Dimethylamine → 4-(benzyloxy)-1-(2-(2-(dimethylamino)acetyl)-5-methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indol-7-yl)pyridin-2(1H)-one

HRID 1020544ノート

反応式

HRID 1020544 の反応式
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][N:12]([C:15]2[CH:16]=[CH:17][C:18]3[C:19]4[CH2:28][NH:27][CH2:26][CH2:25][C:20]=4[N:21]([CH3:24])[C:22]=3[CH:23]=2)[C:11](=[O:29])[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl[CH2:31][C:32](Cl)=[O:33].C[CH2:36][N:37](CC)[CH2:38]C.N(C)C.C([O-])([O-])=O.[K+].[K+]>C(Cl)Cl.CN(C=O)C>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][N:12]([C:15]2[CH:16]=[CH:17][C:18]3[C:19]4[CH2:28][N:27]([C:32](=[O:33])[CH2:31][N:37]([CH3:38])[CH3:36])[CH2:26][CH2:25][C:20]=4[N:21]([CH3:24])[C:22]=3[CH:23]=2)[C:11](=[O:29])[CH:10]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

参加物

8

反応物 5

HCID 674DimethylamineHCID 6577Chloroacetyl chlorideHCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 44123851HCID 44123851、化合物

生成物 1

HCID 441950374-(benzyloxy)-1-(2-(2-(dimethylamino)acetyl)-5-methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indol-7-yl)pyridin-2(1H)-one収率 51%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒

実験手順

To a solution of 4-benzyloxy-1-(5-methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indol-7-yl)pyridin-2(1H)-one (100 mg, 0.26 mmol) in CH2Cl2 (2 mL) was added 2-chloroacetyl chloride (29 μL, 0.36 mmol) and Et3N (0.1 mL, 0.7 mmol). The reaction mixture was stirred at room temperature until the reaction was complete. After the solvent was removed, the residue was dissolved in DMF. To the DMF solution was added (CH3)2NH (64 μL, 1.2 mmol) and K2CO3 (166 mg, 1.2 mmol). The reaction mixture was heated to 70° C. and stirred at 70° C. until the reaction was complete. After it was cooled, the reaction was quenched with water and extracted with CH2Cl2. The organic layer was washed with H2O and 5% LiCl, dried with Na2SO4, filtered, and concentrated. Purification by flash column chromatography (silica gel, 10% CH3OH in CH2Cl2) gave 4-(benzyloxy)-1-(2-(2-(dimethylamino)acetyl)-5-methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indol-7-yl)pyridin-2(1H)-one (58 mg, 51%) as a yellow foam. The free base was converted to the HCl salt to give the title compound (31 mg, 50%) as a yellow solid and as a mixture of rotamers: mp 135-140° C.; 1H NMR (500 MHz, CD3OD) δ 7.75-7.71 (m, 1H), 7.59-7.55 (m, 1H), 7.49-7.37 (m, 6H), 7.05-7.01 (m, 1H), 6.49-6.45 (m, 1H), 6.28-6.26 (m, 1H), 5.24 (s, 2H), 4.87 (br s, 1H), 4.69 (br s, 1H), 4.44-4.41 (m, 2H), 4.11-4.07 (m, 1H), 3.85-3.82 (m, 1H), 3.70 (2×s, 3H), 3.06-2.92 (m, 2H), 2.97-2.94 (2×s, 6H); ESI MS m/z 471 [M+H]+; HPLC (Method B) 97.0% (AUC), tR=13.2 min.

後処理

  1. customAfter the solvent was removed
  2. dissolutionthe residue was dissolved in DMF
  3. temperatureThe reaction mixture was heated to 70° C.
  4. stirringstirred at 70° C. until the reaction
  5. temperatureAfter it was cooled
  6. customthe reaction was quenched with water
  7. extractionextracted with CH2Cl2
  8. washThe organic layer was washed with H2O and 5% LiCl
  9. dry with materialdried with Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customPurification by flash column chromatography (silica gel, 10% CH3OH in CH2Cl2)

出典と根拠

ORDレコード
ord-f5d7e68432b64ace9ec351c934516c86
出典データセット
uspto-grants-2014_05
特許番号
US08716308B2

反応ノート

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