O-Toluidine → 6-chloro-N-(2-methylphenyl)pyrimidine-4-carboxamide

HRID 1746656

Reaction equation

HRID 1746656 reaction equation
[Cl:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]([C:8](Cl)=[O:9])[CH:3]=1.[NH2:11][C:12]1[C:13]([CH3:18])=[CH:14][CH:15]=[CH:16][CH:17]=1.CCN(C(C)C)C(C)C>C(Cl)Cl>[Cl:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]([C:8]([NH:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[CH3:18])=[O:9])[CH:3]=1

Participants

5

Reactant 3

HCID 7242O-ToluidineHCID 81531DiisopropylethylamineHCID 184220986-Chloropyrimidine-4-carbonyl chloride

Product 1

HCID 594470936-chloro-N-(2-methylphenyl)pyrimidine-4-carboxamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A cooled (0° C.) solution of 6-chloropyrimidine-4-carbonyl chloride (26.76 g; 151 mmol), obtained as described above for Intermediate 7 step 1, in anhydrous DCM (270 ml) was treated dropwise over 25 minutes with a solution of o-toluidine (13.6 ml; 126.0 mmol) and DIEA (43.4 ml; 252 mmol) in anhydrous DCM (100 mL). At the end of addition, the reaction mixture was washed with water then brine, dried over MgSO4, filtered and dried under vacuum to afford the title compound used without further purification as a brown solid. 1H NMR (300 MHz, DMSO-d6) δ 10.47 (1H, br s), 9.32 (1H, d, J=1.0 Hz), 8.25 (1H, d, J=1.0 Hz), 7.65-7.63 (1H, m), 7.34-7.19 (3H, m), 2.31 (3H, s). MS (ESI+): 248.0; MS (ESI−): 246.1. HPLC (Condition A): Rt 4.19 min (HPLC purity 96.0%).

Workup

  1. customobtained
  2. additionAt the end of addition
  3. washthe reaction mixture was washed with water
  4. dry with materialbrine, dried over MgSO4
  5. filtrationfiltered
  6. customdried under vacuum

Sources & evidence

ORD record
ord-6481917ed77b4859acfe52412bb441c8
Source dataset
uspto-grants-2015_10
Patent number
US09150519B2

Linked notes

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