HCID 86605162, compound → HCID 59767796, compound

HRID 2217286Notes

Reaction equation

HRID 2217286 reaction equation
[C:1]([C:3]1([NH:6][C:7](=[O:38])[C@H:8]([CH2:33][C:34]([F:37])([CH3:36])[CH3:35])[NH:9][C@@H:10]([C:15]2[CH:20]=[CH:19][C:18]([C:21]3[CH:26]=[CH:25][C:24]([C:27]([OH:32])([CH3:31])[CH:28]([F:30])[F:29])=[CH:23][CH:22]=3)=[CH:17][CH:16]=2)[C:11]([F:14])([F:13])[F:12])[CH2:5][CH2:4]1)#[N:2]>C(O)C>[C:1]([C:3]1([NH:6][C:7](=[O:38])[C@H:8]([CH2:33][C:34]([F:37])([CH3:35])[CH3:36])[NH:9][C@@H:10]([C:15]2[CH:20]=[CH:19][C:18]([C:21]3[CH:26]=[CH:25][C:24]([C@:27]([OH:32])([CH3:31])[CH:28]([F:30])[F:29])=[CH:23][CH:22]=3)=[CH:17][CH:16]=2)[C:11]([F:14])([F:13])[F:12])[CH2:5][CH2:4]1)#[N:2]

Participants

3

Reactant 1

HCID 86605162HCID 86605162, compound

Product 1

HCID 59767796HCID 59767796, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

The 1:1 diastereomeric mixture from step 2 in example 9 (80 mg) was dissolved in ethanol (2 mL). The mixture of compounds was resolved in ˜10 injections (10×200 μL) with a Chiralcel OD semi-preparative column (2 cm I.D.×25 cm) eluting with 32.5% 2-propanol in hexanes and a flow rate of 6 mL/min. The fast fractions eluted at 21-23 min were pooled and concentrated to give N1-(1-cyanocyclopropyl)-N2-((1S)-1-{4′-[(1R)-2,2-difluoro-1-hydroxy-1-methylethyl]biphenyl-4-yl}-2,2,2-trifluoroethyl)-4-fluoro-L-leucinamide as a white powder (98% d.e.). Stereochemistry is tentative.

Workup

  1. additionThe mixture of compounds
  2. washeluting with 32.5% 2-propanol in hexanes
  3. washThe fast fractions eluted at 21-23 min
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-7c5e5a1ce6cc4a5cb27adaf53bc11d7d
Source dataset
uspto-grants-2008_08
Patent number
US07407959B2

Reaction notes

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