tert-butyl 4-{[2-[2-(difluoromethyl)-4-methoxy-1H-benzimidazol-1-yl]-6-(4-morpholinyl)-5-nitro-4-pyrimidinyl]amino}-1-piperidinecarboxylate → tert-butyl 4-{[5-amino-2-[2-(difluoromethyl)-4-methoxy-1H-benzimidazol-1-yl]-6-(4-morpholinyl)-4-pyrimidinyl]amino}-1-piperidinecarboxylate

HRID 516414Notes

Reaction equation

HRID 516414 reaction equation
[F:1][CH:2]([F:43])[C:3]1[N:7]([C:8]2[N:13]=[C:12]([NH:14][CH:15]3[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][CH2:16]3)[C:11]([N+:28]([O-])=O)=[C:10]([N:31]3[CH2:36][CH2:35][O:34][CH2:33][CH2:32]3)[N:9]=2)[C:6]2[CH:37]=[CH:38][CH:39]=[C:40]([O:41][CH3:42])[C:5]=2[N:4]=1>CO.C1COCC1.[Pd]>[NH2:28][C:11]1[C:12]([NH:14][CH:15]2[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][CH2:16]2)=[N:13][C:8]([N:7]2[C:6]3[CH:37]=[CH:38][CH:39]=[C:40]([O:41][CH3:42])[C:5]=3[N:4]=[C:3]2[CH:2]([F:1])[F:43])=[N:9][C:10]=1[N:31]1[CH2:32][CH2:33][O:34][CH2:35][CH2:36]1

Participants

4

Reactant 1

HCID 66698145tert-butyl 4-{[2-[2-(difluoromethyl)-4-methoxy-1H-benzimidazol-1-yl]-6-(4-morpholinyl)-5-nitro-4-pyrimidinyl]amino}-1-piperidinecarboxylate

Product 1

HCID 66698143tert-butyl 4-{[5-amino-2-[2-(difluoromethyl)-4-methoxy-1H-benzimidazol-1-yl]-6-(4-morpholinyl)-4-pyrimidinyl]amino}-1-piperidinecarboxylateYield 94%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 21899815MeOH tetrahydrofuranSolvent

Procedure

A mixture of the above nitro compound (700 mg, 1.16 mmol) and 10% Pd on carbon in MeOH/THF (70 mL: 15 mL) was hydrogenated for 5 hrs. The reaction mixture was filtered through celite, the celite pad was washed with MeOH and CH2Cl2, and the solvents were removed under vacuum. Recrystallization from CH2Cl2/MeOH gave tert-butyl 4-{[5-amino-2-[2-(difluoromethyl)-4-methoxy-1H-benzimidazol-1-yl]-6-(4-morpholinyl)-4-pyrimidinyl]amino}-1-piperidinecarboxylate (622 mg, 94%): mp 223-225° C.; 1H NMR (CDCl3) δ 7.92 (dd, J=8.4, 0.6 Hz, 1H), 7.54 (t, JHF=53.7 Hz, 1H), 7.32 (t, J=8.2 Hz, 1H), 6.79 (d, J=7.6 Hz, 1H), 4.68 (d, J=7.6 Hz, 1H), 4.23-4.10 (m, 3H), 4.05 (s, 3H), 3.89 (m, 4H), 3.25 (m, 4H), 3.06 (br s, 2H), 2.96 (t, J=12.0 Hz, 2H), 2.11 (m, 2H), 1.47 (s, 9H), 1.50-1.40 (m, 2H); Anal. Calcd. for C27H36F2N8O4: C, 56.4. H, 6.3; N, 19.5. Found: C, 56.3; H, 6.4; N, 19.7%.

Workup

  1. filtrationThe reaction mixture was filtered through celite
  2. washthe celite pad was washed with MeOH and CH2Cl2
  3. customthe solvents were removed under vacuum
  4. customRecrystallization from CH2Cl2/MeOH

Sources & evidence

ORD record
ord-9754f423d2c44d679374d3271e02ab63
Source dataset
uspto-grants-2015_08
Patent number
US09108980B2

Reaction notes

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