Triphenylphosphine → (S)-1-[3-(2-{[4-chloro-3-(4-cyano-6-trifluoromethyl-pyridin-3-yl)-benzoyl]-methyl-amino}-phenoxy)-propyl]-pyrrolidine-2-carboxylic acid

HRID 448954Notes

Reaction equation

HRID 448954 reaction equation
[Cl:1][C:2]1[CH:18]=[CH:17][C:5]([C:6]([N:8]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[OH:16])[CH3:9])=[O:7])=[CH:4][C:3]=1[C:19]1[CH:20]=[N:21][C:22]([C:27]([F:30])([F:29])[F:28])=[CH:23][C:24]=1[C:25]#[N:26].C([O:35][C:36]([C@@H:38]1[CH2:42][CH2:41][CH2:40][N:39]1[CH2:43][CH2:44][CH2:45]O)=[O:37])(C)(C)C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>C1COCC1>[Cl:1][C:2]1[CH:18]=[CH:17][C:5]([C:6]([N:8]([CH3:9])[C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[O:16][CH2:45][CH2:44][CH2:43][N:39]2[CH2:40][CH2:41][CH2:42][C@H:38]2[C:36]([OH:37])=[O:35])=[O:7])=[CH:4][C:3]=1[C:19]1[CH:20]=[N:21][C:22]([C:27]([F:30])([F:28])[F:29])=[CH:23][C:24]=1[C:25]#[N:26]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 68602721(S)-1-(3-hydroxy-propyl)-pyrrolidine-2-carboxylic acid tert-butyl esterHCID 686028394-chloro-3-(4-cyano-6-trifluoromethyl-pyridin-3-yl)-N-(2-hydroxy-phenyl)-N-methyl-benzamide

Product 1

HCID 59370365(S)-1-[3-(2-{[4-chloro-3-(4-cyano-6-trifluoromethyl-pyridin-3-yl)-benzoyl]-methyl-amino}-phenoxy)-propyl]-pyrrolidine-2-carboxylic acid

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To 4-chloro-3-(4-cyano-6-trifluoromethyl-pyridin-3-yl)-N-(2-hydroxy-phenyl)-N-methyl-benzamide (30 mg, 0.069 mmol) dissolved in THF (700 μL), (S)-1-(3-hydroxy-propyl)-pyrrolidine-2-carboxylic acid tert-butyl ester (18 mg, 0.078 mmol), triphenylphosphine (26 mg, 0.1 mmol) and DIAD (20 μL, 0.1 mmol) were added. The mixture was stirred at rt overnight, concentrated, diluted with 1 mL MeOH and purified by prep HPLC. The resulting (S)-1-[3-(2-{[4-chloro-3-(4-cyano-6-trifluoromethyl-pyridin-3-yl)-benzoyl]-methyl-amino}-phenoxy)-propyl]-pyrrolidine-2-carboxylic acid tert-butyl ester was treated with 50% TFA in DCM (2 mL), stirred at rt for 4 hrs and concentrated yielding (5)-1-[3-(2-{[4-chloro-3-(4-cyano-6-trifluoromethyl-pyridin-3-yl)-benzoyl]-methyl-amino}-phenoxy)-propyl]-pyrrolidine-2-carboxylic acid 50-1. MS: 587.4 (M+H)+, tR=4.34 min (method 3).

Workup

  1. concentrationconcentrated
  2. additiondiluted with 1 mL MeOH
  3. custompurified by prep HPLC
  4. additionThe resulting (S)-1-[3-(2-{[4-chloro-3-(4-cyano-6-trifluoromethyl-pyridin-3-yl)-benzoyl]-methyl-amino}-phenoxy)-propyl]-pyrrolidine-2-carboxylic acid tert-butyl ester was treated with 50% TFA in DCM (2 mL)
  5. stirringstirred at rt for 4 hrs
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-4e6f9d03cde24dec9ab22091dfe8ee3d
Source dataset
uspto-grants-2013_07
Patent number
US08481738B2

Reaction notes

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