Methyl iodide → HCID 59239421, compound

HRID 1697961Notes

Reaction equation

HRID 1697961 reaction equation
[Cl:1][C:2]1[N:3]=[C:4]([N:19]2[CH2:24][CH2:23][O:22][CH2:21][CH2:20]2)[C:5]2[CH2:11][CH2:10][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:8][C:6]=2[N:7]=1.[C:25]([Li])(C)(C)C.CI>O1CCCC1.CCCCC>[Cl:1][C:2]1[N:3]=[C:4]([N:19]2[CH2:24][CH2:23][O:22][CH2:21][CH2:20]2)[C:5]2[CH2:11][CH2:10][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH:8]([CH3:25])[C:6]=2[N:7]=1

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 59239183HCID 59239183, compoundHCID 178418306HCID 178418306, compound

Product 1

HCID 59239421HCID 59239421, compoundYield 87%

Reagents, catalysts & solvents 2

HCID 8003PentaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of tert-butyl 2-chloro-4-morpholino-5,6-dihydropyrido[3,4-d]pyrimidine-7(8H)-carboxylate (dp) (501 mg, 1.41 mmol) in Tetrahydrofuran (14 mL) was added 1.7 M of tert-Butyllithium in Pentane (1.1 mL) at −78° C., which resulted orange color solution. The reaction was kept at −78° C. for 40 min before Methyl iodide (0.44 mL, 7.1 mmol) was injected. The solution was kept at −78° C. for another 40 min before quenching with water. The mixture was diluted by Dichloromethane, which was washed by water and brine till pH 7. After evaporation, the residue was purified on a silica gel column. Tert-butyl 2-chloro-8-methyl-4-morpholino-5,6-dihydropyrido[3,4-d]pyrimidine-7(8H)-carboxylate (qe) (452 mg, 87% yield) was obtained as white solid: 1H NMR (500 MHz, CDCl3) δ 5.02 (bs, 1H), 4.26 (bs, 1H), 3.91-3.79 (m, 2H), 3.79-3.67 (m, 2H), 3.61 (m, 2H), 3.36 (m, 2H), 2.89 (bs, 1H), 2.75 (bs, 1H), 2.46 (d, J=15.0 Hz, 1H), 1.50 (d, J=7.0 Hz, 3H), 1.48 (s, 9H); LC-MS m/z=369 (M+H). Tert-butyl 2-chloro-8,8-dimethyl-4-morpholino-5,6-dihydropyrido[3,4-d]pyrimidine-7(8H)-carboxylate (qf) (44 mg, 8% yield) was obtained as white solid: 1H NMR (400 MHz, CDCl3) δ 3.87-3.73 (m, 4H), 3.60-3.52 (m, 2H), 3.52-3.42 (m, 4H), 2.65-2.56 (m, 2H), 1.74 (s, 6H), 1.50 (s, 9H); LC-MS m/z=383 (M+H).

Workup

  1. customwhich resulted orange color solution
  2. custombefore quenching with water
  3. additionThe mixture was diluted by Dichloromethane, which
  4. washwas washed by water and brine till pH 7
  5. customAfter evaporation
  6. customthe residue was purified on a silica gel column

Sources & evidence

ORD record
ord-8774e22070a648a4a5eb4bb19b22bb71
Source dataset
uspto-grants-2012_04
Patent number
US08163763B2

Reaction notes

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