Diisopropylethylamine → 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

HRID 2059643Notes

Reaction equation

HRID 2059643 reaction equation
[Cl:1][C:2]1[CH:23]=[CH:22][C:5]([CH2:6][N:7]2[CH2:12][CH2:11][CH:10]([N:13]3[C:17](=[O:18])[CH2:16][CH2:15][CH:14]3[C:19]([OH:21])=O)[CH2:9][CH2:8]2)=[CH:4][C:3]=1[CH3:24].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[Br:58][C:59]1[CH:60]=[C:61]([NH2:71])[CH:62]=[C:63]([C:65]2[N:69]([CH3:70])[N:68]=[N:67][N:66]=2)[CH:64]=1>CN(C=O)C>[Br:58][C:59]1[CH:60]=[C:61]([NH:71][C:19]([CH:14]2[CH2:15][CH2:16][C:17](=[O:18])[N:13]2[CH:10]2[CH2:11][CH2:12][N:7]([CH2:6][C:5]3[CH:22]=[CH:23][C:2]([Cl:1])=[C:3]([CH3:24])[CH:4]=3)[CH2:8][CH2:9]2)=[O:21])[CH:62]=[C:63]([C:65]2[N:69]([CH3:70])[N:68]=[N:67][N:66]=2)[CH:64]=1

Participants

6

Reactant 4

HCID 81531Diisopropylethylamine2×HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 667333043-Bromo-5-(1-methyl-1H-tetrazol-5-yl)-phenylamineHCID 667333601-[1-(4-Chloro-3-methyl-benzyl)-piperidin-4-yl]-5-oxo-pyrrolidine-2-carboxylic acid

Product 1

HCID 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

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-[1-(4-Chloro-3-methyl-benzyl)-piperidin-4-yl]-5-oxo-pyrrolidine-2-carboxylic acid as DIPEA salt (2.6 g) in DMF (100 ml) was added DIPEA (2.1 g), and HATU (4 g). 3-Bromo-5-(1-methyl-1H-tetrazol-5-yl)-phenylamine (1.4 g) was added and the reaction stirred overnight at rt. The reaction mixture was filtered and the filtrate partitioned between water and EtOAc. The organic layer was separated, dried and concentrated in vacuum and the residue purified by flash chromatography (DCM:MeOH 100:0 to 95:5 gradient) to give the title compound (400 mg). Rf=0.19 (95:5 DCM:MeOH).

Workup

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

Sources & evidence

ORD record
ord-caddde574d7a48cd9cac72b879b95b9f
Source dataset
uspto-grants-2012_10
Patent number
US08278302B2

Reaction notes

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