Methylamine → 3'-Chloro-4'-fluoro-4-hydroxy-biphenyl-3-carboxylic acid (2-biphenyl-4-yl-1(S)-methylcarbamoyl-ethyl)-amide

HRID 2373794Notes

Reaction equation

HRID 2373794 reaction equation
[C:1]1([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[CH:6]=[CH:5][C:4]([CH2:7][C@H:8]([NH:12][C:13]([C:15]2[CH:16]=[C:17]([C:22]3[CH:27]=[CH:26][C:25]([F:28])=[C:24]([Cl:29])[CH:23]=3)[CH:18]=[CH:19][C:20]=2[OH:21])=[O:14])[C:9]([OH:11])=O)=[CH:3][CH:2]=1.COC(=O)[C@@H:39]([NH:53]C(C1C=C(C2C=CC(F)=C(Cl)C=2)C=CC=1O)=O)CC1C=CC(C2C=CC=CC=2)=CC=1.CN.C1COCC1.C[Si](Br)(C)C.C(O)(C(F)(F)F)=O.C(Cl)Cl>>[C:1]1([C:30]2[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=2)[CH:2]=[CH:3][C:4]([CH2:7][C@H:8]([NH:12][C:13]([C:15]2[CH:16]=[C:17]([C:22]3[CH:27]=[CH:26][C:25]([F:28])=[C:24]([Cl:29])[CH:23]=3)[CH:18]=[CH:19][C:20]=2[OH:21])=[O:14])[C:9](=[O:11])[NH:53][CH3:39])=[CH:5][CH:6]=1

Participants

6

Reactant 5

HCID 6329MethylamineHCID 8028TetrahydrofuranHCID 113865603-(Biphenyl-4-yl)-(2S)-[(3'-chloro-4'-fluoro-4-hydroxy-biphenyl-3-carbonyl)-amino]-propionic Acid Methyl EsterHCID 587176513-(Biphenyl-4-yl)-(2S)-[(3'-chloro-4'-fluoro-4-hydroxy-biphenyl-3-carbonyl)-amino]-propionic acidHCID 86597135TMSBr TFA DCM

Product 1

HCID 598525953'-Chloro-4'-fluoro-4-hydroxy-biphenyl-3-carboxylic acid (2-biphenyl-4-yl-1(S)-methylcarbamoyl-ethyl)-amide

Procedure

Resin bound 3-(Biphenyl-4-yl)-(2S)-[(3′-chloro-4′-fluoro-4-hydroxy-biphenyl-3-carbonyl)-amino]-propionic acid (30 mg, 0.09 mmol) prepared from resin bound 3-(Biphenyl-4-yl)-(2S)-[(3′-chloro-4′-fluoro-4-hydroxy-biphenyl3-carbonyl)-amino]-propionic acid methyl ester following general procedure C, was reacted with methyl amine in THF(0.45 mmol) as described in general procedure A, then cleaved with TMSBr/TFA/DCM (1:1:5) at rt for 4 h. The residue obtained after removing the solvent was purified by chromatography to give the title compound. (36 mg). LC/MS (m/z): 503 (M+1)+.

Workup

  1. customThe residue obtained
  2. customafter removing the solvent
  3. customwas purified by chromatography

Sources & evidence

ORD record
ord-ad4486667faf474c95cc4dafd31bef55
Source dataset
uspto-grants-2008_12
Patent number
US07459472B2

Reaction notes

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