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 599773ノート

反応式

HRID 599773 の反応式
[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

参加物

7

反応物 4

HCID 8471Triethylamine2 回HCID 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

生成物 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

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-e2ce0396695e4975b1a8728d7d32ccb3
出典データセット
uspto-grants-2011_03
特許番号
US07897603B2

反応ノート

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