Triethylamine → (S)-7-(3-(dimethylamino)pyrrolidine-1-carbonyl)-2-(3-fluoro-4-methoxyphenyl)-5H-pyrido[3,2-b]indole-4-carboxamide

HRID 2410744Notes

Reaction equation

HRID 2410744 reaction equation
[C:1]([C:4]1[C:9]2[NH:10][C:11]3[CH:12]=[C:13]([C:17](O)=[O:18])[CH:14]=[CH:15][C:16]=3[C:8]=2[N:7]=[C:6]([C:20]2[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[C:22]([F:28])[CH:21]=2)[CH:5]=1)(=[O:3])[NH2:2].[CH3:29][N:30]([CH3:36])[CH:31]1[CH2:35][CH2:34][NH:33][CH2:32]1.Cl.CN(C)CCCN=C=NCC.O.ON1C2C=CC=CC=2N=N1.C(N(CC)CC)C>CCOC(C)=O.CN(C)C=O>[CH3:29][N:30]([CH3:36])[C@H:31]1[CH2:35][CH2:34][N:33]([C:17]([C:13]2[CH:14]=[CH:15][C:16]3[C:8]4[N:7]=[C:6]([C:20]5[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[C:22]([F:28])[CH:21]=5)[CH:5]=[C:4]([C:1]([NH2:2])=[O:3])[C:9]=4[NH:10][C:11]=3[CH:12]=2)=[O:18])[CH2:32]1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27585193-(Dimethylamino)pyrrolidineHCID 27960291-Hydroxybenzotriazole hydrateHCID 666054684-carbamoyl-2-(3-fluoro-4-methoxyphenyl)-5H-pyrido[3,2-b]indole-7-carboxylic acid

Product 1

HCID 66604280(S)-7-(3-(dimethylamino)pyrrolidine-1-carbonyl)-2-(3-fluoro-4-methoxyphenyl)-5H-pyrido[3,2-b]indole-4-carboxamideYield 44.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Dimethylformamide (5 mL) was added to a mixture of 4-carbamoyl-2-(3-fluoro-4-methoxyphenyl)-5H-pyrido[3,2-b]indole-7-carboxylic acid (70 mg, 0.19 mmol), (3S)-(+3-(dimethylamino)pyrrolidine (0.070 mL, 0.55 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodimide hydrochloride (106 mg, 0.554 mmol), and 1-hydroxybenzotriazole hydrate (75 mg, 0.55 mmol). After stirring for a few minutes, triethylamine (0.077 mL, 0.55 mmol) was added and the reaction was left stirring overnight. It was diluted with EtOAc, washed with water, dried with sodium sulfate and the solvent was removed. The residue was suspended in DCM at 40° C. for 10 min and then filtered to gave (S)-7-(3-(dimethylamino)pyrrolidine-1-carbonyl)-2-(3-fluoro-4-methoxyphenyl)-5H-pyrido[3,2-b]indole-4-carboxamide (40 mg) as a yellow solid. MS (ESI) m/z 476.2 (M+H). 1H NMR (DMSO-d6) δ ppm 11.71 (1H, br. s.), 8.62 (1H, br. s.), 8.47 (1H, s), 8.30 (1H, dd, J=7.48, 4.43 Hz), 8.09-8.21 (2H, m), 7.92 (2H, m), 7.42 (1H, m), 7.36 (1H, m), 3.95 (3H, s), 3.64-3.82 (1H, m), 3.47-3.63 (2H, m), 3.36 (1H, m), 2.61-2.83 (1H, m), 2.22 (3H, s), 2.11 (3H, s), 2.03 (1 H, br. s.), 1.68-1.85 (1H, m).

Workup

  1. waitthe reaction was left
  2. stirringstirring overnight
  3. washwashed with water
  4. dry with materialdried with sodium sulfate
  5. customthe solvent was removed
  6. filtrationfiltered

Sources & evidence

ORD record
ord-7d2e144fff4b4f01904ebfc566f840ef
Source dataset
uspto-grants-2014_08
Patent number
US08815840B2

Reaction notes

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