Water → 4-[2-[2-(Difluoromethyl)-4-methoxybenzimidazol-1-yl]-9-(1-methylsulfonylpiperidin-4-yl)purin-6-yl]morpholine

HRID 1256576Notes

Reaction equation

HRID 1256576 reaction equation
[CH3:1][S:2](Cl)(=[O:4])=[O:3].[F:6][CH:7]([F:40])[C:8]1[N:12]([C:13]2[N:21]=[C:20]3[C:16]([N:17]=[CH:18][N:19]3[CH:22]3[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]3)=[C:15]([N:28]3[CH2:33][CH2:32][O:31][CH2:30][CH2:29]3)[N:14]=2)[C:11]2[CH:34]=[CH:35][CH:36]=[C:37]([O:38][CH3:39])[C:10]=2[N:9]=1.C([O-])([O-])=O.[K+].[K+].O>C(Cl)Cl>[F:40][CH:7]([F:6])[C:8]1[N:12]([C:13]2[N:21]=[C:20]3[C:16]([N:17]=[CH:18][N:19]3[CH:22]3[CH2:27][CH2:26][N:25]([S:2]([CH3:1])(=[O:4])=[O:3])[CH2:24][CH2:23]3)=[C:15]([N:28]3[CH2:29][CH2:30][O:31][CH2:32][CH2:33]3)[N:14]=2)[C:11]2[CH:34]=[CH:35][CH:36]=[C:37]([O:38][CH3:39])[C:10]=2[N:9]=1

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 31297Methanesulfonyl chlorideHCID 666981762-[2-(Difluoromethyl)-4-methoxy-1h-benzimidazol-1-yl]-6-(4-morpholinyl)-9-(4-piperidinyl)-9h-purine

Product 1

HCID 469176534-[2-[2-(Difluoromethyl)-4-methoxybenzimidazol-1-yl]-9-(1-methylsulfonylpiperidin-4-yl)purin-6-yl]morpholineYield 88.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Methanesulfonyl chloride (0.08 mL, 1.03 mmol) was added dropwise to a mixture of the above amine (102 mg, 0.211 mmol) and powdered K2CO3 (263 mg, 1.90 mmol) in CH2Cl2 (10 mL) at 0° C. The mixture was allowed to warm to room temperature and was stirred for 5 hrs. Water was added, the phases were separated, and the aqueous phase was extracted with CH2Cl2. The combined organic extracts were dried (Na2SO4) and the solvent was removed under vacuum. Recrystallization from CH2Cl2/MeOH gave 2-[2-(difluoromethyl)-4-methoxy-1H-benzimidazol-1-yl]-9-[1-(methylsulfonyl)-4-piperidinyl]-6-(4-morpholinyl)-9H-purine (105 mg, 88%): mp 236-239° C.; 1H NMR (CDCl3) δ 7.84 (s, 1H), 7.76 (dd, J=8.4, 0.5 Hz, 1H), 7.42 (t, THF=53.6 Hz, 1H), 7.36 (t, J=8.2 Hz, 1H), 6.81 (d, J=7.8 Hz, 1H), 4.57 (tt, J=11.7, 4.4 Hz, 1H), 4.38 (br s, 4H), 4.09 (m, 2H), 4.06 (s, 3H), 3.88 (t, J=4.8 Hz, 4H), 2.96 (dt, J=12.5, 2.8 Hz, 2H), 2.88 (s, 3H), 2.35-2.20 (m, 4H); Anal. Calcd. for C24H28F2N8O4S: C, 51.2; H, 5.0; N, 19.9. Found: C, 51.0; H, 4.9; N, 19.7%.

Workup

  1. customthe phases were separated
  2. extractionthe aqueous phase was extracted with CH2Cl2
  3. dry with materialThe combined organic extracts were dried (Na2SO4)
  4. customthe solvent was removed under vacuum
  5. customRecrystallization from CH2Cl2/MeOH

Sources & evidence

ORD record
ord-07d555ac5132465c82ca5b60ff365783
Source dataset
uspto-grants-2013_06
Patent number
US08461158B2

Reaction notes

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