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 1808916ノート

反応式

HRID 1808916 の反応式
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

参加物

6

反応物 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

生成物 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

試薬・触媒・溶媒 1

HCID 1140Toluene溶媒

反応条件

温度
130 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-3c7a075b926d46caa0b6d59396ef0f44
出典データセット
uspto-grants-2013_01
特許番号
US08362009B2

反応ノート

読み込み中…