Cesium carbonate → tert-Butyl-2-[(3,4,5-trimethoxyphenyl)amino]-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine-6-carboxylate

HRID 930493Notes

Reaction equation

HRID 930493 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:18][CH2:17][C:11]2[N:12]=[C:13]([NH2:16])[N:14]=[CH:15][C:10]=2[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Br[C:20]1[CH:21]=[C:22]([O:30][CH3:31])[C:23]([O:28][CH3:29])=[C:24]([O:26][CH3:27])[CH:25]=1.CC(C1C=C(C(C)C)C(C2C(P(C3CCCCC3)C3CCCCC3)=C(OC)C=CC=2OC)=C(C(C)C)C=1)C.C(=O)([O-])[O-].[Cs+].[Cs+]>CC(O)(C)C.CCOC(C)=O>[C:1]([O:5][C:6]([N:8]1[CH2:18][CH2:17][C:11]2[N:12]=[C:13]([NH:16][C:20]3[CH:21]=[C:22]([O:30][CH3:31])[C:23]([O:28][CH3:29])=[C:24]([O:26][CH3:27])[CH:25]=3)[N:14]=[CH:15][C:10]=2[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 758855-Bromo-1,2,3-trimethoxybenzeneHCID 25112535BrettphosHCID 29184118tert-butyl 2-amino-5H,6H,7H,8H-pyrido[4,3-d]pyrimidine-6-carboxylate

Product 1

HCID 118970889tert-Butyl-2-[(3,4,5-trimethoxyphenyl)amino]-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine-6-carboxylateYield 79%

Reagents, catalysts & solvents 2

HCID 6386tert-ButanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of 6-t-Butoxycarbonyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-ylamine, Intermediate 3 (500 mg, 2.0 mmol), 5-bromo-1,2,3-trimethoxybenzene (494 mg, 2.0 mmol), Cl-BrettPhos-Pd precatalyst/BrettPhos admixture (53 mg, 0.040 mmol (1:1 mol: mol)) and cesium carbonate (912 mg, 2.80 mmol) in t-BuOH (15 mL) was heated at 110° C. for 16 hours. Upon cooling, the reaction mixture was diluted with EtOAc and the insolubles were filtered off (celite). The filtrate was concentrated and the residue was eluted through a flash column (silica gel 60, 230-400 mesh, 2:3 hexanes:EtOAc) to obtain a clear glass (659 mg, 79%).

Workup

  1. temperatureUpon cooling
  2. filtrationthe insolubles were filtered off (celite)
  3. concentrationThe filtrate was concentrated
  4. washthe residue was eluted through a flash column (silica gel 60, 230-400 mesh, 2:3 hexanes:EtOAc)

Sources & evidence

ORD record
ord-e0cd54631fb746a2a8e50839c507db18
Source dataset
uspto-grants-2016_03
Patent number
US09296747B1

Reaction notes

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