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Chloroacetone → [6,8-Dimethoxy-4-(4-methyl-thiazol-2-ylamino)isoquinolin-1-ylmethyl]carbamic acid tert-butyl ester

HRID 14648
Notes
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Reaction equation

HRID 14648 reaction equation
[C:1]([O:5][C:6](=[O:27])[NH:7][CH2:8][C:9]1[C:18]2[C:13](=[CH:14][C:15]([O:21][CH3:22])=[CH:16][C:17]=2[O:19][CH3:20])[C:12]([NH:23][C:24]([NH2:26])=[S:25])=[CH:11][N:10]=1)([CH3:4])([CH3:3])[CH3:2].Cl[CH2:29][C:30](=O)[CH3:31].[O-]S([O-])(=O)=O.[Mg+2]>CC(C)=O>[C:1]([O:5][C:6](=[O:27])[NH:7][CH2:8][C:9]1[C:18]2[C:13](=[CH:14][C:15]([O:21][CH3:22])=[CH:16][C:17]=2[O:19][CH3:20])[C:12]([NH:23][C:24]2[S:25][CH:29]=[C:30]([CH3:31])[N:26]=2)=[CH:11][N:10]=1)([CH3:4])([CH3:2])[CH3:3]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

5

Reactant 3

HCID 6571ChloroacetoneHCID 24083Sulfuric acid magnesium salt (1:1)HCID 59341068(6,8-Dimethoxy-4-thioureido-isoquinolin-1-ylmethyl)carbamic acid tert-butyl ester

Product 1

HCID 59341088[6,8-Dimethoxy-4-(4-methyl-thiazol-2-ylamino)isoquinolin-1-ylmethyl]carbamic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 180
Acetone
Solvent

Conditions

Temperature
60 °C

Procedure

To solution of (6,8-dimethoxy-4-thioureido-isoquinolin-1-ylmethyl)carbamic acid tert-butyl ester (50 mg, 0.127 mmol) and chloroacetone (16.1 mg, 0.166 mmol) in acetone (1.4 mL) was added MgSO4 (7.7 mg, 0.0637 mmol). The resulting suspension was stirred at 60° C. and for 4.5 h. The reaction was cooled and concentrated. The residue passed through a 5 g silica cartridge, eluting with 2% MeOH in DCM, to give [6,8-dimethoxy-4-(4-methyl-thiazol-2-ylamino)isoquinolin-1-ylmethyl]carbamic acid tert-butyl ester as a yellow solid (21.3 mg; 39%). 1H-NMR (CDCl3): δ, 8.59 (s, 1H), 7.00 (s, 1H), 6.76 (s, 1H), 6.61 (d, 1H, J=2.2 Hz), 6.13 (s, 1H), 5.05 (d, 2H, J=4.3 Hz), 3.99 (s, 3H), 3.92 (s, 3H), 2.32 (s, 3H), 1.51 (s, 9H); MS: calculated for C21H26N4O4S+H 431.0; found: 431.0.

Workup

  1. temperatureThe reaction was cooled
  2. concentrationconcentrated
  3. washeluting with 2% MeOH in DCM

Sources & evidence

ORD record
ord-7208aacaf7be4988ae1fcbc72e2cd057
Source dataset
uspto-grants-2010_06
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07732446B1

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes