Triethylamine → ethyl 1'-{(R)-3-(4-benzyloxy-3,5-dimethyl-phenyl)-2-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carbonyloxy]-propionyl}-1,4'-bipiperidinyl-4-carboxylate

HRID 599773노트

반응식

HRID 599773 반응식
[O:1]=[C:2]1[N:8]([CH:9]2[CH2:14][CH2:13][N:12]([C:15]([O:17][C@@H:18]([C:36](O)=[O:37])[CH2:19][C:20]3[CH:25]=[C:24]([CH3:26])[C:23]([O:27][CH2:28][C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=4)=[C:22]([CH3:35])[CH:21]=3)=[O:16])[CH2:11][CH2:10]2)[CH2:7][CH2:6][C:5]2[CH:39]=[CH:40][CH:41]=[CH:42][C:4]=2[NH:3]1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C(N(CC)CC)C.[CH2:72]([O:74][C:75]([CH:77]1[CH2:82][CH2:81][N:80]([CH:83]2[CH2:88][CH2:87][NH:86][CH2:85][CH2:84]2)[CH2:79][CH2:78]1)=[O:76])[CH3:73]>C1COCC1.CCOC(C)=O>[CH2:28]([O:27][C:23]1[C:24]([CH3:26])=[CH:25][C:20]([CH2:19][C@@H:18]([O:17][C:15]([N:12]2[CH2:11][CH2:10][CH:9]([N:8]3[CH2:7][CH2:6][C:5]4[CH:39]=[CH:40][CH:41]=[CH:42][C:4]=4[NH:3][C:2]3=[O:1])[CH2:14][CH2:13]2)=[O:16])[C:36]([N:86]2[CH2:87][CH2:88][CH:83]([N:80]3[CH2:81][CH2:82][CH:77]([C:75]([O:74][CH2:72][CH3:73])=[O:76])[CH2:78][CH2:79]3)[CH2:84][CH2:85]2)=[O:37])=[CH:21][C:22]=1[CH3:35])[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1

참가 물질

7

반응물 4

HCID 8471Triethylamine2회HCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 4778238[1,4']Bipiperidinyl-4-carboxylic acid ethyl esterHCID 25208036(R)-2-(4-benzyloxy-3,5-dimethyl-phenyl)-1-carboxy-ethyl 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylate

생성물 1

HCID 67273670ethyl 1'-{(R)-3-(4-benzyloxy-3,5-dimethyl-phenyl)-2-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carbonyloxy]-propionyl}-1,4'-bipiperidinyl-4-carboxylate

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매

실험 절차

A solution of 400 mg (0.70 mmol) (R)-2-(4-benzyloxy-3,5-dimethyl-phenyl)-1-carboxy-ethyl 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylate (Example 1g), 250 mg (0.78 mmol) TBTU and 0.12 mL (3.73 mmol) triethylamine in 20 mL THF were stirred for 1 h at RT. Then 0.4 mL (2.87 mmol) triethylamine and 270 mg (0.86 mmol) ethyl[1,4′]bipiperidinyl-4-carboxylate (used as the bis-hydrochloride salt) were added. The reaction mixture was stirred for 24 h at RT, diluted with EtOAc, washed with saturated NaHCO3 solution and the organic phase was dried on Na2SO4. After the elimination of the desiccant and solvent the residue was purified by chromatography (Alox activity stage II-III, gradient DCM/EtOH 40:1 to DCM/EtOH 30:1).

후처리

  1. additionwere added
  2. washwashed with saturated NaHCO3 solution
  3. customthe organic phase was dried on Na2SO4
  4. customAfter the elimination of the desiccant and solvent the residue was purified by chromatography (Alox activity stage II-III, gradient DCM/EtOH 40:1 to DCM/EtOH 30:1)

출처 및 근거

ORD 기록
ord-e2ce0396695e4975b1a8728d7d32ccb3
출처 데이터셋
uspto-grants-2011_03
특허 번호
US07897603B2

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