Acetyl chloride → (S)-N-(4-(5-(3-cyano-4-isopropoxyphenyl)-1,3,4-thiadiazol-2-yl)-2,3-dihydro-1H-inden-1-yl)acetamide

HRID 1891466Notes

Reaction equation

HRID 1891466 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(N(CC)CC)C.[C:36](Cl)(=[O:38])[CH3:37]>C(Cl)Cl>[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][C:36](=[O:38])[CH3:37])=[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 6367Acetyl chlorideHCID 8471TriethylamineHCID 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 53233550(S)-N-(4-(5-(3-cyano-4-isopropoxyphenyl)-1,3,4-thiadiazol-2-yl)-2,3-dihydro-1H-inden-1-yl)acetamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Prepared using General Procedure 7: To a stirred solution of (S)-5-(5-(1-amino-2,3-dihydro-1H-inden-4-yl)-1,3,4-thiadiazol-2-yl)-2-isopropoxybenzonitrile hydrochloride 4 (15 mg, 0.03 mmol) in anhydrous DCM (1 mL) was added triethylamine (11 mg, 0.1 mmol) followed by acetyl chloride (4.2 mg, 0.05 mmol) and the reaction mixture was stirred at room temperature overnight. The solvent was evaporated and the crude mixture purified by preparative HPLC to afford (S)-N-(4-(5-(3-cyano-4-isopropoxyphenyl)-1,3,4-thiadiazol-2-yl)-2,3-dihydro-1H-inden-1-yl)acetamide 14. LCMS-ESI (m/z) calculated for: C23H22N4O2S: 418.2; found 419.3 [M+H]+, tR=3.34 min. 1H NMR (400 MHz, CDCl3) δ 8.20 (dd, J=8.9, 2.3 Hz, 1H), 8.13 (d, J=2.2 Hz, 1H), 7.81 (d, J=7.6 Hz, 1H), 7.45 (d, J=7.5 Hz, 1H), 7.36 (t, J=7.6 Hz, 1H), 7.08 (d, J=9.0 Hz, 1H), 5.83 (d, J=8.4 Hz, 1H), 5.57 (q, J=7.9 Hz, 1H), 4.76 (dt, J=12.2, 6.1 Hz, 1H), 3.46 (ddd, J=17.1, 8.8, 3.8 Hz, 1H), 3.28-3.15 (m, 1H), 2.75-2.62 (m, 1H), 2.07 (s, 3H), 1.98-1.80 (m, 1H), 1.46 (d, J=6.1 Hz, 6H). 13C NMR (101 MHz, CDCl3) δ 170.36, 167.43, 166.14, 162.16, 145.92, 142.83, 133.89, 133.77, 129.44, 128.23, 127.18, 126.95, 123.21, 116.05, 114.36, 104.23, 73.03, 55.00, 34.03, 31.95, 23.92, 22.24.

Workup

  1. customPrepared
  2. customThe solvent was evaporated
  3. customthe crude mixture purified by preparative HPLC

Sources & evidence

ORD record
ord-5b03267205af4342b2ed5bb0c3e164eb
Source dataset
uspto-grants-2013_08
Patent number
US08507538B2

Reaction notes

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