Triethylamine → 2-{6,7-dimethyl-4-[5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoyl]-1,4-diazepan-1-yl}-6-fluoroquinazoline

HRID 1808916Notes

Reaction equation

HRID 1808916 reaction equation
Cl.[CH3:2][CH:3]1[CH:9]([CH3:10])[CH2:8][N:7]([C:11](=[O:24])[C:12]2[CH:17]=[C:16]([CH3:18])[CH:15]=[CH:14][C:13]=2[N:19]2[N:23]=[CH:22][CH:21]=[N:20]2)[CH2:6][CH2:5][NH:4]1.Cl[C:26]1[N:35]=[CH:34][C:33]2[C:28](=[CH:29][CH:30]=[C:31]([F:36])[CH:32]=2)[N:27]=1.C(N(CC)CC)C.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1>[CH3:10][CH:9]1[CH:3]([CH3:2])[N:4]([C:26]2[N:35]=[CH:34][C:33]3[C:28](=[CH:29][CH:30]=[C:31]([F:36])[CH:32]=3)[N:27]=2)[CH2:5][CH2:6][N:7]([C:11](=[O:24])[C:12]2[CH:17]=[C:16]([CH3:18])[CH:15]=[CH:14][C:13]=2[N:19]2[N:23]=[CH:22][CH:21]=[N:20]2)[CH2:8]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 179135522-Chloro-6-fluoroquinazolineHCID 685121195,6-dimethyl-1-[5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoyl]-1,4-diazepane hydrochloride

Product 1

HCID 252562522-{6,7-dimethyl-4-[5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoyl]-1,4-diazepan-1-yl}-6-fluoroquinazoline

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
130 °C

Procedure

Compound 1-7 (75 mg, 0.21 mmol) was combined with 2-chloro-6-fluoroquinazoline 1-8 (39 mg, 0.21 mmol; see example 1-D), triethylamine (30 uL, 0.21 mmol), and potassium carbonate (296 mg, 2.1 mmol) in toluene (2 mL) and heated in a sealed tube to 130° C. overnight. The reaction was concentrated in vacuo and the residue purified by reverse phase preparative chromatography on a C-18 column (5 to 75% acetonitrile in water with 0.1% TFA buffer). The clean fractions were combined and made basic with 20% sodium carbonate solution. This was extracted with ethyl acetate two times and the combined organics washed with brine and dried with sodium sulfate. Concentration in vacuo gave the titled compound as a solid. Data for 1-9: LC/MS: m/z (M+Na)=460.2 found; 460.5 calculated.

Workup

  1. concentrationThe reaction was concentrated in vacuo
  2. customthe residue purified by reverse phase preparative chromatography on a C-18 column (5 to 75% acetonitrile in water with 0.1% TFA buffer)
  3. extractionThis was extracted with ethyl acetate two times
  4. washthe combined organics washed with brine
  5. dry with materialdried with sodium sulfate
  6. concentrationConcentration in vacuo

Sources & evidence

ORD record
ord-3c7a075b926d46caa0b6d59396ef0f44
Source dataset
uspto-grants-2013_01
Patent number
US08362009B2

Reaction notes

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