Acetic Acid → HCID 66748400, compound

HRID 2402145Notes

Reaction equation

HRID 2402145 reaction equation
[C:1]([C:3]1[C:4]([CH2:18][C:19]2[CH:28]=[C:27]3[C:22]([CH:23]=[CH:24][N:25]=[CH:26]3)=[CH:21][CH:20]=2)=[C:5]([C:14]([O:16]C)=[O:15])[S:6][C:7]=1[N:8]1[CH2:13][CH2:12][O:11][CH2:10][CH2:9]1)#[N:2].O1CCCC1.[OH-].[Na+].O.CO.C(O)(=O)C>>[C:1]([C:3]1[C:4]([CH2:18][C:19]2[CH:28]=[C:27]3[C:22]([CH:23]=[CH:24][N:25]=[CH:26]3)=[CH:21][CH:20]=2)=[C:5]([C:14]([OH:16])=[O:15])[S:6][C:7]=1[N:8]1[CH2:9][CH2:10][O:11][CH2:12][CH2:13]1)#[N:2]

Participants

7

Reactant 6

HCID 176Acetic AcidHCID 887MethanolHCID 962Water2×HCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 66747718HCID 66747718, compound

Product 1

HCID 66748400HCID 66748400, compoundYield 60.5%

Procedure

To the solution of methyl 4-cyano-3-(isoquinolin-7-ylmethyl)-5-(morpholin-4-yl)thiophene-2-carboxylate (0.103 g, 0.246 mmol) in tetrahydrofuran (15.0 mL, 185 mmol) was added 1.00 M of sodium hydroxide in water (3.80 mL, 3.80 mmol), followed by water (4.0 mL, 220 mmol) and methanol (4.0 mL, 99 mmol). The homogeneous solution was stirred at room temperature for 18 hours. Acetic acid (270 mg, 4.5 mmol) was added and the mixture was concentrated in rotavapor. The residue was dissolved in DCM-MeOH and then concentrated with celite. The mixture was loaded in a cartridge and chromatographed in a silica gel column using AcOH/MeOH/DCM (0/0/100 to 0.5/4.5/95) to afford a white solid product (56.5 mg, yield 60.3%). LC/MS: (FA) ES+ 380; ES− 378. 1H NMR (400 MHz, d-chloroform) δ 9.23 (s, 1H), 8.45 (d, J=5.77 Hz, 1H), 7.90 (d, J=8.53 Hz, 1H), 7.84 (s, 1H), 7.76 (d, J=5.77 Hz, 1H), 7.65 (dd, J=8.53, 1.76 Hz, 1H), 4.53 (s, 2H), 3.72 (m, 4H), 3.52 (m, 4H).

Workup

  1. concentrationthe mixture was concentrated in rotavapor
  2. dissolutionThe residue was dissolved in DCM-MeOH
  3. concentrationconcentrated with celite
  4. customchromatographed in a silica gel column

Sources & evidence

ORD record
ord-f7f56479f3a5452fa8b3d1246eee364e
Source dataset
uspto-grants-2014_08
Patent number
US08796271B2

Reaction notes

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