Thionyl Chloride → Tert-butyl 4-({1-[(benzyloxy)carbonyl]azetidin-3-yl}carbonyl)-1,4-diazepane-1-carboxylate

HRID 1402753ノート

反応式

HRID 1402753 の反応式
C1(N2CCCN([C:12]([CH:14]3[CH2:17][N:16]([C:18]([O:20][CH2:21][C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)=[O:19])[CH2:15]3)=[O:13])CC2)CCC1.O=S(Cl)Cl.[N:32]1([C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[CH2:38][CH2:37][CH2:36][NH:35][CH2:34][CH2:33]1.CCN(C(C)C)C(C)C>C(Cl)Cl>[CH2:21]([O:20][C:18]([N:16]1[CH2:17][CH:14]([C:12]([N:35]2[CH2:36][CH2:37][CH2:38][N:32]([C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[CH2:33][CH2:34]2)=[O:13])[CH2:15]1)=[O:19])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1

参加物

6

反応物 4

HCID 24386Thionyl Chloride2 回HCID 81531DiisopropylethylamineHCID 2756058Tert-butyl 1,4-diazepane-1-carboxylateHCID 46843044Benzyl 3-[(4-cyclobutyl-1,4-diazepan-1-yl)carbonyl]azetidine-1-carboxylate

生成物 1

HCID 66739816Tert-butyl 4-({1-[(benzyloxy)carbonyl]azetidin-3-yl}carbonyl)-1,4-diazepane-1-carboxylate収率 86.8%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

To a stirred solution of benzyl 3-[(4-cyclobutyl-1,4-diazepan-1-yl)carbonyl]azetidine-1-carboxylate (1.0 g, 4.25 mmol) in DCM (20 mL) was added SOCl2 (0.754 g, 0.460 mL, 6.38 mmol) and the resulting mixture was stirred for 2 hours at room temperature. LCMS analysis showed incomplete conversion so a further 1.0 eq of SOCl2 (501 mg, 305 μL) was added and the reaction stirred for a further 19 hours. Volatiles were removed at reduced pressure and the crude acid chloride dissolved in DCM (10 mL) and added dropwise to a solution of tert-butyl 1,4-diazepane-1-carboxylate (0.658 g, 5.10 mmol, 1.2 eq) and DIPEA (1.67 g, 12.75 mmol, 3.0 eq) in DCM (10 mL) at 0° C. The resulting solution was stirred at room temperature for 17 hours and then quenched by addition of NaHCO3 (5 mL). The reaction was diluted with DCM (10 mL) and the phases separated. The organic was washed with brine (5 mL), dried (MgSO4), filtered and concentrated at reduced pressure. Purification by silica FCC (eluting with 98:1.2:0.8 to 97:2.7:0.3 gradient of DCM/MeOH/NH3) gave the title compound (1.54 g, 86%).

後処理

  1. additionwas added
  2. stirringthe reaction stirred for a further 19 hours
  3. customVolatiles were removed at reduced pressure
  4. dissolutionthe crude acid chloride dissolved in DCM (10 mL)
  5. stirringThe resulting solution was stirred at room temperature for 17 hours
  6. customquenched by addition of NaHCO3 (5 mL)
  7. additionThe reaction was diluted with DCM (10 mL)
  8. customthe phases separated
  9. washThe organic was washed with brine (5 mL)
  10. dry with materialdried (MgSO4)
  11. filtrationfiltered
  12. concentrationconcentrated at reduced pressure
  13. customPurification
  14. washby silica FCC (eluting with 98:1.2:0.8 to 97:2.7:0.3 gradient of DCM/MeOH/NH3)

出典と根拠

ORDレコード
ord-34fae5604aff42868d7102440a109325
出典データセット
uspto-grants-2014_12
特許番号
US08912176B2

反応ノート

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