1-Hydroxybenzotriazole → N-[4'-({[(1-t-Butyloxycarbonylpiperidin-4-yl)methyl]amino}carbonyl)-6-methyl-1,1'-biphenyl-3-yl]-3-furamide

HRID 970228노트

반응식

HRID 970228 반응식
[O:1]1[CH:5]=[CH:4][C:3]([C:6]([NH:8][C:9]2[CH:10]=[CH:11][C:12]([CH3:24])=[C:13]([C:15]3[CH:20]=[CH:19][C:18]([C:21](O)=[O:22])=[CH:17][CH:16]=3)[CH:14]=2)=[O:7])=[CH:2]1.[C:25]([O:29][C:30]([N:32]1[CH2:37][CH2:36][CH:35]([CH2:38][NH2:39])[CH2:34][CH2:33]1)=[O:31])([CH3:28])([CH3:27])[CH3:26].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>CN(C=O)C.C(OCC)(=O)C>[C:25]([O:29][C:30]([N:32]1[CH2:37][CH2:36][CH:35]([CH2:38][NH:39][C:21]([C:18]2[CH:17]=[CH:16][C:15]([C:13]3[C:12]([CH3:24])=[CH:11][CH:10]=[C:9]([NH:8][C:6]([C:3]4[CH:4]=[CH:5][O:1][CH:2]=4)=[O:7])[CH:14]=3)=[CH:20][CH:19]=2)=[O:22])[CH2:34][CH2:33]1)=[O:31])([CH3:28])([CH3:27])[CH3:26]

참가 물질

8

반응물 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 7368171-Boc-4-(aminomethyl)piperidineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 691521465'-(3-Furoylamino)-2'-methyl-1,1'-biphenyl-4-carboxylic acid

생성물 1

HCID 69152270N-[4'-({[(1-t-Butyloxycarbonylpiperidin-4-yl)methyl]amino}carbonyl)-6-methyl-1,1'-biphenyl-3-yl]-3-furamide

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

5′-(3-Furoylamino)-2′-methyl-1,1′-biphenyl-4-carboxylic acid (50 mg, 0.156 mmol), 1-t-butyloxycarbonyl-4-aminomethylpiperidine (33.3 mg, 0.156 mmol), HATU (59.2 mg, 0.156 mmol), HOBT (21 mg, 0.156 mmol) and DIPEA (27 μL, 0.156 mmol) in DMF (2 ml) were stirred at room temperature for 18 h. The reaction was diluted with ethyl acetate (150 ml), washed with water (2×30 ml) and dried (magnesium sulphate). The solvent was evaporated under vacuum and the residue chromatographed on a silica flash column eluting with DCM/methanol/triethylamine (96:2:2). Concentration of the product fractions under vacuum N-[4′-({[(1-t-butyloxycarbonylpiperidin-4-yl)methyl]amino}carbonyl)-6-methyl-1,1′-biphenyl-3-yl]-3-furamide (45 mg, 56%). NMR; δH [2H6]-DMSO 9.91,(1H, s), 8.56,(1H, t), 8.35,(1H, s), 7.91,(2H, d), 7.78,(1H, t), 7.66,(1H, dd), 7.59,(1H, d), 7.43,(2H, d), 7.27,(1H, d), 6.98,(1H, m), 3.93,(2H, m), 3.17,(2H, t), 2.68,(2H, b), 2.19,(3H, s), 1.74,(1H, b), 1.67,(2H, m), 1.38,(9H, s), 1.03,(2H, m). LCMS: retention time 3.50 min, [MH-BOC]+418.

후처리

  1. washwashed with water (2×30 ml)
  2. dry with materialdried (magnesium sulphate)
  3. customThe solvent was evaporated under vacuum
  4. customthe residue chromatographed on a silica flash column
  5. washeluting with DCM/methanol/triethylamine (96:2:2)

출처 및 근거

ORD 기록
ord-446310f9fad4413c915e3d8f1f02f6a4
출처 데이터셋
uspto-grants-2007_12
특허 번호
US07309800B2

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