L-Proline → 1-{[3-(2-{3-cyano-4-[(1-methylethyl)oxy]phenyl}-1,3-thiazol-5-yl)-2-ethylphenyl]methyl}-L-proline

HRID 1942759Notes

Reaction equation

HRID 1942759 reaction equation
[CH2:1]([C:3]1[C:8]([CH:9]=O)=[CH:7][CH:6]=[CH:5][C:4]=1[C:11]1[S:15][C:14]([C:16]2[CH:17]=[CH:18][C:19]([O:24][CH:25]([CH3:27])[CH3:26])=[C:20]([CH:23]=2)[C:21]#[N:22])=[N:13][CH:12]=1)[CH3:2].[NH:28]1[CH2:35][CH2:34][CH2:33][C@H:29]1[C:30]([OH:32])=[O:31].C([BH3-])#N.[Na+]>C(O)C>[C:21]([C:20]1[CH:23]=[C:16]([C:14]2[S:15][C:11]([C:4]3[C:3]([CH2:1][CH3:2])=[C:8]([CH2:9][N:28]4[CH2:35][CH2:34][CH2:33][C@H:29]4[C:30]([OH:32])=[O:31])[CH:7]=[CH:6][CH:5]=3)=[CH:12][N:13]=2)[CH:17]=[CH:18][C:19]=1[O:24][CH:25]([CH3:27])[CH3:26])#[N:22]

Participants

5

Reactant 3

HCID 145742L-ProlineHCID 5003444Sodium cyanoborohydrideHCID 866590075-[5-(2-Ethyl-3-formylphenyl)-1,3-thiazol-2-yl]-2-[(1-methylethyl)oxy]benzonitrile

Product 1

HCID 545786961-{[3-(2-{3-cyano-4-[(1-methylethyl)oxy]phenyl}-1,3-thiazol-5-yl)-2-ethylphenyl]methyl}-L-prolineYield 25.8%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A solution of 5-[5-(2-ethyl-3-formylphenyl)-1,3-thiazol-2-yl]-2-[(1-methylethyl)oxy]benzonitrile (D73) (80 mg, 0.212 mmol) and L-proline (48.9 mg, 0.425 mmol) in Ethanol (10 mL) was stirred at room temperature for 15 min, then sodium cyanoborohydride (40.1 mg, 0.637 mmol) was added. The mixture was stirred at room temperature for 2 h. After concentration, the residue was partitioned between ethyl acetate and aqueous diluted HCl, washed with saturated brine. The organic phase was evaporated in vacuo. The residue was purified by mass Directed AutoPrep to afford 1-{[3-(2-{3-cyano-4-[(1-methylethyl)oxy]phenyl}-1,3-thiazol-5-yl)-2-ethylphenyl]methyl}-L-proline (E81) (26 mg) as a TFA salt.

Workup

  1. concentrationAfter concentration
  2. customthe residue was partitioned between ethyl acetate and aqueous diluted HCl
  3. washwashed with saturated brine
  4. customThe organic phase was evaporated in vacuo
  5. customThe residue was purified by mass

Sources & evidence

ORD record
ord-639d94a591054636b67a2f7d82ac83d7
Source dataset
uspto-grants-2013_03
Patent number
US08389508B2

Reaction notes

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