Trifluoroacetic acid → HCID 11627396, compound

HRID 646907Notes

Reaction equation

HRID 646907 reaction equation
[CH3:1][CH:2]1[CH2:7][CH2:6][N:5]([C:8]2[CH:13]=[C:12]([CH:14]3[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]3)[CH:11]=[CH:10][C:9]=2[NH:20][C:21]([C:23]2[NH:24][CH:25]=[C:26]([C:28]#[N:29])[CH:27]=2)=[O:22])[CH2:4][CH2:3]1.FC(F)(F)C(O)=O.[C:37](Cl)(=[O:44])[C:38]1[CH:43]=[CH:42][CH:41]=[N:40][CH:39]=1.C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C.CCOC(C)=O>[CH3:1][CH:2]1[CH2:7][CH2:6][N:5]([C:8]2[CH:13]=[C:12]([CH:14]3[CH2:19][CH2:18][N:17]([C:37]([C:38]4[CH:39]=[N:40][CH:41]=[CH:42][CH:43]=4)=[O:44])[CH2:16][CH2:15]3)[CH:11]=[CH:10][C:9]=2[NH:20][C:21]([C:23]2[NH:24][CH:25]=[C:26]([C:28]#[N:29])[CH:27]=2)=[O:22])[CH2:4][CH2:3]1

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 10340Sodium CarbonateHCID 82604Nicotinoyl chlorideHCID 11671730HCID 11671730, compound

Product 1

HCID 11627396HCID 11627396, compoundYield 98%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 4-cyano-1H-pyrrole-2-carboxylic acid [2-(4-methyl-piperidin-1-yl)-4-piperidin-4-yl-phenyl]-amide bis(trifluoroacetic acid salt) (as prepared in Example 35, 25.0 mg, 0.0400 mmol), nicotinoyl chloride (10.8 mg, 0.0600 mmol) and anh Na2CO3 (21.0 mg, 0.200 mmol) in 1 mL of DMF was stirred at RT for 2 days. Treated with 30 mL of EtOAc, the mixture was washed with H2O (3×10 mL), brine (10 mL) and dried (Na2SO4). Removal of the solvent under reduced pressure followed by flash chromatography of the residue on silica gel (1-3% MeOH/DCM) gave 19.6 mg (98%) of the title compound as a white solid: 1H-NMR (CDCl3; 400 MHz): δ 10.67, (s, 1H), 9.17 (s, 1H), 8.74 (d, 1H, J=1.6 Hz), 8.69 (dd, 1H, J=4.5, 1.6 Hz), 8.32 (d, 1H, J=8.4 Hz), 7.82 (ddd, 1H, J=7.7, 1.9, 1.9 Hz), 7.47 (dd, 1H, J=3.3, 1.2 Hz), 7.40 (dd, 1H, J=8.0, 4.9 Hz), 7.07 (d, 1H, J=1.9 Hz), 7.04 (dd, 1H, J=8.4, 1.9 Hz), 6.87 (s, 1H), 4.90 (s, 1H), 3.87 (s, 1H), 3.22 (s, 1H), 2.69-3.00 (m, 6H), 1.53-2.06 (m, 7H), 1.35-1.46 (m, 2H), 1.00 (d, 3H, J=6.5 Hz). Mass spectrum (ESI, m/z): Calcd. for C29H32N6O2, 497.3 (M+H), found 497.2.

Workup

  1. washthe mixture was washed with H2O (3×10 mL), brine (10 mL)
  2. dry with materialdried (Na2SO4)
  3. customRemoval of the solvent under reduced pressure

Sources & evidence

ORD record
ord-9de40d263ab7462fb1e77593d985dcbd
Source dataset
uspto-grants-2010_04
Patent number
US07705042B2

Reaction notes

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