Potassium Carbonate → (S)-methyl 2-((4-(5-(3-cyano-4-isopropoxyphenyl)-1,3,4-thiadiazol-2-yl)-2,3-dihydro-1H-inden-1-yl)amino)acetate

HRID 1891470Notes

Reaction equation

HRID 1891470 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.C([O-])([O-])=O.[K+].[K+].Br[CH2:36][C:37]([O:39][CH3:40])=[O:38]>CC#N>[C:22]([C:21]1[CH:24]=[C:17]([C:15]2[S:16][C:12]([C:7]3[CH:8]=[CH:9][CH:10]=[C:11]4[C:6]=3[CH2:5][CH2:4][C@@H:3]4[NH:2][CH2:36][C:37]([O:39][CH3:40])=[O:38])=[N:13][N:14]=2)[CH:18]=[CH:19][C:20]=1[O:25][CH:26]([CH3:28])[CH3:27])#[N:23]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 60984Methyl bromoacetate2×HCID 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 58367384(S)-methyl 2-((4-(5-(3-cyano-4-isopropoxyphenyl)-1,3,4-thiadiazol-2-yl)-2,3-dihydro-1H-inden-1-yl)amino)acetateYield 90.4%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

Prepared using General Procedure 9. To a suspension of (S)-5-(5-(1-amino-2,3-dihydro-1H-inden-4-yl)-1,3,4-thiadiazol-2-yl)-2-isopropoxybenzonitrile hydrochloride 4 (150 mg, 0.36 mmol) in CH3CN (5 mL) was added K2CO3 (150.9 mg, 1.09 mmol) and methyl 2-bromoacetate (67 mg, 0.43 mmol). The suspension was stirred at 80° C. After 6 h more methyl 2-bromoacetate (6.7 mg, 0.043 mmol) was added and heating continued for 12 h. The reaction mixture was filtered and concentrated. The residue was re-suspended in EA (15 mL), washed with water and brine, dried and concentrated. The product was purified by a silica gel column chromatography (MeOH/DCM) to afford 146 mg (90%) of (S)-methyl 2-((4-(5-(3-cyano-4-isopropoxyphenyl)-1,3,4-thiadiazol-2-yl)-2,3-dihydro-1H-inden-1-yl)amino)acetate as white solid. LCMS-ESI (m/z) calculated for C24H24N4O3S: 448.2; found 449.1 [M+H]+, tR=2.48 min.

Workup

  1. customPrepared
  2. temperatureheating
  3. filtrationThe reaction mixture was filtered
  4. concentrationconcentrated
  5. washwashed with water and brine
  6. customdried
  7. concentrationconcentrated
  8. customThe product was purified by a silica gel column chromatography (MeOH/DCM)

Sources & evidence

ORD record
ord-58cedeec23164d59a5f2e9fcff99e87d
Source dataset
uspto-grants-2013_08
Patent number
US08507538B2

Reaction notes

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