Ammonia → 5-[2-(Difluoromethyl)-4-methoxy-1h-benzimidazol-1-yl]-7-(4-morpholinyl)-3-(4-piperidinyl)-3h-[1,2,3]triazolo[4,5-d]pyrimidine

HRID 516419Notes

Reaction equation

HRID 516419 reaction equation
[F:1][CH:2]([F:42])[C:3]1[N:7]([C:8]2[N:9]=[C:10]([N:30]3[CH2:35][CH2:34][O:33][CH2:32][CH2:31]3)[C:11]3[N:16]=[N:15][N:14]([CH:17]4[CH2:22][CH2:21][N:20](C(OC(C)(C)C)=O)[CH2:19][CH2:18]4)[C:12]=3[N:13]=2)[C:6]2[CH:36]=[CH:37][CH:38]=[C:39]([O:40][CH3:41])[C:5]=2[N:4]=1.C(O)(C(F)(F)F)=O.N>C(Cl)Cl>[F:42][CH:2]([F:1])[C:3]1[N:7]([C:8]2[N:9]=[C:10]([N:30]3[CH2:31][CH2:32][O:33][CH2:34][CH2:35]3)[C:11]3[N:16]=[N:15][N:14]([CH:17]4[CH2:18][CH2:19][NH:20][CH2:21][CH2:22]4)[C:12]=3[N:13]=2)[C:6]2[CH:36]=[CH:37][CH:38]=[C:39]([O:40][CH3:41])[C:5]=2[N:4]=1

Participants

5

Reactant 3

HCID 222AmmoniaHCID 6422Trifluoroacetic acidHCID 66698113tert-butyl 4-[5-[2-(difluoromethyl)-4-methoxy-1H-benzimidazol-1-yl]-7-(4-morpholinyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl]-1-piperidinecarboxylate

Product 1

HCID 666981775-[2-(Difluoromethyl)-4-methoxy-1h-benzimidazol-1-yl]-7-(4-morpholinyl)-3-(4-piperidinyl)-3h-[1,2,3]triazolo[4,5-d]pyrimidineYield 85.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Reaction of the above carbamate (158 mg, 0.270 mmol) with an excess of TFA (2 mL) in CH2Cl2 (10 mL) at room temperature for 2 hrs, followed by treatment with aq. NH3 gave 5-[2-(difluoromethyl)-4-methoxy-1H-benzimidazol-1-yl]-7-(4-morpholinyl)-3-(4-piperidinyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine (112 mg, 85%), which was used in the next step without further purification: 1H NMR (CDCl3) δ 7.83 (dd, J=8.4, 0.4 Hz, 1H), 7.46 (t, JHF=53.6 Hz, 1H), 7.38 (t, J=8.2 Hz, 1H), 6.83 (d, J=7.9 Hz, 1H), 4.87 (tt, J=11.7, 4.2 Hz, 1H), 4.80 (br s, 2H), 4.15 (br s, 2H), 4.07 (s, 3H), 3.92 (d, J=15.0 Hz, 4H), 3.34 (m, 2H), 2.88 (dt, J=12.7, 2.5 Hz, 2H), 2.38 (dq, J=12.0, 4.2 Hz, 2H), 2.18 (m, 2H).

Sources & evidence

ORD record
ord-4874431b8a0a46a7ae56051cec6680b9
Source dataset
uspto-grants-2015_08
Patent number
US09108980B2

Reaction notes

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