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 1422395Notes

Reaction equation

HRID 1422395 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-c65f226b3cde472d967acdbdca94b259
Source dataset
uspto-grants-2015_01
Patent number
USRE045323E1

Reaction notes

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