Methylamine → 6-chloro-N4-methylpyrimidine-4,5-diamine

HRID 528025Notes

Reaction equation

HRID 528025 reaction equation
O1CCOCC1.[Cl:7][CH:8]1[C:13](Cl)([NH2:14])[CH:12]=[N:11][CH:10]=[N:9]1.[CH3:16][NH2:17]>O>[Cl:7][C:8]1[N:9]=[CH:10][N:11]=[C:12]([NH:17][CH3:16])[C:13]=1[NH2:14]

Participants

5

Reactant 3

HCID 6329MethylamineHCID 312751,4-DioxaneHCID 667998474,5-Dichloropyrimdine-5-amine2×

Product 1

HCID 3084776-chloro-N4-methylpyrimidine-4,5-diamineYield 98.4%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Procedure

A 50 mL 3-necked flask fitted with a thermometer was charged with 1,4-dioxane (20 mL) and 4,5-dichloropyrimdine-5-amine (5.00 g, 30.5 mmol). The reaction mixture was then stirred for 30 minutes at room temperature to ensure complete dissolution of the 4,5-dichloropyrimidine-5-amine, after which a solution of methylamine in water (40% by weight, 120 mmol, 9.3 mL) was added over a period of 30 minutes by means of a pressure-equalized dropping funnel. Upon completion of addition, the dropping funnel was replaced with a reflux condenser. The stirred reaction mixture was then heated to 75° C. over a period of 40 minutes, and the progress was monitored by LCMS. The reaction was complete after 16 hours. The resulting mixture was then cooled to 50° C. and poured into 120 mL of ice and water (approximetely 1:1 by volume), which resulted in the rapid precipitation of a solid. The resulting suspension was then for a period of 2 hours. The precipitated solids were collected by vacuum filtration, washed with ice-cold water (20 mL) and dried on the filter to give 4.76 g (98.4% yield) of 6-chloro-N4-methylpyrimidine-4,5-diamine as a light yellow solid. This material was submitted to the next step without further purification. 1H-NMR (400 MHz, DMSO-d6): δ 7.73 (s, 1H), 6.87 (d, 1H), 4.94 (broad s, 2H), 2.86 (d, 3H). MS (EI) for C5H7ClN4: 159 (MH+).

Workup

  1. customA 50 mL 3-necked flask fitted with a thermometer
  2. additionUpon completion of addition
  3. customthe dropping funnel was replaced with a reflux condenser
  4. customThe stirred reaction mixture
  5. temperaturewas then heated to 75° C. over a period of 40 minutes
  6. waitThe reaction was complete after 16 hours
  7. temperatureThe resulting mixture was then cooled to 50° C.
  8. customresulted in the rapid precipitation of a solid
  9. waitfor a period of 2 hours
  10. filtrationThe precipitated solids were collected by vacuum filtration
  11. washwashed with ice-cold water (20 mL)
  12. customdried on the
  13. filtrationfilter

Sources & evidence

ORD record
ord-e5b39228715a456bbe3ca36555982f17
Source dataset
uspto-grants-2016_05
Patent number
US09346807B2

Reaction notes

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