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 2059644Notes

Reaction equation

HRID 2059644 reaction equation
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

Participants

6

Reactant 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

Product 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

Reagents, catalysts & solvents 1

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst

Conditions

Temperature
80 °C

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-1f11bb7d4a6249af86c4fb114c5f7d5c
Source dataset
uspto-grants-2012_10
Patent number
US08278302B2

Reaction notes

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