Pyridine → HCID 59648323, compound

HRID 1507618Notes

Reaction equation

HRID 1507618 reaction equation
C(Cl)(=O)C(Cl)=O.CC(C)(C)C([N:11]([CH2:21][CH2:22][O:23][CH3:24])[C:12]1[CH:20]=[CH:19][C:15]([C:16](O)=O)=[CH:14][N:13]=1)=O.[NH2:27][C:28]1[C:29](=[O:42])[N:30]([CH:39]2[CH2:41][CH2:40]2)[C:31](=[O:38])[N:32]([CH2:35][CH2:36][CH3:37])[C:33]=1[NH2:34].N1C=CC=CC=1>C(Cl)Cl.CN(C=O)C>[CH:39]1([N:30]2[C:29](=[O:42])[C:28]3[NH:27][C:16]([C:15]4[CH:14]=[N:13][C:12]([NH:11][CH2:21][CH2:22][O:23][CH3:24])=[CH:20][CH:19]=4)=[N:34][C:33]=3[N:32]([CH2:35][CH2:36][CH3:37])[C:31]2=[O:38])[CH2:41][CH2:40]1

Participants

7

Reactant 4

HCID 1049PyridineHCID 65578Oxalyl chlorideHCID 57883116HCID 57883116, compoundHCID 86704348HCID 86704348, compound

Product 1

HCID 59648323HCID 59648323, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent

Procedure

Oxalyl chloride (0.98 ml, 11.25 mmol, 1.05 eq) was added dropwise to a stirred solution of 6-[(2,2-Dimethyl-propionyl)-(2-methoxy-ethyl)-amino]-nicotinic acid (3 g, 10.71 mmol) in DCM (30 Ml) at 0° C. followed by one drop of DMF. Stirred at that temperature for 30 min before the addition of 5,6-Diamino-3-cyclopropyl-1-propyl-1H-pyrimidine-2,4-dione (2.4 g, 10.71 mmol, 1 eq) and followed by pyridine (0.866 ml, 10.71 mmol, 1 eq). The reaction mixture was allowed to warm to room temperature for 3 hr then the mixture was evaporated to dryness and redissolved in 30 ml of 4N NaOH. The reaction mixture was heated to reflux for a total of 5 hours. After cooling to room temperature, the pH adjusted with aqueous hydrochloric acid to 7-8. Water was evaporated to half volume then ethanol was added at 0° C. and stirred overnight (15 hr). The reaction mixture is filtered and the solid was washed with water and then ethanol. The product is then dried at 50° C. to provide 3.41 g (83%). 1H NMR (400 MHz, DMSO-d6) δ 13.68 (1H), 8.7 (1H), 8.0 (1H), 7.15 (1H), 6.6 (1H), 3.95 (2H), 3.48 (4H), 3.26 (3H), 2.6 (1H), 1.7 (2H), 1.05 (2H), 0.9 (3H), 0.7 (2H); m/z (ES+) 385.44

Workup

  1. customthe mixture was evaporated to dryness
  2. dissolutionredissolved in 30 ml of 4N NaOH
  3. temperatureThe reaction mixture was heated
  4. temperatureto reflux for a total of 5 hours
  5. temperatureAfter cooling to room temperature
  6. customWater was evaporated to half volume
  7. additionethanol was added at 0° C.
  8. filtrationThe reaction mixture is filtered
  9. washthe solid was washed with water
  10. customThe product is then dried at 50° C.
  11. customto provide 3.41 g (83%)

Sources & evidence

ORD record
ord-1f4114dac4c143089fa013f871b762a8
Source dataset
uspto-grants-2015_12
Patent number
US09221821B2

Reaction notes

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