Hydrochloric Acid → [5-(5-{3-cyano-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-3,4-dihydro-2(1H)-isoquinolinyl]acetic acid hydrochloride

HRID 2059947Notes

Reaction equation

HRID 2059947 reaction equation
C(O)=O.C([O:6][C:7](=[O:36])[CH2:8][N:9]1[CH2:18][CH2:17][C:16]2[C:11](=[CH:12][CH:13]=[CH:14][C:15]=2[C:19]2[N:23]=[C:22]([C:24]3[CH:29]=[CH:28][C:27]([O:30][CH:31]([CH3:33])[CH3:32])=[C:26]([C:34]#[N:35])[CH:25]=3)[O:21][N:20]=2)[CH2:10]1)C.[Li+].[OH-].[ClH:39]>C1COCC1.CO.O>[ClH:39].[C:34]([C:26]1[CH:25]=[C:24]([C:22]2[O:21][N:20]=[C:19]([C:15]3[CH:14]=[CH:13][CH:12]=[C:11]4[C:16]=3[CH2:17][CH2:18][N:9]([CH2:8][C:7]([OH:36])=[O:6])[CH2:10]4)[N:23]=2)[CH:29]=[CH:28][C:27]=1[O:30][CH:31]([CH3:33])[CH3:32])#[N:35]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 131729974Ethyl[5-(5-{3-cyano-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-3,4-dihydro-2(1H)-isoquinolinyl]acetate formic acid

Product 1

HCID 68500104[5-(5-{3-cyano-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-3,4-dihydro-2(1H)-isoquinolinyl]acetic acid hydrochlorideYield 85%

Reagents, catalysts & solvents 1

HCID 21892291Methanol tetrahydrofuran waterSolvent

Procedure

A solution of ethyl[5-(5-{3-cyano-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-3,4-dihydro-2(1H)-isoquinolinyl]acetate formic acid salt (Preparation 5, 11.6 mg, 0.026 mmol) and LiOH (0.3 mg) in THF-MeOH-water (300 μl, 300 μl, 200 μL) was irradiated to 100° C. for 3 min in the microwave. 2M aqueous HCl (1 mL) was added, then the solution extracted with DCM (2×2 mL). The combined organics were concentrated in vacuo to give the title compound as a white solid (10.1 mg, 85%). 1H NMR (400 MHz, d4-MeOH) δ 8.48 (1H, d), 8.44 (1H, dd), 8.21 (1H, d), 7.44 (1H, t), 7.47 (2H, apparent d), 4.97 (1H, sept), 4.70 (2H, s), 4.32 (2H, s), 3.67 (2H, t), 3.57 (2H, t), 1.47 (6H, d); m/z (ES) 419 [M+H]+.

Workup

  1. extractionthe solution extracted with DCM (2×2 mL)
  2. concentrationThe combined organics were concentrated in vacuo

Sources & evidence

ORD record
ord-9803ccc5b65549be8b4c20e0b9ec993b
Source dataset
uspto-grants-2012_10
Patent number
US08278324B2

Reaction notes

Loading…