Ammonia → HCID 86698050, compound

HRID 518899Notes

Reaction equation

HRID 518899 reaction equation
Cl.C([N:4]([CH:36]1[CH2:41][CH2:40][N:39]([CH3:42])[CH2:38][CH2:37]1)[C:5]1[CH:10]=[CH:9][C:8]([NH:11][C:12]2[N:13]=[CH:14][C:15]3[S:20][C:19]([C:21]([NH2:23])=[O:22])=[C:18]([C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=4[O:30][CH3:31])[C:16]=3[N:17]=2)=[C:7]([O:32][CH:33]([CH3:35])[CH3:34])[CH:6]=1)=O.N>O>[CH:33]([O:32][C:7]1[CH:6]=[C:5]([NH:4][CH:36]2[CH2:37][CH2:38][N:39]([CH3:42])[CH2:40][CH2:41]2)[CH:10]=[CH:9][C:8]=1[NH:11][C:12]1[N:13]=[CH:14][C:15]2[S:20][C:19]([C:21]([NH2:23])=[O:22])=[C:18]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=3[O:30][CH3:31])[C:16]=2[N:17]=1)([CH3:35])[CH3:34]

Participants

5

Reactant 3

HCID 222AmmoniaHCID 313Hydrochloric Acid2×HCID 86698051HCID 86698051, compound

Product 1

HCID 86698050HCID 86698050, compoundYield 54.7%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A 5N hydrochloric acid solution (6.25 ml) is added to a single-necked round-bottomed flask containing 0.25 g of 2-{4-[formyl-(1-methylpiperidin-4-yl)amino]-2-isopropoxyphenylamino}-7-(2-methoxyphenyl)thieno[3,2-d]pyrimidine-6-carboxamide. The reaction mixture is stirred at ambient temperature for 40 h, and then a further 2.0 ml of 5N hydrochloric acid solution are added and the stirring is continued for 20 h. The mixture is then poured into 25 ml of water and alkalinized by adding a solution of aqueous ammonia at 28% (8 ml). After extraction with ethyl acetate (3×30 ml), the organic extracts are combined, washed with water (3×20 ml) to neutral pH, dried over magnesium sulfate, and then concentrated to dryness under reduced pressure. The residue is purified by chromatography on a 25 g cartridge of 15-40 μm silica, elution being carried out successively with 94/3/3 v/v/v then 90/5/5 v/v/v dichloromethane/methanol/acetonitrile mixtures, and then a dichloromethane/methanol/acetonitrile/28% aqueous ammonia mixture (93/3/3/1 v/v/v/v) at a flow rate of 20 ml/min. The pasty orange solid obtained is triturated from diisopropyl ether and reconcentrated to dryness under reduced pressure, and then triturated from petroleum ether and filtered. The solid obtained is stove-dried under reduced pressure (40° C., 10-3 mbar), so as to obtain 0.13 g of 2-[2-isopropoxy-4-(1-methylpiperidin-4-ylamino)phenylamino]-7-(2-methoxyphenyl)thieno[3,2-d]pyrimidine-6-carboxamide in the form of a dark orange solid.

Workup

  1. waitthe stirring is continued for 20 h
  2. extractionAfter extraction with ethyl acetate (3×30 ml)
  3. washwashed with water (3×20 ml) to neutral pH
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated to dryness under reduced pressure
  6. customThe residue is purified by chromatography on a 25 g cartridge of 15-40 μm silica, elution
  7. customThe pasty orange solid obtained
  8. customis triturated from diisopropyl ether
  9. customtriturated from petroleum ether
  10. filtrationfiltered
  11. customThe solid obtained
  12. customis stove-dried under reduced pressure (40° C., 10-3 mbar)

Sources & evidence

ORD record
ord-e786cce44c2d4048be4e06585bad7638
Source dataset
uspto-grants-2015_08
Patent number
US09115140B2

Reaction notes

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