Dimethylamine → HCID 69179733, compound

HRID 2252771Notes

Reaction equation

HRID 2252771 reaction equation
Cl[CH2:2][C:3]([NH:5][CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([C:13]2[NH:30][C:16]3[N:17]=[CH:18][N:19]=[C:20]([NH:21][C:22]4[CH:27]=[CH:26][C:25]([F:28])=[C:24]([Cl:29])[CH:23]=4)[C:15]=3[CH:14]=2)[CH:8]=1)=[O:4].[CH3:31][NH:32][CH3:33]>O1CCOCC1.C(O)C>[Cl:29][C:24]1[CH:23]=[C:22]([NH:21][C:20]2[C:15]3[CH:14]=[C:13]([C:9]4[CH:8]=[C:7]([CH:12]=[CH:11][CH:10]=4)[CH2:6][NH:5][C:3](=[O:4])[CH2:2][N:32]([CH3:33])[CH3:31])[NH:30][C:16]=3[N:17]=[CH:18][N:19]=2)[CH:27]=[CH:26][C:25]=1[F:28]

Participants

5

Reactant 2

HCID 674DimethylamineHCID 69183775HCID 69183775, compound

Product 1

HCID 69179733HCID 69179733, compound

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

2-Chloro-N-{3-[4-(3-chloro-4-fluoro-phenylamino)-7H-pyrrolo[2,3-d]pyrimidin-6-yl]-benzyl}-acetamide (120 mg, 0.222 mmol) in 2 ml dioxane and 0.145 ml (0.81 mmol) 5.6 N dimethylamine in ethanol (Fluka, Buchs, Switzerland) is stirred and heated to 100° C. for 4.5 h. The mixture is cooled and the solvent evaporated. The residue is shaken with THF (5 ml), dichloromethane (3 ml), methanol (2 ml) and saturated sodium bicarbonate (2 ml). The two clear layers are separated and the organic phase is treated with 1 g silica gel. The solution containing the silica gel is evaporated and the solid put on top of a flash chromatography column containing 33 g of silica gel. The column is eluted using a mixture of dichloromethane/methanol with gradually increasing concentrations of methanol starting with 100:2.5 and ending with 100:5 and then switching to dichloromethane/methanol/conc. ammonia starting with 100:5:0.25 and ending with 100:10:0.5. The title compound is obtained as colorless crystals; m.p. 272-273° C.; MS-ES+: (M+H)+=453.

Workup

  1. temperatureThe mixture is cooled
  2. customthe solvent evaporated
  3. customThe two clear layers are separated
  4. additionthe organic phase is treated with 1 g silica gel
  5. additionThe solution containing the silica gel
  6. customis evaporated
  7. additionthe solid put on top of a flash chromatography column containing 33 g of silica gel
  8. washThe column is eluted
  9. additiona mixture of dichloromethane/methanol
  10. temperaturewith gradually increasing concentrations of methanol starting with 100:2.5

Sources & evidence

ORD record
ord-cb00d0bad8a6419f940b2d377b382cfd
Source dataset
uspto-grants-2008_01
Patent number
US07323469B2

Reaction notes

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