Hydrochloric Acid → HCID 67196983, compound

HRID 1891464Notes

Reaction equation

HRID 1891464 reaction equation
C(OC(=O)[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:28][CH:29]([CH3:31])[CH3:30])=[C:24]([C:32]#[N:33])[CH:23]=4)=[CH:20][N:21]=3)[CH:13]=[CH:14][CH:15]=2)[CH2:10][CH2:9]1)(C)(C)C.[ClH:35]>O1CCOCC1.C(OCC)C>[ClH:35].[NH2:7][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:28][CH:29]([CH3:31])[CH3:30])=[C:24]([CH:23]=4)[C:32]#[N:33])=[CH:20][N:21]=3)[CH:13]=[CH:14][CH:15]=2)[CH2:10][CH2:9]1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 86710465HCID 86710465, compound

Product 1

HCID 67196983HCID 67196983, compoundYield 100%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
55 °C

Procedure

Prepared using General Procedure 5. To a stirred solution of (S)-tert-butyl(4-(5-(3-cyano-4-isopropoxyphenyl)thiazol-2-yl)-2,3-dihydro-1H-inden-1-yl)carbamate (1.0 g, 2.1 mmol) in 1,4-dioxane (5 mL) was added 4N HCl solution in 1,4-dioxane (5 mL). The reaction mixture was stirred at 55° C. for 2.5 h. Upon cooling to 0° C., the reaction mixture was diluted with diethyl ether (50 mL) and the resulting solid was filtered, washed with ether (20 mL), and dried to afford 0.86 g (100%) of (S)-5-(2-(1-amino-2,3-dihydro-1H-inden-4-yl)thiazol-5-yl)-2-isopropoxybenzonitrile hydrochloride 71. LCMS-ESI (m/z) calculated for C22H21N3OS: 375.1; found 376.2 (M+H). tR=2.45 min. 1H NMR (400 MHz, DMSO) δ 8.64 (d, J=3.6 Hz, 2H), 8.30 (d, J=2.3 Hz, 1H), 8.23 (dd, J=8.9, 2.4 Hz, 1H), 8.21 (s, 1H), 7.70 (dd, J=7.6, 2.6 Hz, 2H), 7.45 (dd, J=8.4, 5.4 Hz, 2H), 4.91 (dt, J=12.2, 6.1 Hz, 1H), 4.85-4.58 (m, 1H), 3.36-3.21 (m, 1H), 3.21-3.04 (m, 1H), 2.63-2.51 (m, 1H), 2.09 (td, J=8.3, 2.8 Hz, 1H), 1.43-1.28 (m, 6H). 13C NMR (101 MHz, DMSO) δ 166.61, 166.11, 161.50, 143.05, 141.73, 134.16, 133.45, 129.74, 128.26, 127.84, 126.47, 122.33, 115.79, 115.20, 102.53, 72.43, 54.75, 31.48, 30.12, 21.74. Chiral HPLC: (S)-5-(2-(1-amino-2,3-dihydro-1H-inden-4-yl)thiazol-5-yl)-2-isopropoxybenzonitrile hydrochloride was eluted in 8% EtOH/hexanes: >99.9% ee, tR=67.15 min (Chiral Method 1).

Workup

  1. customPrepared
  2. temperatureUpon cooling to 0° C.
  3. filtrationthe resulting solid was filtered
  4. washwashed with ether (20 mL)
  5. customdried

Sources & evidence

ORD record
ord-cba5660ec094419aadbff5de6a3b28f7
Source dataset
uspto-grants-2013_08
Patent number
US08507538B2

Reaction notes

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