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Methanol → 3-({1-[1-(4-Chloro-3-methyl-benzyl)-piperidin-4-yl]-5-oxo-pyrrolidine-2-carbonyl}-amino)-5-(1-methyl-1H-tetrazol-5-yl)-benzoic acid methyl ester

HRID 2059644
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HRID 2059644 반응식
Br[C:2]1[CH:3]=[C:4]([NH:14][C:15]([CH:17]2[CH2:21][CH2:20][C:19](=[O:22])[N:18]2[CH:23]2[CH2:28][CH2:27][N:26]([CH2:29][C:30]3[CH:35]=[CH:34][C:33]([Cl:36])=[C:32]([CH3:37])[CH:31]=3)[CH2:25][CH2:24]2)=[O:16])[CH:5]=[C:6]([C:8]2[N:12]([CH3:13])[N:11]=[N:10][N:9]=2)[CH:7]=1.C(N(CC)CC)C.CN([CH:48]=[O:49])C.[CH3:50][OH:51]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:50][O:51][C:48](=[O:49])[C:2]1[CH:7]=[C:6]([C:8]2[N:12]([CH3:13])[N:11]=[N:10][N:9]=2)[CH:5]=[C:4]([NH:14][C:15]([CH:17]2[CH2:21][CH2:20][C:19](=[O:22])[N:18]2[CH:23]2[CH2:28][CH2:27][N:26]([CH2:29][C:30]3[CH:35]=[CH:34][C:33]([Cl:36])=[C:32]([CH3:37])[CH:31]=3)[CH2:25][CH2:24]2)=[O:16])[CH:3]=1
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참가 물질

6

반응물 4

HCID 887MethanolHCID 6228DimethylformamideHCID 8471TriethylamineHCID 667350421-[1-(4-Chloro-3-methyl-benzyl)-piperidin-4-yl]-5-oxo-pyrrolidine-2-carboxylic acid [3-bromo-5-(1-methyl-1H-tetrazol-5-yl)-phenyl]-amide

생성물 1

HCID 667331223-({1-[1-(4-Chloro-3-methyl-benzyl)-piperidin-4-yl]-5-oxo-pyrrolidine-2-carbonyl}-amino)-5-(1-methyl-1H-tetrazol-5-yl)-benzoic acid methyl ester

시약·촉매·용매 1

HCID 44119782Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매

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온도
80 °C

실험 절차

To a solution of 1-[1-(4-Chloro-3-methyl-benzyl)-piperidin-4-yl]-5-oxo-pyrrolidine-2-carboxylic acid [3-bromo-5-(1-methyl-1H-tetrazol-5-yl)-phenyl]-amide (400 mg) in MeOH (20 ml) was added triethylamine (140 μl), DMF (5 ml), and [1,1′-bis(diphenylphosphino)-ferrocen]palladium(II) chloride (50 mg) and the reaction stirred for 2 d at 80° C. under a 3 bar CO atmosphere. The reaction mixture was filtered and the filtrate concentrated in vacuum. The residue was partitioned between water and EtOAc and the organic layer was then separated, dried and concentrated in vacuum. The residue was purified by flash chromatography (DCM:MeOH 100:0 to 95:5 gradient) to give the title compound (400 mg). Rf=0.37 (95:5 DCM:MeOH).

후처리

  1. filtrationThe reaction mixture was filtered
  2. concentrationthe filtrate concentrated in vacuum
  3. customThe residue was partitioned between water and EtOAc
  4. customthe organic layer was then separated
  5. customdried
  6. concentrationconcentrated in vacuum
  7. customThe residue was purified by flash chromatography (DCM:MeOH 100:0 to 95:5 gradient)

출처 및 근거

ORD 기록
ord-1f11bb7d4a6249af86c4fb114c5f7d5c
출처 데이터셋
uspto-grants-2012_10
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08278302B2

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