2,5-Diamino-4,6-dichloropyrimidine → (R)-6-chloro-N4-(8-fluorochroman-4-yl)pyrimidine-2,4,5-triamine

HRID 2074170Notes

Reaction equation

HRID 2074170 reaction equation
[NH2:1][C:2]1[N:7]=[C:6](Cl)[C:5]([NH2:9])=[C:4]([Cl:10])[N:3]=1.Cl.[F:12][C:13]1[CH:14]=[CH:15][CH:16]=[C:17]2[C:22]=1[O:21][CH2:20][CH2:19][C@H:18]2[NH2:23].C(=O)(O)[O-].[Na+]>C(O)CCC>[Cl:10][C:4]1[N:3]=[C:2]([NH2:1])[N:7]=[C:6]([NH:23][C@H:18]2[C:17]3[C:22](=[C:13]([F:12])[CH:14]=[CH:15][CH:16]=3)[O:21][CH2:20][CH2:19]2)[C:5]=1[NH2:9]

Participants

5

Reactant 3

HCID 3010392,5-Diamino-4,6-dichloropyrimidineHCID 516892Sodium BicarbonateHCID 52911303(R)-8-fluorochroman-4-amine hydrochloride

Product 1

HCID 57612657(R)-6-chloro-N4-(8-fluorochroman-4-yl)pyrimidine-2,4,5-triamineYield 78%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Procedure

2,5-diamino-4,6-dichloropyrimidine (1.5 g, 8.37 mmol), (R)-8-fluorochroman-4-amine hydrochloride (see preparation below) (1.7 g, 8.37 mmol, 1 equiv.), sodium bicarbonate (2.46 g, 29.3 mmol, 3.5 equiv.) and 1-butanol (30 mL) were heated together at 150° C. in a sealed tube. After 3 days, when the reaction appeared to be complete (by HPLC), the reaction mixture was cooled to room temperature and the solvent was removed in vacuo. The residue was purified by flash chromatography (silica gel, elution with 1/1 ethyl acetate/methylene chloride) to give 2.01 g (78% yield) of the desired product as a yellow solid. 1H NMR (300 MHz, CD3OD) δ, ppm: 6.97-6.86 (m, 2H), 6.77-6.72 (m, 1H), 5.36 (m, 1H), 4.25 (m, 2H), 2.10 (m, 2H); MS (EI) m/z 310.1 (MH)+.

Workup

  1. customthe solvent was removed in vacuo
  2. customThe residue was purified by flash chromatography (silica gel, elution with 1/1 ethyl acetate/methylene chloride)

Sources & evidence

ORD record
ord-13b037e95051472693e47ebebcd3adb5
Source dataset
uspto-grants-2011_04
Patent number
US07919490B2

Reaction notes

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