Diisopropylethylamine → 2-(4-Fluorophenyl)-4-methylpyrimidine-5-carboxylic acid 3-methylsulfamoyl-benzylamide

HRID 219657Notes

Reaction equation

HRID 219657 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:13]=[C:12]([CH3:14])[C:11]([C:15]([OH:17])=O)=[CH:10][N:9]=2)=[CH:4][CH:3]=1.C(N(C(C)C)CC)(C)C.[CH3:27][NH:28][S:29]([C:32]1[CH:33]=[C:34]([CH:37]=[CH:38][CH:39]=1)[CH2:35][NH2:36])(=[O:31])=[O:30]>CN(C=O)C>[CH3:27][NH:28][S:29]([C:32]1[CH:33]=[C:34]([CH:37]=[CH:38][CH:39]=1)[CH2:35][NH:36][C:15]([C:11]1[C:12]([CH3:14])=[N:13][C:8]([C:5]2[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=2)=[N:9][CH:10]=1)=[O:17])(=[O:30])=[O:31]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 167855973-(aminomethyl)-N-methylbenzenesulfonamideHCID 300316142-(4-Fluorophenyl)-4-methylpyrimidine-5-carboxylic acid

Product 1

HCID 598058402-(4-Fluorophenyl)-4-methylpyrimidine-5-carboxylic acid 3-methylsulfamoyl-benzylamideYield 52%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A mixture of 2-(4-fluorophenyl)-4-methylpyrimidine-5-carboxylic acid (232 mg, 1 mmol) and O-(7-azabenzotriazol-1-yl)-N,N,N,N-tetramethyluronium hexafluorophosphate (380 mg 1 mmol) in dry DMF (12 mL) is treated with diisopropylethylamine (0.18 mL) and stirred at room temperature for 30 min. A solution of 3-methylsulfamoylbenzylamine (300 mg, 1.5 mmol) in dry DMF (1.5 mL) is added and the mixture is stirred at room temperature for 24 hours. The solvent is removed and the residue is partitioned between EtOAc and water. The organic phase is separated, washed with saturated NaHCO3, water and brine, dried (MgSO4), filtered and concentrated in vacuo. The residue is purified by column chromatography eluting with 60% EtOAc in heptane to afford 2-(4-fluorophenyl)-4-methylpyrimidine-5-carboxylic acid 3-methylsulfamoyl-benzylamide (210 mg, 52%) as a solid. MS: 415 (M+H); 1H NMR (300 MHz, DMSO-d6): δ 2.42 (s, 3H), 2.63 (s, 3H), 4.60 (d, 2H), 7.37-7.40 (t, 2H), 7.50 (s, 1H), 7.60-7.75 (m, 3H), 7.80 (s, 1H), 8.45-8.50 (dd, 2H), 8.88 (s, 1H), 9.30 (t, 1H).

Workup

  1. stirringthe mixture is stirred at room temperature for 24 hours
  2. customThe solvent is removed
  3. customthe residue is partitioned between EtOAc and water
  4. customThe organic phase is separated
  5. washwashed with saturated NaHCO3, water and brine
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue is purified by column chromatography
  10. washeluting with 60% EtOAc in heptane

Sources & evidence

ORD record
ord-98e2d8c078f5496ca0ab502f663975b3
Source dataset
uspto-grants-2012_06
Patent number
US08202863B2

Reaction notes

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