Sodium Bicarbonate → 4-cyano-N-(4-(4-methylpiperazin-1-yl)-2-(piperidin-1-yl)phenyl)-1H-pyrrole-2-carboxamide

HRID 646915Notes

Reaction equation

HRID 646915 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([C:8]([OH:10])=O)[NH:6][CH:7]=1)#[N:2].Cl.CN(C)CCCN=C=NCC.OC1C2N=NNC=2C=CC=1.[CH3:33][N:34]1[CH2:39][CH2:38][N:37]([C:40]2[CH:45]=[CH:44][C:43]([NH:46]C(C3OC(C#N)=CC=3)=O)=[C:42]([N:56]3[CH2:61][CH2:60][CH2:59][CH2:58][CH2:57]3)[CH:41]=2)[CH2:36][CH2:35]1.C(=O)(O)[O-].[Na+]>ClCCl>[CH3:33][N:34]1[CH2:35][CH2:36][N:37]([C:40]2[CH:45]=[CH:44][C:43]([NH:46][C:8]([C:5]3[NH:6][CH:7]=[C:3]([C:1]#[N:2])[CH:4]=3)=[O:10])=[C:42]([N:56]3[CH2:61][CH2:60][CH2:59][CH2:58][CH2:57]3)[CH:41]=2)[CH2:38][CH2:39]1

Participants

7

Reactant 5

HCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 115028715-Cyano-N-[4-(4-Methylpiperazin-1-Yl)-2-Piperidin-1-Ylphenyl]furan-2-CarboxamideHCID 118048114-cyano-1H-pyrrole-2-carboxylic acidHCID 178418300HCID 178418300, compound

Product 1

HCID 116897124-cyano-N-(4-(4-methylpiperazin-1-yl)-2-(piperidin-1-yl)phenyl)-1H-pyrrole-2-carboxamideYield 44%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To 62 mg (0.44 mmol) of 4-cyano-1H-pyrrole-2-carboxylic acid (as prepared in Example 2) in dichloromethane (20 mL) was added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI) (107 mg, 0.560 mmol), hydroxybenzotriazole (HOBt) (65 mg, 0.48 mmol), and 4-(4-methyl-piperazin-1-yl)-2-piperidin-1-yl-phenylamine (as prepared in Example 5, step (b), 100 mg, 0.370 mmol) and the mixture stirred for 24 h at RT. The mixture was poured into satd aq sodium bicarbonate (50 mL) and extracted with dichloromethane (2×20 mL). The organic layers were washed with brine (20 mL), dried over Na2SO4 and the solvent was removed in vacuo. Purification of the resulting residue by silica gel preparative TLC eluting with 10% methanol in dichloromethane yielded 63 mg (44%) of the title compound as a tan solid. 1H-NMR (400 MHz, CDCl3): δ 11.09 (br s, 1H), 9.11 (s, 1H), 8.25 (d, 1H, J=8.9 Hz), 7.45 (d, 1H, J=1.3 Hz), 6.88 (d, 1H, J=1.1 Hz), 6.81 (d, 1H, J=2.6 Hz), 6.75 (dd, 1H, J=8.9, 2.6), 3.21 (m, 4H), 2.84 (m, 4H), 2.62 (m, 4H), 2.38 (s, 3H), 1.78 (m, 5H). LC-MS (ESI, m/z): Calcd. for C22H29N6O, 393.2 (M+H); found: 393.2.

Workup

  1. extractionextracted with dichloromethane (2×20 mL)
  2. washThe organic layers were washed with brine (20 mL)
  3. dry with materialdried over Na2SO4
  4. customthe solvent was removed in vacuo
  5. customPurification of the resulting residue by silica gel preparative TLC
  6. washeluting with 10% methanol in dichloromethane

Sources & evidence

ORD record
ord-919e29eaeb484f9ba4f8c9096c1136f5
Source dataset
uspto-grants-2010_04
Patent number
US07705042B2

Reaction notes

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