Reaction #42973

Reaction equation

Methylamine

Oxalyl chloride

solution

2-[1-(1,3-Dioxo-1,3-dihydro-isoindol-2-ylmethyl)-6,8-dimethoxy-isoquinolin-4-ylamino]-thiazole-4-carboxylic acid

DMF

→

title compound

Yield 60.0%

2-(1-Aminomethyl-6,8-dimethoxy-isoquinolin-4-ylamino)-thiazole-4-carboxylic acid methylamide

Yield 60.0%

Solvents

dichloromethane

Conditions

Workup

1. 1
   workup.STIRRINGthe reaction stirred for 30 min
2. 2
   WashOrganics were washed with brine
3. 3
   Dryingdried (MgSO4)
4. 4
   Concentrationconcentrated
5. 5
   workup.STIRRINGstirring for 1 h
6. 6
   OtherPurification by Prep-HPLC

Procedure

Oxalyl chloride (8 μL, 0.092 mmol) was added to a solution of Example 49A (30 mg, 0.061 mmol) in dichloromethane (4 mL). Catalytic DMF was added, and the reaction stirred for 1 h. Methylamine (180 μL, 2M in THF, 0.366 mmol) was added, and the reaction stirred for 30 min. Organics were washed with brine, dried (MgSO4) and concentrated. Deprotection was carried out with hydrazine (0.2 mL) in methanol (3 mL), stirring for 1 h. Purification by Prep-HPLC gave 17.8 mg (60%) of the title compound (TFA salt) as a yellow solid. H1-NMR (MeOD-d4): δ 9.16 (s, 1H), 7.51 (s, 1H), 7.18 (s, 1H), 6.86 (s, 1H), 4.83 (s, 2H), 4.05 (s, 3H), 3.98 (s, 3H), 2.91 (s, 3H). MS (ES) (M+H) calc'd for C17H19N5O3S, 374; found 374.

Source