Triethylamine → HCID 69054647、化合物

HRID 731914ノート

反応式

HRID 731914 の反応式
[F:1][C:2]1[N:12]=[CH:11][C:5]2[N:6]=[CH:7][NH:8][C:9](=O)[C:4]=2[CH:3]=1.O=S(Cl)Cl.CCN(CC)CC.[C:24]([O:28][C:29](=[O:45])[C:30]1[CH:35]=[CH:34][CH:33]=[C:32]([O:36][C:37]2[CH:42]=[CH:41][C:40]([NH2:43])=[CH:39][C:38]=2[CH3:44])[CH:31]=1)([CH3:27])([CH3:26])[CH3:25]>ClCCCl.CN(C=O)C>[C:24]([O:28][C:29](=[O:45])[C:30]1[CH:35]=[CH:34][CH:33]=[C:32]([O:36][C:37]2[CH:42]=[CH:41][C:40]([NH:43][C:9]3[C:4]4[CH:3]=[C:2]([F:1])[N:12]=[CH:11][C:5]=4[N:6]=[CH:7][N:8]=3)=[CH:39][C:38]=2[CH3:44])[CH:31]=1)([CH3:27])([CH3:26])[CH3:25]

参加物

7

反応物 4

HCID 8471TriethylamineHCID 24386Thionyl ChlorideHCID 53439210tert-Butyl 3-(4-amino-2-methylphenoxy)benzoateHCID 1354173706-fluoropyrido[3,4-d]pyrimidin-4-ol

生成物 1

HCID 69054647HCID 69054647、化合物収率 80.8%

試薬・触媒・溶媒 2

HCID 111,2-Dichloroethane溶媒HCID 6228Dimethylformamide溶媒

実験手順

A solution of 6-Fluoro-3H-pyrido[3,4-d]pyrimidin-4-one (0.5 g, 3.05 mmol), SOCl2 (3.63 g, 30.5 mmol), and DMF (0.2 mL) in DCE (20 mL) was heated to reflux for 12 h. The reaction was then concentrated and the resulting dark residue was dissolved in t-BuOH/DCE 1:1 (20 mL), NEt3 (0.34 g, 3.36 mmol) and 3-(4-Amino-2-methyl-phenoxy)-benzoic acid tert-butyl ester (0.91 g, 3.05 mmol) were added, the resulting solution was heated to reflux for 5 h. The reaction was concentrated, the residue was dissolved in EtOAc and washed 2× water then the organic layer was dried over Na2SO4. Purification by flash column chromatography (Hexane/Ethyl Acetate 4:6) gave the title compound as a yellow solid (1.1 g, 80%). LRMS: 447.3/391.2 (MH+). 1H NMR (DMSO-d6, 400 MHz): δ 10.03 (s, 1H), δ 8.90 (s, 1H), δ 8.65 (s, 1H), δ 8.23 (s, 1H), δ 7.803 (d, 1H), δ 7.73 (dd, J=6.23, 2.49, 1H), δ 7.58 (d, 1H) δ 7.45 (t, J=7.89, 1H), δ 7.31-7.32 (m, 1H), δ 7.14-7.16 (m, 1H), δ 7.027 (d, J=8.72, 1H), δ 2.16 (s, 3H), δ 1.48 (s, 9H).

後処理

  1. temperatureto reflux for 12 h
  2. concentrationThe reaction was then concentrated
  3. dissolutionthe resulting dark residue was dissolved in t-BuOH/DCE 1:1 (20 mL)
  4. temperaturethe resulting solution was heated
  5. temperatureto reflux for 5 h
  6. concentrationThe reaction was concentrated
  7. dissolutionthe residue was dissolved in EtOAc
  8. washwashed 2× water
  9. dry with materialthe organic layer was dried over Na2SO4
  10. customPurification by flash column chromatography (Hexane/Ethyl Acetate 4:6)

出典と根拠

ORDレコード
ord-e099b3918245463d9336b4719e7a2c7e
出典データセット
uspto-grants-2009_09
特許番号
US07585869B2

反応ノート

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