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

HRID 926259ノート

反応式

HRID 926259 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]([C:18](=[O:28])[CH2:19][NH:20][C:21](OC(C)(C)C)=[O:22])[CH:7]2[CH2:13]C(OC)=O.BrC1C(F)=CC=C2C=1CCNC2CC(OC)=O.C(NCC(O)=O)(OC(C)(C)C)=O.C(N(CC)CC)C.Cl>CCOC(C)=O.C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC>[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:18](=[O:28])[CH2:19][NH:20][C:21](=[O:22])[CH:13]=[C:7]12

参加物

8

反応物 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 78288N-(tert-butoxycarbonyl)glycineHCID 86711336Methyl 2-(5-bromo-6-fluoro-1,2,3,4-tetrahydroisoquinolin-1-yl)acetateHCID 86711337Methyl 2-(5-bromo-2-(2-((tert-butoxycarbonyl)amino)acetyl)-6-fluoro-1,2,3,4-tetrahydroisoquinolin-1-yl)acetate

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 2

HCID 8857Ethyl Acetate溶媒2 回HCID 111923Propylphosphonic anhydride溶媒

実験手順

methyl 2-(5-bromo-2-(2-((tert-butoxycarbonyl)amino)acetyl)-6-fluoro-1,2,3,4-tetrahydroisoquinolin-1-yl)acetate. To a stirred solution of methyl 2-(5-bromo-6-fluoro-1,2,3,4-tetrahydroisoquinolin-1-yl)acetate (41.58 g, 138 mmol), Boc-glycine (26.5 g, 151 mmol) and triethylamine (38.4 mL, 275 mmol) in AcOEt (690 mL), T3P (98 mL, 165 mmol, 50% m/m in AcOEt) was added and the solution was stirred at RT for 1 h. 0.2N aqueous HCl (200 mL) was added and the reaction mixture was stirred for 5 min. The organic layer was separated and washed with 0.2N aqueous HCl (1×200 mL), saturated aqueous NaHCO3 (2×200 mL) and brine (1×200 mL). The combined organic layers were dried with sodium sulfate, filtered and the solvent was removed under reduced pressure. The residue was dried under high vacuo overnight to yield the title compound as white foam (62.6 g) which was used without further purification. UPLC-MS: MS 459.3/461.3 (M+H+); UPLC rt 1.13 min.

後処理

  1. stirringthe reaction mixture was stirred for 5 min
  2. customThe organic layer was separated
  3. washwashed with 0.2N aqueous HCl (1×200 mL), saturated aqueous NaHCO3 (2×200 mL) and brine (1×200 mL)
  4. dry with materialThe combined organic layers were dried with sodium sulfate
  5. filtrationfiltered
  6. customthe solvent was removed under reduced pressure
  7. customThe residue was dried under high vacuo overnight

出典と根拠

ORDレコード
ord-821e5755fa93425f83ed3db2ca296c9b
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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