HCID 59547338, compound → HCID 59547307, compound

HRID 2038580Notes

Reaction equation

HRID 2038580 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([N:8]2[C:37](=[O:38])[CH2:36][C@@:10]3([CH2:14][N:13]([C:15](=[O:31])[C@@H:16]([NH:21][C:22](=[O:30])[CH2:23][CH:24]4[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]4)[C:17]([CH3:20])([CH3:19])[CH3:18])[C@H:12]([C:32]([O:34]C)=[O:33])[CH2:11]3)[CH2:9]2)[CH:5]=[CH:6][CH:7]=1>C(#N)C.O>[Cl:1][C:2]1[CH:3]=[C:4]([N:8]2[C:37](=[O:38])[CH2:36][C@@:10]3([CH2:14][N:13]([C:15](=[O:31])[C@@H:16]([NH:21][C:22](=[O:30])[CH2:23][CH:24]4[CH2:25][CH2:26][CH2:27][CH2:28][CH2:29]4)[C:17]([CH3:20])([CH3:18])[CH3:19])[C@H:12]([C:32]([OH:34])=[O:33])[CH2:11]3)[CH2:9]2)[CH:5]=[CH:6][CH:7]=1

Participants

3

Reactant 1

HCID 59547338HCID 59547338, compound

Product 1

HCID 59547307HCID 59547307, compoundYield 100,000%

Reagents, catalysts & solvents 1

HCID 18373917Acetonitrile--water (1/1)Solvent

Procedure

The methyl ester (3S,5R)-methyl-7-(3-chlorophenyl)-2-((S)-2-(2-cyclohexylacetamido)-3,3-dimethyl butanoyl)-8-oxo-2,7-diazaspiro[4.4]nonane-3-carboxylate (E7a) (12.8 mg, 23 μmol) was taken up in THF (1.0 ml) and MeOH (50 μl) was added. To this was added 1N LiOH in water (46 μl, 2.0 eq). The reaction was stirred at room temperature overnight and quenched at 0° C. with 1N HCl in water (46 μl, 2.0 eq). The reaction was concentrated to dryness to give (3S,5R)-7-(3-chlorophenyl)-2-((S)-2-(2-cyclohexylacetamido)-3,3-dimethylbutanoyl)-8-oxo-2,7-diazaspiro[4.4]nonane-3-carboxylic acid (F7a) (23 μmol). LCMS for C28H38N3O5Cl 531.25 [M], found ES+ 532.3 [M+H]+ and ES− 530.5 [M−H]− at 3.2 minutes retention time, using 10-90% acetonitrile/water (with 0.1% formic acid buffer) gradient over 5 minutes. The minor diastereomer (3S,5S)-methyl 7-(3-chlorophenyl)-2-((S)-2-(2-cyclohexylacetamido)-3,3-dimethylbutanoyl)-8-oxo-2,7-diazaspiro[4.4]nonane-3-carboxylate (E7b) (6.6 mg, 12 μmol) was treated similarly to give (3S,5S)-7-(3-chlorophenyl)-2-((S)-2-(2-cyclohexylacetamido)-3,3-dimethylbutanoyl)-8-oxo-2,7-diazaspiro[4.4]nonane-3-carboxylic acid (F7b) (12 mmol). LCMS for C28H38N3O5Cl 531.25 [M], found ES+ 532.25 [M+H]+ and ES− 530.25 [M−H] at 3.3 minutes retention time, using 10-90% acetonitrile/water (with 0.1% formic acid buffer) gradient over 5 minutes.

Workup

  1. custom530.5 [M−H]− at 3.2 minutes retention time
  2. customover 5 minutes

Sources & evidence

ORD record
ord-4cc54171245c467b92ab35c2d049591e
Source dataset
uspto-grants-2013_11
Patent number
US08575208B2

Reaction notes

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