Isobutyryl chloride → N-{3-(4-Piperidin-1-ylmethyl-phenyl)-9H-dipyrido[2,3-b;4',3'-d]pyrrol-6-yl}-isobutyramide

HRID 1888575Notes

Reaction equation

HRID 1888575 reaction equation
[N:1]1([CH2:7][C:8]2[CH:13]=[CH:12][C:11]([C:14]3[CH:27]=[N:26][C:17]4[NH:18][C:19]5[CH:24]=[N:23][C:22]([NH2:25])=[CH:21][C:20]=5[C:16]=4[CH:15]=3)=[CH:10][CH:9]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[C:28](Cl)(=[O:32])[CH:29]([CH3:31])[CH3:30].CCN(C(C)C)C(C)C.C(=O)(O)[O-].[Na+]>C(Cl)Cl.CO.O>[N:1]1([CH2:7][C:8]2[CH:13]=[CH:12][C:11]([C:14]3[CH:27]=[N:26][C:17]4[NH:18][C:19]5[CH:24]=[N:23][C:22]([NH:25][C:28](=[O:32])[CH:29]([CH3:31])[CH3:30])=[CH:21][C:20]=5[C:16]=4[CH:15]=3)=[CH:10][CH:9]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

8

Reactant 4

HCID 62325Isobutyryl chlorideHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 58266504HCID 58266504, compound

Product 1

HCID 67203131N-{3-(4-Piperidin-1-ylmethyl-phenyl)-9H-dipyrido[2,3-b;4',3'-d]pyrrol-6-yl}-isobutyramideYield 12.4%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

A suspension of 3-(4-piperidin-1-ylmethyl-phenyl)-9H-dipyrido[2,3-b;4′,3′-d]pyrrol-6-amine (80.9 mg, 0.226 mmol) in DCM (1.8 mL) was treated with isobutyryl chloride (26.3 μL, 0.249 mmol) and DIPEA (118 μL, 0.679 mmol). The reaction mixture was treated with saturated sodium bicarbonate and diluted with 20% MeOH in DCM and water. The layers were separated, the aqueous phase extracted into 20% MeOH in DCM, and the combined organic phase was dried over sodium sulfate and concentrated in vacuo. The resultant residue was dissolved in DCM/methanol, absorbed onto celite, and purified by preparative HPLC (0-30% MeCN/water modified with 0.1% formic acid) to afford an off-white solid (12 mg, 12%). 1H NMR (DMSO-D6, 400 MHz): 12.03 (s, 1H), 10.32 (s, 1H), 8.95 (d, J=2.2 Hz, 1H), 8.90-8.85 (m, 2H), 8.62 (s, 1H), 7.79 (d, J=8.1 Hz, 2H), 7.42 (d, J=8.1 Hz, 2H), 3.48 (s, 2H), 2.79 (dt, J=6.7, 13.5 Hz, 1H), 2.36 (m, 4H), 1.58-1.46 (m, 4H), 1.41 (m, 2H), 1.14 (d, J=6.8 Hz, 6H). LCMS (Method D): RT=7.73 min, M+H+=428.

Workup

  1. customThe layers were separated
  2. extractionthe aqueous phase extracted into 20% MeOH in DCM
  3. dry with materialthe combined organic phase was dried over sodium sulfate
  4. concentrationconcentrated in vacuo
  5. dissolutionThe resultant residue was dissolved in DCM/methanol
  6. customabsorbed onto celite
  7. custompurified by preparative HPLC (0-30% MeCN/water modified with 0.1% formic acid)

Sources & evidence

ORD record
ord-0fa2e5f291cc4a53b408ed18300d9144
Source dataset
uspto-grants-2013_08
Patent number
US08501765B2

Reaction notes

Loading…