Water → HCID 59506108, compound

HRID 1256559Notes

Reaction equation

HRID 1256559 reaction equation
[CH3:1][S:2](Cl)(=[O:4])=[O:3].[F:6][CH:7]([F:37])[C:8]1[N:12]([C:13]2[N:18]=[C:17]([N:19]3[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]3)[N:16]=[C:15]([CH:25]3[CH2:30][CH2:29][O:28][CH2:27][CH2:26]3)[N:14]=2)[C:11]2[CH:31]=[CH:32][CH:33]=[C:34]([O:35][CH3:36])[C:10]=2[N:9]=1.C([O-])([O-])=O.[K+].[K+].O>C(Cl)Cl>[F:37][CH:7]([F:6])[C:8]1[N:12]([C:13]2[N:18]=[C:17]([N:19]3[CH2:20][CH2:21][N:22]([S:2]([CH3:1])(=[O:4])=[O:3])[CH2:23][CH2:24]3)[N:16]=[C:15]([CH:25]3[CH2:26][CH2:27][O:28][CH2:29][CH2:30]3)[N:14]=2)[C:11]2[CH:31]=[CH:32][CH:33]=[C:34]([O:35][CH3:36])[C:10]=2[N:9]=1

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium Carbonate2×HCID 31297Methanesulfonyl chloride2×HCID 67544630HCID 67544630, compound

Product 1

HCID 59506108HCID 59506108, compoundYield 61%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Methanesulfonyl chloride (0.07 mL, 0.904 mmol) was added drop-wise to a mixture of the above amine (102 mg, 0.229 mmol) and powdered K2CO3 (253 mg, 1.83 mmol) in CH2Cl2 (5 mL) at 0° C. The reaction mixture was stirred at 0° C. for 5 min and allowed to warm to room temperature. After 5 hrs, additional K2CO3 (127 mg, 0.919 mmol) and methanesulfonyl chloride (0.04 mL, 0.517 mmol) were added and the mixture stirred at room temperature for another 16 hrs. Water was added and the layers were separated. The organic layer was dried (Na2SO4) and the solvent was removed under vacuum. Recrystallization from CH2Cl2/MeOH gave 2-(difluoromethyl)-4-methoxy-1-{4-[4-(methylsulfonyl)-1-piperazinyl]-6-tetrahydro-2H-pyran-4-yl-1,3,5-triazin-2-yl}-1H-benzimidazole (73 mg, 61%): mp (CH2Cl2/MeOH) 242-244° C.; 1H NMR (CDCl3) δ 8.00 (dd, J=8.4, 0.6 Hz, 1H), 7.55 (t, JHF=53.5, 1H), 7.40 (t, J=7.9 Hz, 1H), 6.86 (d, J=7.7 Hz, 1H), 4.14-4.09 (m, 6H), 4.06 (s, 3H), 3.56 (m, 2H), 3.37 (br s, 4H), 2.96 (m, 1H), 2.83 (s, 3H), 1.99 (ddd, J=12.1, 7.9, 4.0, 4H); Anal. Calcd. for C22H27F2N7O4S: C, 50.5; H, 5.2; N, 18.7. Found: C, 50.6; H, 5.4; N, 18.6%.

Workup

  1. temperatureto warm to room temperature
  2. waitAfter 5 hrs
  3. stirringthe mixture stirred at room temperature for another 16 hrs
  4. customthe layers were separated
  5. dry with materialThe organic layer was dried (Na2SO4)
  6. customthe solvent was removed under vacuum
  7. customRecrystallization from CH2Cl2/MeOH

Sources & evidence

ORD record
ord-3ed54c6f3fd7447595797f8d85fac011
Source dataset
uspto-grants-2013_06
Patent number
US08461158B2

Reaction notes

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