Carbamic acid, ethyl ester → Ethyl {2-[2-amino-6-(4-methylpiperazin-1-yl)pyrimidin-4-yl]-1,2,3,4-tetrahydro isoquinolin-7-yl}carbamate

HRID 2090320

Reaction equation

Br[C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][N:8]([C:12]3[CH:17]=[C:16]([N:18]4[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]4)[N:15]=[C:14]([NH2:25])[N:13]=3)[CH2:9]2)=[CH:4][CH:3]=1.CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+].[NH2:74][C:75]([O:77][CH2:78][CH3:79])=[O:76]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[NH2:25][C:14]1[N:13]=[C:12]([N:8]2[CH2:7][CH2:6][C:5]3[C:10](=[CH:11][C:2]([NH:74][C:75](=[O:76])[O:77][CH2:78][CH3:79])=[CH:3][CH:4]=3)[CH2:9]2)[CH:17]=[C:16]([N:18]2[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]2)[N:15]=1

Participants

Conditions

Temperature: 120 °C

Procedure

A mixture of 4-(7-bromo-3,4-dihydroisoquinolin-2(1H)-yl)-6-(4-methylpiperazin-1-yl)pyrimidin-2-amine (22.4 mg, 0.0556 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (12.9 mg, 0.0222 mmol, Aldrich, Cat. No. 526460), palladium acetate (2.50 mg, 0.0111 mmol, Aldrich, Cat. No. 379875), cesium carbonate (36.2 mg, 0.111 mmol) and urethane (7.43 mg, 0.0834 mmol, Aldrich, Cat. No. 418331) in 1,4-dioxane (1 mL) was degassed with nitrogen and then heated at 120° C. for 20 h. The reaction mixture was cooled to r.t. and concentrated under reduced pressure. The residue was dissolved in MeOH and purified by RP-HPLC (pH=10) to afford the desired compound. LCMS (M+H)+: m/z=412.2.

Workup

custom418331) in 1,4-dioxane (1 mL) was degassed with nitrogen
temperatureThe reaction mixture was cooled to r.t.
concentrationconcentrated under reduced pressure
dissolutionThe residue was dissolved in MeOH
custompurified by RP-HPLC (pH=10)

Sources & evidence

ORD record: ord-e44748d54ce24299b476472e316b8d6c
Source dataset: uspto-grants-2013_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08436008B2

Linked notes

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