2-Aminopyrimidine → HCID 58102786, compound

HRID 450155Notes

Reaction equation

HRID 450155 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][CH: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[N:7]=[CH:6][CH: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 79782-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 58102786HCID 58102786, compoundYield 31%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 0.214 g (2.25 mmol) of 2-aminopyrimidine in THF (4 mL) at 0° C. was added 1.25 mL of NaHMDS (2 M solution in THF) and the mixture was stirred for 20 min. A solution of 0.275 g (0.75 mmol) of 1-[4-chloro-6-(4-morpholinyl)-1,3,5-triazin-2-yl]-2-(difluoromethyl)-1H-benzimidazole in THF (4 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 first with hexanes/EtOAc (4:1), then with CH2Cl2/EtOAc (1:3) gave an orange powder. Recrystallization from ethanol gave 0.098 g (31% yield) of 4-[2-(difluoromethyl)-1H-benzimidazol-1-yl]-6-(4-morpholinyl)-N-(2-pyrimidinyl)-1,3,5-triazin-2-amine: mp 261-263° C.; 1H NMR (CDCl3) δ8.69-8.67 (m, 3H), 8.34 (t, JHF=53.3 Hz, 1H), 8.07 (br s, 1H), 7.91 (dd, J=7.9, 0.9 Hz, 1H), 7.49-7.40 (m, 2H), 7.05 (t, J=4.8 Hz, 1H), 3.96 (m, 4H), 3.83 (m, 4H); Anal. Calcd. for C19H17F2N9O: C, 53.65; H, 4.0; N, 29.6. Found: C, 53.6; H, 4.1; 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 first with hexanes/EtOAc (4:1)
  7. customwith CH2Cl2/EtOAc (1:3) gave an orange powder
  8. customRecrystallization from ethanol

Sources & evidence

ORD record
ord-7f369f625fce4c3188e2f3f1cd3ddfb5
Source dataset
uspto-grants-2013_07
Patent number
US08486939B2

Reaction notes

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