Acetic Acid → 1-[2-(3-{5-[3-cyano-4-(2-methylpropyl)phenyl]-1,3,4-thiadiazol-2-yl}-2-ethylphenyl)ethyl]-L-proline

HRID 1942753Notes

Reaction equation

HRID 1942753 reaction equation
[CH2:1]([C:3]1[C:8]([CH2:9][CH:10]=O)=[CH:7][CH:6]=[CH:5][C:4]=1[C:12]1[S:16][C:15]([C:17]2[CH:18]=[CH:19][C:20]([CH2:25][CH:26]([CH3:28])[CH3:27])=[C:21]([CH:24]=2)[C:22]#[N:23])=[N:14][N:13]=1)[CH3:2].[NH:29]1[CH2:36][CH2:35][CH2:34][C@H:30]1[C:31]([OH:33])=[O:32].CC(O)=O.C([BH3-])#N.[Na+]>C(O)C>[C:22]([C:21]1[CH:24]=[C:17]([C:15]2[S:16][C:12]([C:4]3[C:3]([CH2:1][CH3:2])=[C:8]([CH2:9][CH2:10][N:29]4[CH2:36][CH2:35][CH2:34][C@H:30]4[C:31]([OH:33])=[O:32])[CH:7]=[CH:6][CH:5]=3)=[N:13][N:14]=2)[CH:18]=[CH:19][C:20]=1[CH2:25][CH:26]([CH3:28])[CH3:27])#[N:23]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 145742L-ProlineHCID 5003444Sodium cyanoborohydrideHCID 86659001HCID 86659001, compound

Product 1

HCID 545778101-[2-(3-{5-[3-cyano-4-(2-methylpropyl)phenyl]-1,3,4-thiadiazol-2-yl}-2-ethylphenyl)ethyl]-L-prolineYield 41.9%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of 5-{5-[2-ethyl-3-(2-oxoethyl)phenyl]-1,3,4-thiadiazol-2-yl}-2-(2-methylpropyl)benzonitrile (D31) (99 mg, 0.254 mmol) in Ethanol (15 mL) stirred at room temperature was added L-proline (117 mg, 1.017 mmol) and AcOH (0.15 mL, 2.62 mmol). The reaction mixture was stirred at room temperature for 10 min, and sodium cyanoborohydride (31.9 mg, 0.508 mmol) was added. The reaction mixture was continuously stirred overnight. The reaction was quenched with water and DCM was evaporated in vacuo. The mixture was extracted by EA/THF for 3 times. The combined organic solution was washed with brine, concentrated and purified by Mass Directed AutoPrep to afford 1-[2-(3-{5-[3-cyano-4-(2-methylpropyl)phenyl]-1,3,4-thiadiazol-2-yl}-2-ethylphenyl)ethyl]-L-proline (E59) (52 mg) as a off-white solid.

Workup

  1. waitThe reaction mixture was continuously stirred overnight
  2. customThe reaction was quenched with water and DCM
  3. customwas evaporated in vacuo
  4. extractionThe mixture was extracted by EA/THF for 3 times
  5. washThe combined organic solution was washed with brine
  6. concentrationconcentrated
  7. custompurified by Mass Directed AutoPrep

Sources & evidence

ORD record
ord-b8a60c96af524457a4baa300f4f165c3
Source dataset
uspto-grants-2013_03
Patent number
US08389508B2

Reaction notes

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