimal amount of methanol and eluted (gravity) through a Si-carbonate™ cartridge (2 gram, 6 mL). The organic solution obtained was concentrated and the resulting residue triturated with water to give N7-2-[di(2-hydroxyethyl)amino]ethyl-4-amino-3-(3-methoxy-4-[(1-methyl-1H-2-indolyl)carbonyl]aminophenyl)thieno[3,2-c]pyridine-7-carboxamide as a precipitate. The title compound was collected and dried by vacuum filtration (15 mg, 14%). LCMS (Conditions a) Rt 2.62 min., 603.4 (MH+); 1H NMR (400 MHz, DMSO-d6) δ 9.51 (s, 1 H), 8.51 (s, 1 H), 8.39 (t, J=5.5 Hz, 1 H), 7.99 (dd, J=7.8 Hz, 8.2 Hz, 1 H), 7.70 (d, J=8.2 Hz, 1 H), 7.59 (d, J=7.2 Hz, 1 H), 7.58 (s, 1 H), 7.35 (s, 1 H), 7.32 (d, J=8.2 Hz, 1 H), 7.20 (d, J=1.6 Hz, 1 H), 7.15 (dd, J=7.8 Hz, 7.2 Hz, 1 H), 7.07 (dd, J=8.2 Hz, 1.6 Hz, 1 H), 4.41 (t, J=5.8 Hz, 1 H), 4.04 (s, 3 H), 3.91 (s, 3 H), 3.44 (q, J=5.8 Hz, 4 H), 3.34 (m, 2 H), 2.68 (t, J=7.2 Hz, 2 H), 2.61 (t, J=5.8 Hz, 4 H).

後処理

  1. customThe vial was flushed with nitrogen gas
  2. customUpon completion of the reaction, methylene chloride (2 mL) and saturated sodium bicarbonate solution (2 mL)
  3. additionwere added
  4. filtrationThe solution was filtered through an Empore™ cartridge
  5. customthe solvents removed under reduced pressure
  6. washeluted (gravity) through a Si-carbonate™ cartridge (2 gram, 6 mL)
  7. customThe organic solution obtained
  8. concentrationwas concentrated
  9. customthe resulting residue triturated with water

出典と根拠

ORDレコード
ord-83764a514d194aa3920b541556ccdebe
出典データセット
uspto-grants-2010_06
特許番号
US07737160B2

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