Potassium Hydroxide → HCID 178456216, compound

HRID 1014440Notes

Reaction equation

HRID 1014440 reaction equation
[F:1][C:2]1[CH:10]=[C:9]([F:11])[CH:8]=[C:7]([NH:12][C:13]2[C:14]3[CH:39]=[CH:38][N:37](S(C4C=CC(C)=CC=4)(=O)=O)[C:15]=3[N:16]=[C:17]([NH:19][C:20]3[CH:25]=[CH:24][C:23]([CH:26]4[CH2:31][CH2:30][N:29]([CH2:32][CH2:33][CH3:34])[CH2:28][CH2:27]4)=[CH:22][C:21]=3[O:35][CH3:36])[N:18]=2)[C:3]=1[C:4]([NH2:6])=[O:5].[OH-].[K+]>O1CCCC1.O1CCOCC1.O>[F:1][C:2]1[CH:10]=[C:9]([F:11])[CH:8]=[C:7]([NH:12][C:13]2[N:18]=[C:17]([NH:19][C:20]3[CH:25]=[CH:24][C:23]([CH:26]4[CH2:31][CH2:30][N:29]([CH2:32][CH2:33][CH3:34])[CH2:28][CH2:27]4)=[CH:22][C:21]=3[O:35][CH3:36])[NH:16][C:15]3=[N:37][CH:38]=[CH:39][C:14]=23)[C:3]=1[C:4]([NH2:6])=[O:5]

Participants

6

Reactant 2

HCID 14797Potassium HydroxideHCID 59442122HCID 59442122, compound

Product 1

HCID 178456216HCID 178456216, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 312751,4-DioxaneSolvent

Procedure

2,4-difluoro-6-({2-{[2-(methyloxy)-4-(1-propyl-4-piperidinyl)phenyl]amino}-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)benzamide (9.5 g, 13.7 mmol) was dissolved in tetrahydrofuran (100 mL) and dioxane (400 mL). A solution of KOH (35 g) in water (100 mL) was added to the reaction mixture. The mixture was heated to reflux overnight, and cooled. The organic layer was separated, dried over sodium sulfate, filtered, and adsorbed over silica. Purification by flash silica gel chromatography with a gradient from 10 to 100% of a 20:20:2:58 mixture of THF/MeOH/NH4OH/DCM in DCM provided the required product which was contaminated with ˜15% p-toluene sulfonic acid. The residue was dissolved in THF (˜400 mL) and refluxed to dissolve most of the solid. The mixture was cooled and then washed with 2 N aqueous NaOH. The separated clear organic layer was dried over sodium sulfate, filtered and concentrated. The solid obtained was recrystallized with 20% MeOH in DCM to obtain 2,4-difluoro-6-[(2-{[2-(methyloxy)-4-(1-propyl-4-piperidinyl)phenyl]amino}-1H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]benzamide (5.8 g, 79%). 1H NMR (400 MHz, DMSO-d6) δ ppm 0.85 (t, J=7.4 Hz, 3H), 1.40-1.50 (m, 2H), 1.60-1.78 (m, 4H), 1.89-1.98 (m, 2H), 2.20-2.27 (m, 2H), 2.37-2.46 (m, 1H), 2.91-2.98 (m, 2H), 3.83 (s, 3H), 6.22 (dd, J=3.4, 1.9 Hz, 1H), 6.77 (dd, J=8.3, 1.6 Hz, 1H), 6.89 (d, J=1.6 Hz, 1H), 6.93 (ddd, J=11.4, 9.0, 2.6 Hz, 1H), 7.00 (dd, J=3.5, 2.2 Hz, 1H), 7.65 (s, 1H), 7.98 (d, J=8.1 Hz, 1H), 8.03 (br. s., 1H), 8.17 (s, 1H), 8.53 (d, J=11.4 Hz, 1H), 11.08 (s, 1H), 11.42 (s, 1H); ESIMS (M+H)+=536.

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux overnight
  3. temperaturecooled
  4. customThe organic layer was separated
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. customPurification by flash silica gel chromatography with a gradient
  8. additionfrom 10 to 100% of a 20:20:2:58 mixture of THF/MeOH/NH4OH/DCM in DCM

Sources & evidence

ORD record
ord-657283b781b744d583141d717f05b651
Source dataset
uspto-grants-2011_07
Patent number
US07981903B2

Reaction notes

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