tert-Butanol → 4-(7-bromo-6-fluoro-3,4-dihydroisoquinolin-2(1H)-yl)-6-(4-methylpiperazin-1-yl)pyrimidin-2-amine

HRID 2090467Notes

Reaction equation

HRID 2090467 reaction equation
[NH2:1][C:2]1[N:7]=[C:6](Cl)[CH:5]=[C:4](Cl)[N:3]=1.Cl.[Br:11][C:12]1[CH:21]=[C:20]2[C:15]([CH2:16][CH2:17][NH:18][CH2:19]2)=[CH:14][C:13]=1[F:22].[CH3:23][N:24]1[CH2:29][CH2:28][N:27](C)[CH2:26][CH2:25]1.C(O)(C)(C)C.CN1CCNCC1>>[Br:11][C:12]1[CH:21]=[C:20]2[C:15]([CH2:16][CH2:17][N:18]([C:4]3[CH:5]=[C:6]([N:27]4[CH2:28][CH2:29][N:24]([CH3:23])[CH2:25][CH2:26]4)[N:7]=[C:2]([NH2:1])[N:3]=3)[CH2:19]2)=[CH:14][C:13]=1[F:22]

Participants

6

Reactant 5

HCID 6386tert-ButanolHCID 78181,4-DimethylpiperazineHCID 531671-MethylpiperazineHCID 655222-Amino-4,6-dichloropyrimidineHCID 674354067-Bromo-6-fluoro-1,2,3,4-tetrahydroisoquinoline hydrochloride

Product 1

HCID 594023364-(7-bromo-6-fluoro-3,4-dihydroisoquinolin-2(1H)-yl)-6-(4-methylpiperazin-1-yl)pyrimidin-2-amineYield 56.2%

Conditions

Temperature
90 °C

Procedure

A mixture of 2-amino-4,6-dichloropyrimidine (0.149 g, 0.908 mmol), 7-bromo-6-fluoro-1,2,3,4-tetrahydroisoquinoline hydrochloride (0.242 g, 0.908 mmol) and, 1,4-dimethylpiperazine (487 uL, 3.63 mmol) in tert-butyl alcohol (2.00 mL, 20.9 mmol) was heated at 90° C. for 2 h. After cooling, 1-methylpiperazine (202 uL, 1.82 mmol) was added. The mixture was heated at 120° C. overnight. After cooling, the volatiles were removed under reduced pressure. The residue was purified by flash chromatography on a silica gel column with methanol in DCM (0-10%) to give the desired product (215 mg, 56.2%). LCMS (M+H)+: m/z=421.1/423.1.

Workup

  1. temperatureAfter cooling
  2. temperatureThe mixture was heated at 120° C. overnight
  3. temperatureAfter cooling
  4. customthe volatiles were removed under reduced pressure
  5. customThe residue was purified by flash chromatography on a silica gel column with methanol in DCM (0-10%)

Sources & evidence

ORD record
ord-af01e659dd914c49929a20c063016f8f
Source dataset
uspto-grants-2013_05
Patent number
US08436008B2

Reaction notes

Loading…