Hydrochloric Acid → HCID 69180910, compound

HRID 1295653Notes

Reaction equation

HRID 1295653 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].[Cl:7][C:8]1[CH:9]=[C:10]([NH:14][C:15]2[C:16]3[CH:23]=[C:22]([C:24]4[CH:34]=[CH:33][C:27]([C:28]([N:30]([CH3:32])[CH3:31])=O)=[CH:26][CH:25]=4)[NH:21][C:17]=3[N:18]=[CH:19][N:20]=2)[CH:11]=[CH:12][CH:13]=1.[OH-].[Na+].Cl>C1COCC1.CO.O>[ClH:7].[Cl:7][C:8]1[CH:9]=[C:10]([NH:14][C:15]2[C:16]3[CH:23]=[C:22]([C:24]4[CH:34]=[CH:33][C:27]([CH2:28][N:30]([CH3:32])[CH3:31])=[CH:26][CH:25]=4)[NH:21][C:17]=3[N:18]=[CH:19][N:20]=2)[CH:11]=[CH:12][CH:13]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 21226445Aluminium lithium hydrideHCID 23282749HCID 23282749, compound

Product 1

HCID 69180910HCID 69180910, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

Lithium aluminum hydride (72 mg, 1.9 mmol) is suspended in dry THF (12 ml) under a nitrogen atmosphere. Solid 4-[4-(3-chloro-phenylamino)-7H-pyrrolo[2,3-d]pyrimidin-6-yl]-N,N-dimethyl-benzamide (described in WO 97/02266, 140 mg, 0.37 mmol) is added and the mixture heated to 60° C. for 1 h. The reaction mixture is then hydrolized at 0° C. by sequential addition of water (0.072 ml), 15% sodium hydroxide (0.072 ml) and water (0.21 ml). The precipitate is removed by filtration and the filtrate concentrated on a rotary evaporator. The yellow crystalline residue is suspended in methanol, filtered, suspended in toluene, filtered, suspended in methanol again and filtered to give the free base of the title compound [Rf (dichloromethane/methanol 9:1 plus 1 drop of conc. ammonia)=0.36]. This is suspended in methanol (2 ml) and treated with 1 N hydrochloric acid (0.2 ml). The suspension is stirred well and filtered. The crystals are triturated in methanol/water 9:1 and filtered again to give the title compound; m.p. 280-283° C.; MS-ES+: (M+H)+=378.

Workup

  1. customThe precipitate is removed by filtration
  2. concentrationthe filtrate concentrated on a rotary evaporator
  3. filtrationfiltered
  4. filtrationfiltered
  5. filtrationfiltered
  6. customto give the free base of the title compound [Rf (dichloromethane/methanol 9:1 plus 1 drop of conc. ammonia)=0.36]
  7. filtrationfiltered
  8. customThe crystals are triturated in methanol/water 9:1
  9. filtrationfiltered again

Sources & evidence

ORD record
ord-42d55004112c411a81fc9101ad6fe9a3
Source dataset
uspto-grants-2007_07
Patent number
US07244729B2

Reaction notes

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