Water → 9-Bromo-10-fluoro-3,4,7,8-tetrahydro-[1,4]diazepino[7,1-a]isoquinoline-2,5-dione

HRID 926262ノート

反応式

HRID 926262 の反応式
[Br:1][C:2]1[C:11]([F:12])=[CH:10][CH:9]=[C:8]2[C:3]=1[CH2:4][CH2:5][N:6]1[C:17](=[O:18])[CH2:16][NH:15][C:14](=[O:19])[CH2:13][CH:7]12.NCC(N1CCC2C(=CC=C(F)C=2Br)C1CC(O)=O)=O.C(N(CC)CC)C.O>C(Cl)Cl.C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC.CCOC(C)=O>[Br:1][C:2]1[C:11]([F:12])=[CH:10][CH:9]=[C:8]2[C:3]=1[CH2:4][CH2:5][N:6]1[C:17](=[O:18])[CH2:16][NH:15][C:14](=[O:19])[CH:13]=[C:7]12

参加物

8

反応物 4

HCID 962WaterHCID 8471TriethylamineHCID 867113392-(2-(2-aminoacetyl)-5-bromo-6-fluoro-1,2,3,4-tetrahydroisoquinolin-1-yl)acetic AcidHCID 867113409-Bromo-10-fluoro-1,3,4,7,8,12b-hexahydro-[1,4]diazepino[7,1-a]isoquinoline-2,5-dione

生成物 1

HCID 867113419-Bromo-10-fluoro-3,4,7,8-tetrahydro-[1,4]diazepino[7,1-a]isoquinoline-2,5-dione

試薬・触媒・溶媒 3

HCID 6344Dichloromethane溶媒HCID 8857Ethyl Acetate溶媒HCID 111923Propylphosphonic anhydride溶媒

実験手順

9-bromo-10-fluoro-1,3,4,7,8,12b-hexahydro-[1,4]diazepino[7,1-a]isoquinoline-2,5-dione. To a stirred solution of 2-(2-(2-aminoacetyl)-5-bromo-6-fluoro-1,2,3,4-tetrahydroisoquinolin-1-yl)acetic acid (HCl salt) (54.6 g, 143 mmol) and triethylamine (100 mL, 715 mmol) in DCM (570 mL), T3P (125 mL, 215 mmol, 50% m/m in AcOEt) was added slowly (exotherm) and the suspension was stirred at rt for 1 h. The solvent was reduced to a small amount under reduced pressure and the thick suspension was treated with water (500 mL) and the suspension was stirred overnight. The suspension was filtered off and the solid was again treated with water (200 mL), stirred for 10 min and filtered off. The slightly yellow solid was washed with water (1×) and with diethyl ether (2×). The resulting solid was dried at rt under high vacuo overnight to yield the title compound as slightly yellow solid (40.5 g). UPLC-MS: MS 327.1/329.1 (M+H+); UPLC rt 0.73 min.

後処理

  1. stirringthe suspension was stirred overnight
  2. filtrationThe suspension was filtered off
  3. additionthe solid was again treated with water (200 mL)
  4. stirringstirred for 10 min
  5. filtrationfiltered off
  6. washThe slightly yellow solid was washed with water (1×) and with diethyl ether (2×)
  7. customThe resulting solid was dried at rt under high vacuo overnight

出典と根拠

ORDレコード
ord-e31a0bbf516e4a0bbf692dc3cb50a799
出典データセット
uspto-grants-2016_03
特許番号
US09284331B2

反応ノート

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