Pyridine → HCID 136069599, compound

HRID 2278611Notes

Reaction equation

HRID 2278611 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl.CN(C)CCCN=C=NCC.N1(C2N=C(CC(=O)N3[C:41]4[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=4)[C:35]4([CH2:43][CH2:42]4)C3)NC(=O)C=2)CCOCC1.[N:46]1([C:52]2[N:53]=[C:54]([CH2:59][C:60]([O-:62])=O)[NH:55][C:56](=[O:58])[CH:57]=2)[CH2:51][CH2:50][O:49][CH2:48][CH2:47]1.[Na+]>CN(C)C=O>[N:46]1([C:52]2[N:53]=[C:54]([CH2:59][C:60](=[O:62])[N:1]3[C:3]4[C:4](=[C:35]([C:36]5[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=5)[CH:42]=[CH:43][CH:2]=4)[CH2:5][CH2:6]3)[NH:55][C:56](=[O:58])[CH:57]=2)[CH2:47][CH2:48][O:49][CH2:50][CH2:51]1

Participants

6

Reactant 4

HCID 1049PyridineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 136041844Sodium (4-morpholin-4-yl-6-oxo-1,6-dihydropyrimidin-2-yl)acetateHCID 136069598HCID 136069598, compound

Product 1

HCID 136069599HCID 136069599, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

0.16 ml of pyridine, 240 mg of N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride and 210 mg of 4-phenyl-2,3-dihydro-1H-indole (reference example 1d) are successively added to a suspension of 250 mg of sodium [4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetate (example 1d, step 2d) in 5 ml of N,N-dimethylformamide. The reaction mixture is stirred at ambient temperature for 15 hours, and is then concentrated to dryness under reduced pressure. The residue is taken up in and triturated from 30 ml of water, and then the precipitate formed is filtered off and then solubilized in a 90/10 dichloromethane/methanol mixture and, finally, concentrated to dryness under reduced pressure. The residue is purified by chromatography on a 30 g column of 20-45 μm silica, elution being carried out with a mixture of dichloromethane and methanol (90/10: v/v). The fractions containing the expected product are concentrated to dryness under reduced pressure and the residue is triturated from 20 ml of diisopropyl ether. The solid obtained is filtered off and then dried under reduced pressure at 40° C. 232 mg of 6-(morpholin-4-yl)-2-[2-oxo-2-(4-phenyl-2,3-dihydro-1H-indol-1-yl)ethyl]pyrimidin-4(3H)-one are thus obtained in the form of a pink solid, the characteristics of which are the following:

Workup

  1. concentrationis then concentrated to dryness under reduced pressure
  2. customtriturated from 30 ml of water
  3. customthe precipitate formed
  4. filtrationis filtered off
  5. concentrationfinally, concentrated to dryness under reduced pressure
  6. customThe residue is purified by chromatography on a 30 g column of 20-45 μm silica, elution
  7. additionbeing carried out with a mixture of dichloromethane and methanol (90/10: v/v)
  8. additionThe fractions containing the expected product
  9. concentrationare concentrated to dryness under reduced pressure
  10. customthe residue is triturated from 20 ml of diisopropyl ether
  11. customThe solid obtained
  12. filtrationis filtered off
  13. customdried under reduced pressure at 40° C

Sources & evidence

ORD record
ord-2559abf0417a4195813c41675dc4f34e
Source dataset
uspto-grants-2015_09
Patent number
US09133168B2

Reaction notes

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