Toluene → 4-(6,7-Dimethoxy-quinazolin-4-yl)-piperidine-1-carbonyl chloride

HRID 657188

反応式

HRID 657188 の反応式
[C:1]([Cl:4])(Cl)=[O:2].C1(C)C=CC=CC=1.[CH3:12][O:13][C:14]1[CH:15]=[C:16]2[C:21](=[CH:22][C:23]=1[O:24][CH3:25])[N:20]=[CH:19][N:18]=[C:17]2[CH:26]1[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]1.CCN(C(C)C)C(C)C.C([O-])(=O)CC(CC([O-])=O)(C([O-])=O)O.[Na+].[Na+].[Na+]>C(Cl)Cl>[CH3:12][O:13][C:14]1[CH:15]=[C:16]2[C:21](=[CH:22][C:23]=1[O:24][CH3:25])[N:20]=[CH:19][N:18]=[C:17]2[CH:26]1[CH2:31][CH2:30][N:29]([C:1]([Cl:4])=[O:2])[CH2:28][CH2:27]1

参加物

7

反応物 5

HCID 1140TolueneHCID 6224Trisodium citrateHCID 6371PhosgeneHCID 81531DiisopropylethylamineHCID 595517346,7-Dimethoxy-4-(piperidin-4-yl)quinazoline

生成物 1

HCID 587707144-(6,7-Dimethoxy-quinazolin-4-yl)-piperidine-1-carbonyl chloride収率 51%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

To a −78° C. solution of 1.85 M phosgene in toluene (15.8 mL, 29.3 mmol) and DCM (32 mL) was added 6,7-dimethoxy-4-piperidin-4-yl-quinazoline (4.00 g, 14.6 mmol), prepared as described in Example 1d, in one portion with stirring, followed immediately by the rapid addition of DIEA (2.66 mL, 16.1 mmol) along the walls of the flask over ˜5 sec. The flask was sealed and stirred at −78° C. for another 5 min before placing the flask in an ice bath with stirring at 0° C. for 30 min. The opaque easily stirred slurry was then poured into a mixture of DCM (70 mL), 0.5 M trisodium citrate (60 mL), and ice (60 mL), and partitioned. The aqueous layer was extracted with DCM (1×50 mL) and the organic layers combined, dried (Na2SO4), and concentrated under reduced pressure to give the crude title compound as an orange solid. Purification by flash chromatography (7:1→4:1 DCM/acetone) afforded the title compound as a beige solid (2.50 g, 51%). 1H-NMR (300 MHz, CDCl3) 9.07 (s, 1H), 7.35 (s, 1H), 7.23 (s, 1H), 4.58-4.47 (m, 2H), 4.072 (s, 3H), 4.068 (s, 3H), 3.65 (tt, J=10.9 Hz, 4.0 Hz, 1H), 3.46-3.33 (m, 1H), 3.28-3.14 (m, 1H), 2.30-2.06 (m, 2H), 2.06-1.95 (m, 2H). LC/MS (ESI): calcd mass 335.1, found 336.1 (MH)+.

後処理

  1. customprepared
  2. customThe flask was sealed
  3. stirringstirred at −78° C. for another 5 min
  4. stirringwith stirring at 0° C. for 30 min
  5. custompartitioned
  6. extractionThe aqueous layer was extracted with DCM (1×50 mL)
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated under reduced pressure
  9. customto give the crude title compound as an orange solid
  10. customPurification by flash chromatography (7:1→4:1 DCM/acetone)

出典と根拠

ORDレコード
ord-f75f36d1dfc74616a47209bd80938edf
出典データセット
uspto-grants-2011_12
特許番号
US08071768B2

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