1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → Benzyl 3-[(4-cyclobutyl-1,4-diazepan-1-yl)carbonyl]azetidine-1-carboxylate

HRID 1402729ノート

反応式

HRID 1402729 の反応式
[CH2:1]([O:8][C:9]([N:11]1[CH2:14][CH:13]([C:15]([OH:17])=O)[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.[CH:39]1([N:43]2[CH2:49][CH2:48][CH2:47][NH:46][CH2:45][CH2:44]2)[CH2:42][CH2:41][CH2:40]1>CN(C=O)C.C(Cl)Cl.C(Cl)Cl>[CH:39]1([N:43]2[CH2:49][CH2:48][CH2:47][N:46]([C:15]([CH:13]3[CH2:12][N:11]([C:9]([O:8][CH2:1][C:2]4[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=4)=[O:10])[CH2:14]3)=[O:17])[CH2:45][CH2:44]2)[CH2:42][CH2:41][CH2:40]1

参加物

7

反応物 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 109882141-[(Benzyloxy)carbonyl]azetidine-3-carboxylic acidHCID 574239531-Cyclobutyl-[1,4]diazepane

生成物 1

HCID 46843044Benzyl 3-[(4-cyclobutyl-1,4-diazepan-1-yl)carbonyl]azetidine-1-carboxylate収率 60%

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒HCID 22350042dichloromethane N,N-dimethylformamide溶媒

実験手順

To a stirred solution of 1-[(benzyloxy)carbonyl]azetidine-3-carboxylic acid (500 mg, 2.13 mmol) in DMF/DCM (1:10) (11 ml) was added HOBt (287 mg, 2.13 mmol) and EDCI (490 mg, 2.56 mmol). The resulting suspension was stirred at RT for 10 mins before dropwise addition of 1-cyclobutyl-1,4-diazepane (328 mg, 2.13 mmol) in DCM (3 ml). After stirring for 16 h at RT the reaction was shown to be complete by TLC and the solvent was evaporated at reduced pressure. The residue was treated with saturated aqueous NaHCO3 (10 ml) and the resulting aqueous extracted with EtOAc (3×7.5 ml). The combined organic phases were dried (MgSO4), filtered and concentrated at reduced pressure. Purification by silica FCC (eluting with 99:1 to 97:3 gradient of DCM/2M NH3 in MeOH) provided the title compound (475 mg, 60% yield) as a yellow oil.

後処理

  1. customthe solvent was evaporated at reduced pressure
  2. additionThe residue was treated with saturated aqueous NaHCO3 (10 ml)
  3. extractionthe resulting aqueous extracted with EtOAc (3×7.5 ml)
  4. dry with materialThe combined organic phases were dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated at reduced pressure
  7. customPurification
  8. washby silica FCC (eluting with 99:1 to 97:3 gradient of DCM/2M NH3 in MeOH)

出典と根拠

ORDレコード
ord-928d3fa4785047bd9ce6e9f26b51c278
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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