4-(Tetramethyl-1,3,2-dioxaborolan-2-yl)aniline → (1R,2R)-2-{4'-[(2-phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-biphenyl-4-carbonyl}-cyclopentanecarboxylic acid

HRID 557774Notes

Reaction equation

HRID 557774 reaction equation
Cl[C:2]1[CH:3]=[C:4]([CH:15]=[CH:16][C:17]=1[C:18]1[CH:23]=[CH:22][C:21]([NH:24][C:25]([C:27]2[N:28]=[C:29]([C:36]3[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=3)[O:30][C:31]=2[C:32]([F:35])([F:34])[F:33])=[O:26])=[CH:20]N=1)[C:5](N[C@@H](C(C)C)C(O)=O)=[O:6].C1(C2OC(C(F)(F)F)=C(C(NC3C=CC(C4C=CC(NC([C@@H:71]5[CH2:75][CH2:74][CH2:73][C@H:72]5[C:76]([OH:78])=[O:77])=O)=CC=4)=CC=3)=O)N=2)C=CC=CC=1.I[C:84]1C=CC(NC(C2N=C(C3C=CC=CC=3)OC=2C(F)(F)F)=O)=CC=1.CC1(C)C(C)(C)OB(C2C=CC(N)=CC=2)O1.C(OC(C1CCCC1C(O)=O)=O)C1C=CC=CC=1>>[C:36]1([C:29]2[O:30][C:31]([C:32]([F:33])([F:35])[F:34])=[C:27]([C:25]([NH:24][C:21]3[CH:20]=[CH:84][C:18]([C:17]4[CH:2]=[CH:3][C:4]([C:5]([C@@H:71]5[CH2:75][CH2:74][CH2:73][C@H:72]5[C:76]([OH:78])=[O:77])=[O:6])=[CH:15][CH:16]=4)=[CH:23][CH:22]=3)=[O:26])[N:28]=2)[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=1

Participants

6

Reactant 5

HCID 27346204-(Tetramethyl-1,3,2-dioxaborolan-2-yl)anilineHCID 25117944HCID 25117944, compoundHCID 57651950HCID 57651950, compoundHCID 57651972HCID 57651972, compoundHCID 66738491HCID 66738491, compound

Product 1

HCID 57651904(1R,2R)-2-{4'-[(2-phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-biphenyl-4-carbonyl}-cyclopentanecarboxylic acid

Procedure

With a method similar to that used for the preparation of (S)-2-(3-chloro-4-{5-[(2-phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-pyridin-2-yl}-benzoylamino)-3-methyl-butyric acid above, racemic trans-2-{4′-[(2-phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-biphenyl-4-ylcarbamoyl}-cyclopentanecarboxylic acid was prepared from 2-phenyl-5-trifluoromethyl-oxazole-4-carboxylic acid (4-iodo-phenyl)-amide, 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline and cyclopentane-1,2-dicarboxylic acid monobenzyl ester. The benzyl ester was then removed by hydrogenolysis. The racemic mixture was separated by chiral SFC to afford (1R,2R)-2-{4′-[(2-phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-biphenyl-4-carbonyl}-cyclopentanecarboxylic acid (or enantiomer). LCMS calcd for C30H24F3N3O5 (m/e) 563, obsd 564 (M+H).

Workup

  1. customThe benzyl ester was then removed by hydrogenolysis
  2. customThe racemic mixture was separated by chiral SFC

Sources & evidence

ORD record
ord-0104f5ec996b4d41a77edbb0b2e7348c
Source dataset
uspto-grants-2011_11
Patent number
US08058299B2

Reaction notes

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