Maleic Acid → HCID 178508611, compound

HRID 51531Notes

Reaction equation

HRID 51531 reaction equation
[NH2:1][C:2]1[C:3]2[C:10]([C:11]3[CH:16]=[CH:15][C:14]([O:17][C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)=[CH:13][CH:12]=3)=[CH:9][N:8]([C@@H:24]3[CH2:29][CH2:28][C@H:27]([N:30]4[CH2:35][CH2:34][N:33](C(OC(C)(C)C)=O)[CH2:32][CH2:31]4)[CH2:26][CH2:25]3)[C:4]=2[N:5]=[CH:6][N:7]=1.FC(F)(F)C(O)=O.ClCCl.[C:53]([OH:60])(=[O:59])/[CH:54]=[CH:55]\[C:56]([OH:58])=[O:57]>C(OCC)(=O)C>[C:53]([OH:60])(=[O:59])/[CH:54]=[CH:55]\[C:56]([OH:58])=[O:57].[C:53]([OH:60])(=[O:59])/[CH:54]=[CH:55]\[C:56]([OH:58])=[O:57].[C:53]([OH:60])(=[O:59])/[CH:54]=[CH:55]\[C:56]([OH:58])=[O:57].[O:17]([C:14]1[CH:15]=[CH:16][C:11]([C:10]2[C:3]3[C:2]([NH2:1])=[N:7][CH:6]=[N:5][C:4]=3[N:8]([C@H:24]3[CH2:29][CH2:28][C@@H:27]([N:30]4[CH2:31][CH2:32][NH:33][CH2:34][CH2:35]4)[CH2:26][CH2:25]3)[CH:9]=2)=[CH:12][CH:13]=1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1

Participants

5

Reactant 3

HCID 444266Maleic AcidHCID 21863450Trifluoroacetic acid methylene chlorideHCID 178452341HCID 178452341, compound

Product 1

HCID 178508611HCID 178508611, compoundYield 959.9%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Procedure

The cis-tert-butyl 4-{4-[4-amino-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl]cyclohexyl}-1-piperazinecarboxylate (1.85 g, 3.27 mmol) was treated with a 20% trifluoroacetic acid/dichloromethane solution (60 ml) and stirred for 30 minutes at ambient temperature. The solvents were removed under reduced pressure then the residue was partitioned between dichloromethane (200 ml) and aqueous saturated sodium bicarbonate solution (30 ml). The organic solution was dried over magnesium sulfate, filtered and the filtrate evaporated to a residue (1.55 g). A portion of this material (1.0 g, 2.15 mmol) was dissolved in warm ethyl acetate (220 ml) then treated with maleic acid (0.75 g, 0.44 mmol) in warm ethyl acetate (75 ml). The mixture was cooled to ambient temperature then the solid was collected by filtration and dried to give Cis-5-(4-phenoxyphenyl)-7-(4-piperazinocyclohexyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine trimaleate salt (1.15 g) as a white solid: 1H NMR (DMSO-d6, 400 MHz) δ 8.5 (bs, 1H), 8.23 (s, 1H), 7.41-7.51 (m, 5H), 7.08-7.19 (m, 5H), 6.65 (bs, 2H), 6.16 (s, 6H), 4.74 (m, 1H), 1.16-3.2 (m, 17H); RP—HPLC (Hypersil CPS, 5 μm, 100 A, 250×4.6 mm; 25-100% acetonitrile-0.1 M ammonium acetate over 10 min, 1 ml/min) tr=8.63 min; MS: MH+469.

Workup

  1. customThe solvents were removed under reduced pressure
  2. customthe residue was partitioned between dichloromethane (200 ml) and aqueous saturated sodium bicarbonate solution (30 ml)
  3. dry with materialThe organic solution was dried over magnesium sulfate
  4. filtrationfiltered
  5. customthe filtrate evaporated to a residue (1.55 g)
  6. temperatureThe mixture was cooled to ambient temperature
  7. filtrationthe solid was collected by filtration
  8. customdried

Sources & evidence

ORD record
ord-4fd5e6260f5f4a20ac80c32dec22c045
Source dataset
uspto-grants-2004_03
Patent number
US06713474B2

Reaction notes

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