Acetic Acid → HCID 58102784, compound

HRID 450154Notes

Reaction equation

HRID 450154 reaction equation
[NH2:1][C:2]1[CH:3]=[N:4][C:5]2[C:10]([CH:11]=1)=[CH:9][CH:8]=[CH:7][CH:6]=2.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].Cl[C:23]1[N:28]=[C:27]([N:29]2[CH2:34][CH2:33][O:32][CH2:31][CH2:30]2)[N:26]=[C:25]([N:35]2[C:39]3[CH:40]=[CH:41][CH:42]=[CH:43][C:38]=3[N:37]=[C:36]2[CH:44]([F:46])[F:45])[N:24]=1.C(O)(=O)C>C1COCC1.O>[F:46][CH:44]([F:45])[C:36]1[N:35]([C:25]2[N:26]=[C:27]([N:29]3[CH2:30][CH2:31][O:32][CH2:33][CH2:34]3)[N:28]=[C:23]([NH:1][C:2]3[CH:3]=[N:4][C:5]4[C:10]([CH:11]=3)=[CH:9][CH:8]=[CH:7][CH:6]=4)[N:24]=2)[C:39]2[CH:40]=[CH:41][CH:42]=[CH:43][C:38]=2[N:37]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 113753-AminoquinolineHCID 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 58102784HCID 58102784, compoundYield 46%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 0.323 g (2.24 mmol) of 3-aminoquinoline in THF (5 mL) at 0° C. was added 1.6 mL of NaHMDS (2 M solution in THF), and the mixture was stirred for 15 min. A solution of 0.280 g (0.77 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. The resulting mixture was neutralized with acetic acid, 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 (1:1), and then CH2Cl2-EtOAc (1:3) gave a pink powder. Recrystallization from ethanol gave 0.167 g (46% yield) of N-[4-[2-(difluoromethyl)-1H-benzimidazol-1-yl]-6-(4-morpholinyl)-1,3,5-triazin-2-yl]-3-quinolinamine: mp 270-273° C.; 1H NMR (CDCl3) δ 9.08 (br s, 1H), 8.48-8.43 (m, 2H), 8.12 (d, J=8.4 Hz, 1H), 7.93-7.90 (m, 1H), 7.80 (dd, J=8.0, 1.1 Hz, 1H), 7.69 (dt, J=6.9, 1.4 Hz, 1H), 7.61-7.41 (m, 4 H), 7.30 (d, J=5.3 Hz, 1H), 3.97-3.95 (m, 4H), 3.83 (s, 4H); Anal. Calcd. for C24H20F2N8O: C, 60.75; H, 4.3; N, 23.6. Found: C, 60.7; H, 4.2; N, 23.5%.

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 (1:1)
  7. customCH2Cl2-EtOAc (1:3) gave a pink powder
  8. customRecrystallization from ethanol

Sources & evidence

ORD record
ord-11db20ccadd540c88ded204aea371801
Source dataset
uspto-grants-2013_07
Patent number
US08486939B2

Reaction notes

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