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

HRID 600419Notes

Reaction equation

HRID 600419 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-93d9fe9dd8c9474f894a18719455f2ca
Source dataset
uspto-grants-2011_03
Patent number
US07902187B2

Reaction notes

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