Thionyl Chloride → 4-(4-chloro-5-trifluoromethyl-pyrimidin-2-ylamino)-3-methoxy-N-(1-methyl-piperidin-4-yl)-benzamide

HRID 1626357Notes

Reaction equation

HRID 1626357 reaction equation
[Cl:1][C:2]1[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][N:5]=[C:4]([NH:12][C:13]2[CH:21]=[CH:20][C:16]([C:17]([OH:19])=O)=[CH:15][C:14]=2[O:22][CH3:23])[N:3]=1.S(Cl)(Cl)=O.[NH2:28][CH:29]1[CH2:34][CH2:33][N:32]([CH3:35])[CH2:31][CH2:30]1.C(N(C(C)C)CC)(C)C>C1(C)C=CC=CC=1.C1COCC1>[Cl:1][C:2]1[C:7]([C:8]([F:10])([F:9])[F:11])=[CH:6][N:5]=[C:4]([NH:12][C:13]2[CH:21]=[CH:20][C:16]([C:17]([NH:28][CH:29]3[CH2:34][CH2:33][N:32]([CH3:35])[CH2:31][CH2:30]3)=[O:19])=[CH:15][C:14]=2[O:22][CH3:23])[N:3]=1

Participants

7

Reactant 4

HCID 24386Thionyl ChlorideHCID 81531DiisopropylethylamineHCID 27375314-Amino-1-methylpiperidineHCID 589063992-(4-Carboxy-2-methoxy-phenylamino)-4-chloro-5-trifluoromethyl-pyrimidine

Product 1

HCID 582009164-(4-chloro-5-trifluoromethyl-pyrimidin-2-ylamino)-3-methoxy-N-(1-methyl-piperidin-4-yl)-benzamide

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
110 °C

Procedure

4-(4-chloro-5-trifluoromethyl-pyrimidin-2-ylamino)-3-methoxy-benzoic acid (5 g) is suspended in toluene (150 mL) and combined with thionyl chloride (1.77 mL), stirred for 2 h at 110° C. and after cooling the solvent is eliminated in vacuo. The residue is taken up in THF (50 mL), cooled to 0° C. and a solution of 4-amino-1-methylpiperidine (1.396 g) and diisopropylethylamine (4.19 mL) is added dropwise thereto. Then the reaction mixture is left to warm up to RT and stirred overnight. After filtering, the residue is dried overnight at 50° C.

Workup

  1. temperatureafter cooling the solvent
  2. temperaturecooled to 0° C.
  3. waitThen the reaction mixture is left
  4. temperatureto warm up to RT
  5. stirringstirred overnight
  6. filtrationAfter filtering
  7. customthe residue is dried overnight at 50° C.

Sources & evidence

ORD record
ord-2225b8238be5420d9a64f2a7dccfb7a4
Source dataset
uspto-grants-2014_07
Patent number
US08785464B2

Reaction notes

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