Ammonia → HCID 46917572, compound

HRID 1256463Notes

Reaction equation

HRID 1256463 reaction equation
[F:1][CH:2]([F:44])[C:3]1[N:7]([C:8]2[N:13]=[C:12]([N:14]3[CH2:19][CH2:18][N:17]([S:20]([CH3:23])(=[O:22])=[O:21])[CH2:16][CH2:15]3)[N:11]=[C:10]([N:24]3[CH2:29][CH2:28][O:27][CH2:26][CH2:25]3)[N:9]=2)[C:6]2[CH:30]=[C:31]([NH:36]C(=O)OC(C)(C)C)[CH:32]=[C:33]([O:34][CH3:35])[C:5]=2[N:4]=1.C(O)(C(F)(F)F)=O.N>C(Cl)Cl.O>[F:44][CH:2]([F:1])[C:3]1[N:7]([C:8]2[N:13]=[C:12]([N:14]3[CH2:15][CH2:16][N:17]([S:20]([CH3:23])(=[O:21])=[O:22])[CH2:18][CH2:19]3)[N:11]=[C:10]([N:24]3[CH2:29][CH2:28][O:27][CH2:26][CH2:25]3)[N:9]=2)[C:6]2[CH:30]=[C:31]([NH2:36])[CH:32]=[C:33]([O:34][CH3:35])[C:5]=2[N:4]=1

Participants

6

Reactant 3

HCID 222AmmoniaHCID 6422Trifluoroacetic acidHCID 66698055tert-butyl 2-(difluoromethyl)-4-methoxy-1-[4-[4-(methylsulfonyl)-1-piperazinyl]-6-(4-morpholinyl)-1,3,5-triazin-2-yl]-1H-benzimidazol-6-ylcarbamate

Product 1

HCID 46917572HCID 46917572, compoundYield 86.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

A mixture of tert-butyl 2-(difluoromethyl)-4-methoxy-1-[4-[4-(methylsulfonyl)-1-piperazinyl]-6-(4-morpholinyl)-1,3,5-triazin-2-yl]-1H-benzimidazol-6-ylcarbamate (0.20 g, 0.31 mmol) and TFA (5 mL) in CH2Cl2 (20 mL) was stirred at room temperature for 2 hrs. The mixture was diluted with CH2Cl2 (100 mL) and water (100 mL), and the aqueous layer was made basic with aqueous NH3. The organic layer was dried and concentrated under vacuum. Recrystallization of the residue from CH2Cl2/MeOH gave 0.145 g (86% yield) of 2-(difluoromethyl)-4-methoxy-1-[4-[4-(methylsulfonyl)-1-piperazinyl]-6-(4-morpholinyl)-1,3,5-triazin-2-yl]-1H-benzimidazol-6-ylamine: mp 280-283° C.; 1H NMR (CDCl3) δ 7.59 (t, JHF=53.4 Hz, 1H), 7.05 (d, J=1.7 Hz, 1H), 6.26 (d, J=1.7 Hz, 1H), 5.45 (s, exchangeable with D2O, 2H), 3.93 (m, 4H), 3.87 (s, 3H), 3.80 (m, 4H), 3.69 (m, 4H), 3.24 (m, 4H), 2.91 (s, 3H); Anal. Calcd. for C21H27F2N9O4S: C, 46.75; H, 5.0; N, 23.4. Found: C, 47.0; H, 5.2; N, 23.4%.

Workup

  1. customThe organic layer was dried
  2. concentrationconcentrated under vacuum
  3. customRecrystallization of the residue from CH2Cl2/MeOH

Sources & evidence

ORD record
ord-0dd9c4c83450463f8eaffb304d64c383
Source dataset
uspto-grants-2013_06
Patent number
US08461158B2

Reaction notes

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