Dimethylformamide → 4-amino-N-(2-(dimethylamino)ethyl)-3-(3-methoxy-4-(1-methyl-1H-indole-2-carboxamido)phenyl)thieno[3,2-c]pyridine-7-carboxamide

HRID 1270906Notes

Reaction equation

HRID 1270906 reaction equation
[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]([OH:34])=O)=[CH:4][N:3]=1.[CH2:35]([N:37]([CH2:40]C)[CH2:38]C)[CH3:36].C[N:43](C)C=O>>[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]([NH:43][CH2:36][CH2:35][N:37]([CH3:40])[CH3:38])=[O:34])=[CH:4][N:3]=1

Participants

4

Reactant 3

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 184508304-amino-3-(3-methoxy-4-(1-methyl-1H-indole-2-carboxamido)phenyl)thieno[3,2-c]pyridine-7-carboxylic acid

Product 1

HCID 184508434-amino-N-(2-(dimethylamino)ethyl)-3-(3-methoxy-4-(1-methyl-1H-indole-2-carboxamido)phenyl)thieno[3,2-c]pyridine-7-carboxamideYield 36%

Conditions

Temperature
90 °C

Procedure

In a 3-necked round bottom flask were combined 4-amino-3-(3-methoxy-4-{[(1-methyl-1H-indol-2-yl)carbonyl]amino}phenyl)thieno[3,2-c]pyridine-7-carboxylic acid (0.100 g, 0.180 mmol) and trans-dichloro[bis(triphenylphosphine)]palladium (II) (0.012 g, 0.018 mmol). The flask was filled and evacuated with nitrogen gas 4 times, followed by the addition of N,N-dimethylformamide (2.5 mL), triethylamine (0.050 mL, 0.361 mmol), and the appropriate amine (0.032 mg, 0.361 mmol). The flask was then filled and evacuated with carbon monoxide gas 3 times and the reaction mixture heated to 90° C. under an atmosphere of carbon monoxide for 4 hours. The reaction was cooled to room temperature, diluted with methylene chloride (50 mL), and washed with water and brine (50 mL each). The organic layer was separated and dried over magnesium sulfate, filtered, and the solvents removed. The crude product was purified by trituration with ethanol to give the title compound (0.034 mg, 36%) as a tan powder. LCMS (Conditions a): Rt 3.00 minutes, 543.3 (MH+); 1H NMR DMSO-d6δ 9.50 (s, 1H), 8.54 (s, 1H), 8.43 (t, J=5.9 Hz, 1H), 8.00 (d, J=8.2 Hz, 1H), 7.70 (d, J=7.8 Hz, 1H), 7.59 (d, J=8.6 Hz, 1H), 7.58 (s, 1H), 7.35 (s, 1H), 7.32 (d, J=8.6 Hz, 1H), 7.19 (s, 1H), 7.15 (t, J=7.0 Hz, 1H), 7.06 (d, J=7.0 Hz, 1H), 4.04 (s, 3H), 3.91 (s, 3H), 3.40 (m, 2H), 2.43 (m, 2H), 2.20 (s, 6H).

Workup

  1. customIn a 3-necked round bottom flask were combined
  2. additionThe flask was filled
  3. customevacuated with nitrogen gas 4 times
  4. additionThe flask was then filled
  5. customevacuated with carbon monoxide gas 3 times
  6. temperatureThe reaction was cooled to room temperature
  7. additiondiluted with methylene chloride (50 mL)
  8. washwashed with water and brine (50 mL each)
  9. customThe organic layer was separated
  10. dry with materialdried over magnesium sulfate
  11. filtrationfiltered
  12. customthe solvents removed
  13. customThe crude product was purified by trituration with ethanol

Sources & evidence

ORD record
ord-5ad4d5325ac74f98b17a1ba6b155c3aa
Source dataset
uspto-grants-2007_04
Patent number
US07202363B2

Reaction notes

Loading…