Potassium Carbonate → 4-chloro-7-(2-(4-(2,4-difluorophenyl)piperazin-1-yl)ethyl)-7H-pyrrolo[2,3-d]pyrimidin-2-amine

HRID 2239813Notes

Reaction equation

HRID 2239813 reaction equation
Br[CH2:2][CH2:3][N:4]1[C:8]2[N:9]=[C:10]([NH2:14])[N:11]=[C:12]([Cl:13])[C:7]=2[CH:6]=[CH:5]1.[F:15][C:16]1[CH:21]=[C:20]([F:22])[CH:19]=[CH:18][C:17]=1[N:23]1[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]1.C(=O)([O-])[O-].[K+].[K+]>CC(C)=O>[Cl:13][C:12]1[C:7]2[CH:6]=[CH:5][N:4]([CH2:3][CH2:2][N:26]3[CH2:25][CH2:24][N:23]([C:17]4[CH:18]=[CH:19][C:20]([F:22])=[CH:21][C:16]=4[F:15])[CH2:28][CH2:27]3)[C:8]=2[N:9]=[C:10]([NH2:14])[N:11]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 27346371-(2,4-Difluorophenyl)piperazineHCID 866234677-(2-bromoethyl)-4-chloro-7H-pyrrolo[2,3-d]pyrimidin-2-amine

Product 1

HCID 866234694-chloro-7-(2-(4-(2,4-difluorophenyl)piperazin-1-yl)ethyl)-7H-pyrrolo[2,3-d]pyrimidin-2-amine

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of the title A compound in Example 29, 7-(2-bromoethyl)-4-chloro-7H-pyrrolo[2,3-d]pyrimidin-2-amine (225 mg, 0.817 mmol) and 1-(2,4-difluorophenyl)piperazine (193 mg, 0.976 mmol) in 1 mL of dry acetone is added potassium carbonate (322 mg, 2.44 mmol). The mixture is heated at 50° C. for 24 h, cooled to RT, concentrated in vacuo, and the residue taken up in water. The aqueous mixture is repeatedly extracted with EtOAc, and the combined organic extracts are dried (Na2SO4), filtered and evaporated to dryness. The residue is purified by column chromatography on silica gel, eluting with 2% MeOH in DCM to afford 4-chloro-7-(2-(4-(2,4-difluorophenyl)piperazin-1-yl)ethyl)-7H-pyrrolo[2,3-d]pyrimidin-2-amine as a yellow solid: 1H NMR (CDCl3) δ 2.68 (m, 4H), 2.77 (t, 2H, J=8.0 Hz), 3.01 (m, 4H), 4.19 (t, 2H, J=8.0 Hz), 4.88 (brs, 2H), 6.36 (d, 1H, J=4.0 Hz), 6.77-6.87 (m, 3H), 6.96 (d, 1H, J=4.0 Hz).

Workup

  1. temperaturecooled to RT
  2. concentrationconcentrated in vacuo
  3. extractionThe aqueous mixture is repeatedly extracted with EtOAc
  4. dry with materialthe combined organic extracts are dried (Na2SO4)
  5. filtrationfiltered
  6. customevaporated to dryness
  7. customThe residue is purified by column chromatography on silica gel
  8. washeluting with 2% MeOH in DCM

Sources & evidence

ORD record
ord-f8d7525f187445d9862aa1ac02dd55d7
Source dataset
uspto-grants-2010_05
Patent number
US07723343B2

Reaction notes

Loading…