Sodium Carbonate → 3-(Biphenyl-4-yl)-(2S)-[(3'-chloro-4'-fluoro-4-hydroxy-biphenyl-3-carbonyl)-amino]-propionic Acid Methyl Ester

HRID 1245067Notes

Reaction equation

HRID 1245067 reaction equation
[CH3:1][O:2][C:3](=[O:29])[C@@H:4]([NH:18][C:19](=[O:28])[C:20]1[CH:25]=[C:24](Br)[C:23](O)=[CH:22][CH:21]=1)[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[CH:8][CH:7]=1.[Cl:30][C:31]1[CH:32]=[C:33](B(O)O)[CH:34]=[CH:35][C:36]=1[F:37].C([O-])([O-])=[O:42].[Na+].[Na+]>COCCOC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:1][O:2][C:3](=[O:29])[C@@H:4]([NH:18][C:19]([C:20]1[CH:21]=[C:22]([C:33]2[CH:34]=[CH:35][C:36]([F:37])=[C:31]([Cl:30])[CH:32]=2)[CH:23]=[CH:24][C:25]=1[OH:42])=[O:28])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[CH:8][CH:7]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 27346603-Chloro-4-fluorophenylboronic Acid (contains varying amounts of Anhydride)HCID 692051283-(biphenyl-4-yl)-(2S)-(5-bromo-4-hydroxy-benzoylamino)-propionic acid methyl ester

Product 1

HCID 113865603-(Biphenyl-4-yl)-(2S)-[(3'-chloro-4'-fluoro-4-hydroxy-biphenyl-3-carbonyl)-amino]-propionic Acid Methyl EsterYield 70%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

To 0.05 g (0.1 mmol) of above resin-bound 3-(biphenyl-4-yl)-(2S)-(5-bromo-4-hydroxy-benzoylamino)-propionic acid methyl ester in 2.0 mL of DME were added 52.0 mg (0.3 mmol) of 3-chloro-4-fluorophenylboronic acid, 30 mg (0.03 mmol) of Pd(PPh3)4, and 0.3 mL (0.6 mmol) of 2N Na2CO3 solution. The mixture was heated to 80° C. for 12 h. The resin was washed with H2O, DMF, MeOH, DCM three times of each and cleaved with TMSBr/TFA/DCM (1:1:5) at rt for 4 h. The residue obtained after removing the solvent was purified by chromatography (DCM) to give 35 mg (70%) of title compound LC/MS (m/z): 490 (M+1)+.

Workup

  1. washThe resin was washed with H2O, DMF, MeOH, DCM three times of each and
  2. customThe residue obtained
  3. customafter removing the solvent
  4. customwas purified by chromatography (DCM)

Sources & evidence

ORD record
ord-618671e654984eb6aff1410076b88f1c
Source dataset
uspto-grants-2006_10
Patent number
US07122580B2

Reaction notes

Loading…