Trifluoroacetic acid → 2-(3-Fluoro-phenyl)-4-methyl-pyrimidine-5-carboxylic acid 3-(methanesulfonylamino-methyl)-benzylamide

HRID 219662Notes

Reaction equation

HRID 219662 reaction equation
C(OC(=O)[NH:7][CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([CH2:15][NH:16][C:17]([C:19]2[C:20]([CH3:32])=[N:21][C:22]([C:25]3[CH:30]=[CH:29][CH:28]=[C:27]([F:31])[CH:26]=3)=[N:23][CH:24]=2)=[O:18])[CH:10]=1)(C)(C)C.C(O)(C(F)(F)F)=O.CCN(CC)CC.[CH3:48][S:49](Cl)(=[O:51])=[O:50]>C(Cl)Cl.CCOC(C)=O>[CH3:48][S:49]([NH:7][CH2:8][C:9]1[CH:10]=[C:11]([CH:12]=[CH:13][CH:14]=1)[CH2:15][NH:16][C:17]([C:19]1[C:20]([CH3:32])=[N:21][C:22]([C:25]2[CH:30]=[CH:29][CH:28]=[C:27]([F:31])[CH:26]=2)=[N:23][CH:24]=1)=[O:18])(=[O:51])=[O:50]

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 69123142[3-({[2-(3-Fluoro-phenyl)-4-methyl-pyrimidine-5-carbonyl]-amino}-methyl)-benzyl]-carbamic acid tert-butyl ester

Product 1

HCID 166657822-(3-Fluoro-phenyl)-4-methyl-pyrimidine-5-carboxylic acid 3-(methanesulfonylamino-methyl)-benzylamideYield 64%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of [3-({[2-(3-fluoro-phenyl)-4-methyl-pyrimidine-5-carbonyl]-amino}-methyl)-benzyl]-carbamic acid tert-butyl ester (0.05 g, 0.111 mmol) in DCM (2 mL) at 0° C. is added TFA (0.013 mL. 0.111 mmol) and the mixture is stirred for 2.5 hours. The mixture is concentrated in vacuo. The residue is dissolved in THF (2 mL). Et3N (0.05 mL, 0.333 mmol) and methanesulfonyl chloride (0.010 mL, 0.133 mmol) are added and the mixture is stirred for 12 hours. The mixture is diluted with EtOAc (100 mL), washed with saturated aqueous NH4Cl (2×50 mL), dried with Na2SO4, filtered, and concentrated in vacuo. The residue is purified by flash chromatography eluting with 20%-80% EtOAc/heptane to afford 2-(3-fluoro-phenyl)-4-methyl-pyrimidine-5-carboxylic acid 3-(methanesulfonylamino-methyl)-benzylamide (0.03 g, 64%) as a powder. MS: 429 (M+H); 1H NMR (300 MHz, DMSO-d6): δ 2.65 (s, 3H), 2.86 (s, 3H), 4.18 (d, J=6.3 Hz, 2H), 4.50 (d, J=5.9 Hz, 2H), 7.27-7.45 (m, 3H), 7.62 (m, 2H), 8.13 (m, 1H), 8.28 (m, 1H), 8.90 (s, 1H), 9.25 (m, 1H); IC50=48.5 nM.

Workup

  1. concentrationThe mixture is concentrated in vacuo
  2. dissolutionThe residue is dissolved in THF (2 mL)
  3. stirringthe mixture is stirred for 12 hours
  4. washwashed with saturated aqueous NH4Cl (2×50 mL)
  5. dry with materialdried with Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue is purified by flash chromatography
  9. washeluting with 20%-80% EtOAc/heptane

Sources & evidence

ORD record
ord-1319b54d15d34811a7542ddce2bf1084
Source dataset
uspto-grants-2012_06
Patent number
US08202863B2

Reaction notes

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