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 1808916노트

반응식

HRID 1808916 반응식
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

참가 물질

6

반응물 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

생성물 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

시약·촉매·용매 1

HCID 1140Toluene용매

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온도
130 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-3c7a075b926d46caa0b6d59396ef0f44
출처 데이터셋
uspto-grants-2013_01
특허 번호
US08362009B2

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