1,2-Dichloroethane → 1,1-Dimethylethyl (3R)-3-(cyclopentyl methyl)-4-oxo-4-{(5S)-5-[(2-pyridinylamino)carbonyl]-4,5-dihydro-1H-pyrazol-1-yl}butanoate

HRID 1396998Notes

Reaction equation

HRID 1396998 reaction equation
[CH:1]1([CH2:6][C@H:7]([CH2:18][C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[C:8]([N:10]2[C@H:14]([C:15](O)=[O:16])[CH2:13][CH:12]=[N:11]2)=[O:9])[CH2:5][CH2:4][CH2:3][CH2:2]1.[N:26]1[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=1[NH2:32].CCN(C(C)C)C(C)C.N1C2C(=NC=CC=2)N(O)N=1.C(Cl)CCl>ClCCl>[CH:1]1([CH2:6][C@@H:7]([C:8](=[O:9])[N:10]2[C@H:14]([C:15]([NH:32][C:27]3[CH:28]=[CH:29][CH:30]=[CH:31][N:26]=3)=[O:16])[CH2:13][CH:12]=[N:11]2)[CH2:18][C:19]([O:21][C:22]([CH3:24])([CH3:25])[CH3:23])=[O:20])[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 104392-AminopyridineHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 86706409HCID 86706409, compound

Product 1

HCID 867064101,1-Dimethylethyl (3R)-3-(cyclopentyl methyl)-4-oxo-4-{(5S)-5-[(2-pyridinylamino)carbonyl]-4,5-dihydro-1H-pyrazol-1-yl}butanoate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a 1000 ml round bottom flask under N2 was added (5S)-1-{(2R)-2-(cyclopentylmethyl)-4-[(1,1-dimethylethyl)oxy]-4-oxobutanoyl}-4,5-dihydro-1H-pyrazole-5-carboxylic acid (27.7 g, 79 mmol) in dichloromethane (DCM) (700 mL) at 0° C., followed by 2-pyridinamine (14.79 g, 157 mmol), DIPEA (68.6 mL, 393 mmol), 3H-[1,2,3]triazolo[4,5-b]pyridin-3-ol (21.40 g, 157 mmol) and EDC (30.1 g, 157 mmol). The mixture was allowed to warm up to room temperature and stirring continued overnight. LCMS showed that the desired product was ˜56%. After another 24 h, LCMS indicated no starting material left. The organic solution was washed with water (300 mL), 10% citric acid (2×300 mL) and brine, dried (Na2SO4), filtered, and concentrated to afford 1,1-dimethylethyl (3R)-3-(cyclopentylmethyl)-4-oxo-4-{(5S)-5-[(2-pyridinylamino)carbonyl]-4,5-dihydro-1H-pyrazol-1-yl}butanoate (29.1 g, 58.4 mmol, 74% yield) as a brown gummy solid. LCMS: [M+H]+: 429.2.

Sources & evidence

ORD record
ord-35b3d1db4bad49fea2e8dba08c9db77a
Source dataset
uspto-grants-2014_12
Patent number
US08901119B2

Reaction notes

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