2-Propanol, sodium salt (1:1) → (S)-tert-butyl (4-(5-(3-cyano-4-isopropoxyphenyl)-1,3,4-thiadiazol-2-yl)-2,3-dihydro-1H-inden-1-yl)carbamate

HRID 1891462Notes

Reaction equation

HRID 1891462 reaction equation
[C:1]([O:5][C:6](=[O:31])[NH:7][C@@H:8]1[C:16]2[C:11](=[C:12]([C:17]3[S:18][C:19]([C:22]4[CH:27]=[CH:26][C:25](F)=[C:24]([C:29]#[N:30])[CH:23]=4)=[N:20][N:21]=3)[CH:13]=[CH:14][CH:15]=2)[CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[CH3:32][CH:33]([CH3:35])[O-:34].[Na+]>CC(O)C>[C:1]([O:5][C:6](=[O:31])[NH:7][C@@H:8]1[C:16]2[C:11](=[C:12]([C:17]3[S:18][C:19]([C:22]4[CH:27]=[CH:26][C:25]([O:34][CH:33]([CH3:35])[CH3:32])=[C:24]([C:29]#[N:30])[CH:23]=4)=[N:20][N:21]=3)[CH:13]=[CH:14][CH:15]=2)[CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 109204432-Propanol, sodium salt (1:1)HCID 58367252(S)-tert-butyl (4-(5-(3-cyano-4-fluorophenyl)-1,3,4-thiadiazol-2-yl)-2,3-dihydro-1H-inden-1-yl)carbamate

Product 1

HCID 58367217(S)-tert-butyl (4-(5-(3-cyano-4-isopropoxyphenyl)-1,3,4-thiadiazol-2-yl)-2,3-dihydro-1H-inden-1-yl)carbamateYield 42%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
60 °C

Procedure

Prepared using General Procedure 2. To a solution of (S)-tert-butyl(4-(5-(3-cyano-4-fluorophenyl)-1,3,4-thiadiazol-2-yl)-2,3-dihydro-1H-inden-1-yl)carbamate (2.5 g 5.7 mmol) in IPA (30 mL) was added sodium isopropoxide (0.61 g, 7.4 mmol). The reaction mixture was heated at 60° C. for 4 h. Upon cooling, the mixture was concentrated to 50% volume and the suspension was cooled to 0° C. The resulting solid was filtered and dried under high vacuum to afford 1.14 g (42%) of (S)-tert-butyl(4-(5-(3-cyano-4-isopropoxyphenyl)-1,3,4-thiadiazol-2-yl)-2,3-dihydro-1H-inden-1-yl)carbamate as off-white solid. LCMS-ESI (m/z) calculated for C26H28N4O3S: 476.2; found 477.2 (M+H). tR=4.12 min. 1H NMR (400 MHz, CDCl3) δ 8.26-8.04 (m, 2H), 7.82 (d, J=7.7 Hz, 1H), 7.49 (d, J=7.5 Hz, 1H), 7.38 (d, J=7.6 Hz, 1H), 7.09 (d, J=9.0 Hz, 1H), 5.38-5.08 (m, 1H), 4.94-4.62 (m, 1H), 3.54-3.32 (m, 1H), 3.21 (s, 1H), 2.80-2.59 (m, 1H), 1.97-1.74 (m, 1H), 1.52-1.35 (m, 15H). 13C NMR (101 MHz, CDCl3) δ 166.93, 165.54, 161.59, 155.65, 145.84, 142.05, 133.28, 128.71, 127.59, 126.64, 126.33, 122.72, 115.54, 113.86, 103.69, 79.59, 72.50, 60.35, 55.73, 33.78, 31.27, 28.39, 21.74.

Workup

  1. customPrepared
  2. temperatureUpon cooling
  3. concentrationthe mixture was concentrated to 50% volume
  4. temperaturethe suspension was cooled to 0° C
  5. filtrationThe resulting solid was filtered
  6. customdried under high vacuum

Sources & evidence

ORD record
ord-3916a2faec1a4138928483b0fcbf0275
Source dataset
uspto-grants-2013_08
Patent number
US08507538B2

Reaction notes

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