Dichloromethane → tert-butyl 7-[2-amino-6-(4-methylpiperazin-1-yl)pyrimidin-4-yl]-6-fluoro-3,4-dihydroisoquinoline-2(1H)-carboxylate

HRID 449390Notes

Reaction equation

Cl[C:2]1[CH:7]=[C:6]([N:8]2[CH2:13][CH2:12][N:11]([CH3:14])[CH2:10][CH2:9]2)[N:5]=[C:4]([NH2:15])[N:3]=1.[F:16][C:17]1[CH:18]=[C:19]2[C:24](=[CH:25][C:26]=1B1OC(C)(C)C(C)(C)O1)[CH2:23][N:22]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:21][CH2:20]2.ClCCl.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O.CO>[NH2:15][C:4]1[N:3]=[C:2]([C:26]2[CH:25]=[C:24]3[C:19]([CH2:20][CH2:21][N:22]([C:36]([O:38][C:39]([CH3:41])([CH3:40])[CH3:42])=[O:37])[CH2:23]3)=[CH:18][C:17]=2[F:16])[CH:7]=[C:6]([N:8]2[CH2:13][CH2:12][N:11]([CH3:14])[CH2:10][CH2:9]2)[N:5]=1

Participants

Conditions

Temperature: 105 °C

Procedure

A mixture of 4-chloro-6-(4-methylpiperazin-1-yl)pyrimidin-2-amine (0.045 g, 0.20 mmol), tert-butyl 6-fluoro-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxylate (0.15 g, 0.20 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (1:1) (0.008 g, 0.01 mmol) and potassium carbonate (0.082 g, 0.60 mmol) in 1,4-dioxane (1 mL) and water (0.5 mL) was heated at 105° C. overnight. After cooled to r.t., the mixture was diluted with MeOH, filtered, and concentrated. The residue was purified by RP-LCMS (pH=10) to afford the desired product. Analytic LCMS (M+H)+: m/z=443.2.

Workup

temperatureAfter cooled to r.t.
filtrationfiltered
concentrationconcentrated
customThe residue was purified by RP-LCMS (pH=10)

Sources & evidence

ORD record: ord-74255c7c6030498d9c275101ac809aff
Source dataset: uspto-grants-2013_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08481732B2

Reaction notes

Loading…