4-Aminopyrimidine → HCID 58102797, compound

HRID 450156Notes

Reaction equation

HRID 450156 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][N:5]=[CH:4][N:3]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].Cl[C:19]1[N:24]=[C:23]([N:25]2[CH2:30][CH2:29][O:28][CH2:27][CH2:26]2)[N:22]=[C:21]([N:31]2[C:35]3[CH:36]=[CH:37][CH:38]=[CH:39][C:34]=3[N:33]=[C:32]2[CH:40]([F:42])[F:41])[N:20]=1>C1COCC1.C(O)(=O)C.O>[F:42][CH:40]([F:41])[C:32]1[N:31]([C:21]2[N:22]=[C:23]([N:25]3[CH2:26][CH2:27][O:28][CH2:29][CH2:30]3)[N:24]=[C:19]([NH:1][C:2]3[CH:7]=[CH:6][N:5]=[CH:4][N:3]=3)[N:20]=2)[C:35]2[CH:36]=[CH:37][CH:38]=[CH:39][C:34]=2[N:33]=1

Participants

7

Reactant 3

HCID 689584-AminopyrimidineHCID 2724254Sodium bis(trimethylsilyl)amideHCID 220368724-(4-chloro-6-(2-(difluoromethyl)-1H-benzo[d]imidazol-1-yl)-1,3,5-triazin-2-yl)morpholine

Product 1

HCID 58102797HCID 58102797, compoundYield 6.1%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 0.214 g (2.25 mmol) of 4-aminopyrimidine in THF (4.5 mL) at 0° C. was added 1.25 mL of NaHMDS (2 M solution in THF), and the mixture stirred for 20 min. A solution of 0.282 g (0.77 mmol) of 1-[4-chloro-6-(4-morpholinyl)-1,3,5-triazin-2-yl]-2-(difluoromethyl)-1H-benzimidazole in THF (6 mL) was added and the resulting mixture was stirred for 1 hr at RT. After neutralization with acetic acid, the mixture was diluted with water and extracted with EtOAc. The organic layer was washed sequentially with water and aq. NH3, dried and concentrated. Chromatography on alumina, eluting with CH2Cl2/EtOAc (1:3) gave a white powder. Recrystallization from ethanol gave 0.020 g (6% yield) of 4-[2-(difluoromethyl)-1H-benzimidazol-1-yl]-6-(4-morpholinyl)-N-(4-pyrimidinyl)-1,3,5-triazin-2-amine: mp 233-235° C.; 1H NMR (CDCl3) δ8.92 (d, J=1.4 Hz, 1H), 8.67 (d, J=5.8 Hz, 1H), 8.39 (dd, J=6.8, 1.7 Hz, 1H), 8.22 (dd, J=5.8, 1.3 Hz, 1H), 8.01 (s, 1H), 7.92 (dd, J=6.8, 1.7 Hz, 1H), 7.56 (t, JHF=53.5 Hz, 1H), 7.49-7.43 (m, 2H), 3.98-3.96 (m, 4H), 3.86-3.85 (m, 4H); Anal. Calcd. for C19H17F2N9O: C, 53.65; H, 4.1; N, 29.6. Found: C, 53.35; H, 4.2; N, 29.4%.

Workup

  1. stirringthe resulting mixture was stirred for 1 hr at RT
  2. extractionextracted with EtOAc
  3. washThe organic layer was washed sequentially with water and aq. NH3
  4. customdried
  5. concentrationconcentrated
  6. washChromatography on alumina, eluting with CH2Cl2/EtOAc (1:3)
  7. customgave a white powder
  8. customRecrystallization from ethanol

Sources & evidence

ORD record
ord-db96854fb83a4d459743d5bae577ff13
Source dataset
uspto-grants-2013_07
Patent number
US08486939B2

Reaction notes

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