Methanesulfonic Acid → Methanesulfonic Acid

HRID 1427379Notes

Reaction equation

HRID 1427379 reaction equation
Cl[C:2]1[N:7]=[C:6]([O:8][C:9]2[CH:14]=[CH:13][C:12]([N+:15]([O-:17])=[O:16])=[CH:11][CH:10]=2)[C:5]([C:18]([F:21])([F:20])[F:19])=[CH:4][N:3]=1.[NH2:22][C:23]1[CH:39]=[CH:38][C:26]([C:27]([N:29]([CH3:37])[CH:30]2[CH2:35][CH2:34][N:33]([CH3:36])[CH2:32][CH2:31]2)=[O:28])=[CH:25][CH:24]=1.C[Si](Cl)(C)C.[CH3:45][S:46]([OH:49])(=[O:48])=[O:47].[OH-].[Na+]>CN1CCCC1=O.C(Cl)Cl>[CH3:37][N:29]([CH:30]1[CH2:35][CH2:34][N:33]([CH3:36])[CH2:32][CH2:31]1)[C:27](=[O:28])[C:26]1[CH:38]=[CH:39][C:23]([NH:22][C:2]2[N:7]=[C:6]([O:8][C:9]3[CH:14]=[CH:13][C:12]([N+:15]([O-:17])=[O:16])=[CH:11][CH:10]=3)[C:5]([C:18]([F:21])([F:20])[F:19])=[CH:4][N:3]=2)=[CH:24][CH:25]=1.[CH3:45][S:46]([OH:49])(=[O:48])=[O:47]

Participants

9

Reactant 5

HCID 6395Methanesulfonic AcidHCID 6397ChlorotrimethylsilaneHCID 14798Sodium HydroxideHCID 167814824-amino-N-methyl-N-(1-methyl-piperidin-4-yl)-benzamideHCID 509176332-Chloro-4-(4-nitrophenyloxy)-5-trifluoromethylpyrimidine

Product 2

HCID 6395Methanesulfonic AcidHCID 66927225N-methyl-N-(1-methyl-piperidin-4-yl)-4-[4-(4-nitro-phenoxy)-5-trifluoromethyl-pyrimidin-2-ylamino]-benzamide

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
55 °C

Procedure

Alternatively, 1.0 g of 2-chloro-4-(4-nitrophenyloxy)-5-trifluoromethylpyrimidine is dissolved in 5 mL of 1-methyl-2-pyrrolidinone (NMP). 1.44 g of the mono-4-toluenesulfonic acid salt of 4-amino-N-methyl-N-(1-methyl-piperidin-4-yl)-benzamide, 76 μL of trimethylsilylchloride (as water scavenger) and 60 mg methanesulfonic acid are added. The suspension is stirred for 18 hours at 55° C. 15 mL methylenechloride and 10 mL 2N sodium hydroxide solution are added. The organic phase is separated and the solvent is reduced so that 5 g of a concentrated solution remain. To this solution 20 mL 2-propanol and 0.32 g methanesulfonic acid are added. Crystallization occurs. The suspension is filtered, washed and dried to obtain 1.5 g (77% of theory) of product N-methyl-N-(1-methyl-piperidin-4-yl)-4-[4-(4-nitro-phenoxy)-5-trifluoromethyl-pyrimidin-2-ylamino]-benzamide as methanesulfonic acid salt.

Workup

  1. customThe organic phase is separated
  2. additionTo this solution 20 mL 2-propanol and 0.32 g methanesulfonic acid are added
  3. customCrystallization
  4. filtrationThe suspension is filtered
  5. washwashed
  6. customdried

Sources & evidence

ORD record
ord-7721a2bc27214d9e9ecdb9a5a0f3b621
Source dataset
uspto-grants-2015_01
Patent number
US08933227B2

Reaction notes

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