1H-imidazole-2-carbaldehyde → (S)-5-(5-(1-(((1H-imidazol-2-yl)methyl)amino)-2,3-dihydro-1H-inden-4-yl)-1,3,4-thiadiazol-2-yl)-2-isopropoxybenzonitrile

HRID 1891475Notes

Reaction equation

HRID 1891475 reaction equation
Cl.[NH2:2][C@@H:3]1[C:11]2[C:6](=[C:7]([C:12]3[S:16][C:15]([C:17]4[CH:18]=[CH:19][C:20]([O:25][CH:26]([CH3:28])[CH3:27])=[C:21]([CH:24]=4)[C:22]#[N:23])=[N:14][N:13]=3)[CH:8]=[CH:9][CH:10]=2)[CH2:5][CH2:4]1.[NH:29]1[CH:33]=[CH:32][N:31]=[C:30]1[CH:34]=O.[BH4-].[Na+]>CO.C(O)(=O)C>[NH:29]1[CH:33]=[CH:32][N:31]=[C:30]1[CH2:34][NH:2][C@@H:3]1[C:11]2[C:6](=[C:7]([C:12]3[S:16][C:15]([C:17]4[CH:18]=[CH:19][C:20]([O:25][CH:26]([CH3:28])[CH3:27])=[C:21]([CH:24]=4)[C:22]#[N:23])=[N:14][N:13]=3)[CH:8]=[CH:9][CH:10]=2)[CH2:5][CH2:4]1

Participants

6

Reactant 3

HCID 249551H-imidazole-2-carbaldehydeHCID 4311764Sodium borohydrideHCID 67193845(S)-5-(5-(1-amino-2,3-dihydro-1H-inden-4-yl)-1,3,4-thiadiazol-2-yl)-2-isopropoxybenzonitrile hydrochloride

Product 1

HCID 53232432(S)-5-(5-(1-(((1H-imidazol-2-yl)methyl)amino)-2,3-dihydro-1H-inden-4-yl)-1,3,4-thiadiazol-2-yl)-2-isopropoxybenzonitrileYield 81%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 887MethanolSolvent

Conditions

Temperature
55 °C

Procedure

Prepared using General Procedure 11. To (S)-5-(5-(1-amino-2,3-dihydro-1H-inden-4-yl)-1,3,4-thiadiazol-2-yl)-2-isopropoxybenzonitrile hydrochloride 4 (25 mg, 0.06 mmol) and 1H-imidazole-2-carbaldehyde (6.4 mg, 0.06 mmol) in anhydrous MeOH (1 mL) was added acetic acid (1 drop). The solution was stirred at 55° C. for 3 h before cooling to room temperature and the addition of NaBH4 (4.6 mg, 0.12 mmol). The mixture was stirred at room temperature for 12 h. The reaction mixture was quenched with water (0.5 mL) and partitioned between EA (5 mL) and water (5 mL). The organic layers washed with water and brine, and the product purified by preparative HPLC to afford 22 mg (81%) of (S)-5-(5-(1-(((1H-imidazol-2-yl)methyl)amino)-2,3-dihydro-1H-inden-4-yl)-1,3,4-thiadiazol-2-yl)-2-isopropoxybenzonitrile 28 as half-white solid. LCMS-ESI (m/z) calculated for C25H24N6OS: 456.2; found 457.2 [M+H]+, tR=2.38 min.

Workup

  1. customPrepared
  2. temperaturebefore cooling to room temperature
  3. stirringThe mixture was stirred at room temperature for 12 h
  4. customThe reaction mixture was quenched with water (0.5 mL)
  5. custompartitioned between EA (5 mL) and water (5 mL)
  6. washThe organic layers washed with water and brine
  7. customthe product purified by preparative HPLC

Sources & evidence

ORD record
ord-1159e38ae56c486aae46351828009d80
Source dataset
uspto-grants-2013_08
Patent number
US08507538B2

Reaction notes

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