Triethylamine → 1-(tert-butoxycarbonyl)piperidin-4-yl 7-[2-amino-6-(4-methylpiperazin-1-yl)pyrimidin-4-yl]-3,4-dihydroisoquinoline-2(1H)-carboxylate

HRID 449378Notes

Reaction equation

HRID 449378 reaction equation
[N+](C1C=CC(O[C:9]([O:11][CH:12]2[CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14][CH2:13]2)=[O:10])=CC=1)([O-])=O.Cl.[CH3:28][N:29]1[CH2:34][CH2:33][N:32]([C:35]2[CH:40]=[C:39]([C:41]3[CH:50]=[C:49]4[C:44]([CH2:45][CH2:46][NH:47][CH2:48]4)=[CH:43][CH:42]=3)[N:38]=[C:37]([NH2:51])[N:36]=2)[CH2:31][CH2:30]1.C(N(CC)CC)C>C(#N)C.O>[NH2:51][C:37]1[N:38]=[C:39]([C:41]2[CH:50]=[C:49]3[C:44]([CH2:45][CH2:46][N:47]([C:9]([O:11][CH:12]4[CH2:13][CH2:14][N:15]([C:18]([O:20][C:21]([CH3:22])([CH3:23])[CH3:24])=[O:19])[CH2:16][CH2:17]4)=[O:10])[CH2:48]3)=[CH:43][CH:42]=2)[CH:40]=[C:35]([N:32]2[CH2:31][CH2:30][N:29]([CH3:28])[CH2:34][CH2:33]2)[N:36]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 23536851Tert-butyl 4-(((4-nitrophenoxy)carbonyl)oxy)piperidine-1-carboxylateHCID 675414894-(4-methylpiperazin-1-yl)-6-(1,2,3,4-tetrahydroisoquinolin-7-yl)pyrimidin-2-amine HCl salt

Product 1

HCID 594965731-(tert-butoxycarbonyl)piperidin-4-yl 7-[2-amino-6-(4-methylpiperazin-1-yl)pyrimidin-4-yl]-3,4-dihydroisoquinoline-2(1H)-carboxylateYield 79%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

tert-Butyl 4-{[(4-nitrophenoxy)carbonyl]oxy}piperidine-1-carboxylate (0.093 g, 0.25 mmol) was added to a solution of 4-(4-methylpiperazin-1-yl)-6-(1,2,3,4-tetrahydroisoquinolin-7-yl)pyrimidin-2-amine HCl salt (0.10 g, 0.23 mmol) and triethylamine (0.13 mL, 0.92 mmol) in acetonitrile (5.0 mL). The reaction mixture was stirred at r.t. overnight. The mixture was diluted with water, and extracted with ethyl acetate (3×10 mL). The combined organic layers were dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography on a silica gel column with MeOH in dichloromethane (0-10%) to afford the desired product (0.10 g, 79%). Analytic LCMS (M+H)+: m/z=552.3.

Workup

  1. extractionextracted with ethyl acetate (3×10 mL)
  2. dry with materialThe combined organic layers were dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by flash chromatography on a silica gel column with MeOH in dichloromethane (0-10%)

Sources & evidence

ORD record
ord-d23437a99202423f93c9110689aef4f8
Source dataset
uspto-grants-2013_07
Patent number
US08481732B2

Reaction notes

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