Potassium Hydroxide → HCID 178493016, compound

HRID 1014517Notes

Reaction equation

HRID 1014517 reaction equation
[CH3:1][CH:2]([N:4]1[CH2:9][CH2:8][N:7]([C:10]2[CH:15]=[CH:14][C:13]([NH:16][C:17]3[N:18]=[C:19]([NH:36][C:37]4[CH:38]=[CH:39][CH:40]=[C:41]5[C:45]=4[C:44](=[O:46])[NH:43][CH2:42]5)[C:20]4[CH:25]=[CH:24][N:23](S(C5C=CC(C)=CC=5)(=O)=O)[C:21]=4[N:22]=3)=[C:12]([O:47][CH3:48])[CH:11]=2)[CH2:6][CH2:5]1)[CH3:3].[OH-].[K+]>O1CCOCC1>[CH3:3][CH:2]([N:4]1[CH2:5][CH2:6][N:7]([C:10]2[CH:15]=[CH:14][C:13]([NH:16][C:17]3[NH:22][C:21]4=[N:23][CH:24]=[CH:25][C:20]4=[C:19]([NH:36][C:37]4[CH:38]=[CH:39][CH:40]=[C:41]5[C:45]=4[C:44](=[O:46])[NH:43][CH2:42]5)[N:18]=3)=[C:12]([O:47][CH3:48])[CH:11]=2)[CH2:8][CH2:9]1)[CH3:1]

Participants

4

Reactant 2

HCID 14797Potassium HydroxideHCID 59441626HCID 59441626, compound

Product 1

HCID 178493016HCID 178493016, compoundYield 75%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of 7-({2-{[4-[4-(1-methylethyl)-1-piperazinyl]-2-(methyloxy)phenyl]amino}-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)-2,3-dihydro-1H-isoindol-1-one (140 mg, 0.210 mmol) in 1,4-dioxane (8 mL) was added 1.0M potassium hydroxide (6.30 mL, 6.30 mmol) and the resulting reaction was heated in a microwave reactor at 120° C. for 20 min. The reaction was washed with brine (5 ml), organic layer diluted with ethyl acetate (10 mL), adsorded onto silica gel and purified by silica gel chromatography (DCM to 10% MeOH/DCM) to produce 7-[(2-{[4-[4-(1-methylethyl)-1-piperazinyl]-2-(methyloxy)phenyl]amino}-1H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]-2,3-dihydro-1H-isoindol-1-one (0.070 g, 75%). ESIMS (M+H)+=513. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.02 (d, J=6.42 Hz, 6 H) 2.61 (d, J=9.23 Hz, 4 H) 3.08-3.16 (m, 4 H) 3.81 (s, 3 H) 4.39 (s, 2 H) 6.27 (dd, J=3.41, 1.81 Hz, 1 H) 6.51 (dd, J=8.73, 2.51 Hz, 1 H) 6.64 (d, J=2.61 Hz, 1 H) 6.97 (dd, J=3.41, 2.21 Hz, 1 H) 7.10 (d, J=7.62 Hz, 1 H) 7.43-7.50 (m, 1 H) 7.53 (s, 1 H) 7.83 (d, J=8.83 Hz, 1 H) 8.69 (d, J=8.23 Hz, 2 H) 8.79 (s, 1 H) 10.45 (s, 1 H) 11.33 (s, 1 H).

Workup

  1. customthe resulting reaction
  2. washThe reaction was washed with brine (5 ml), organic layer
  3. additiondiluted with ethyl acetate (10 mL)
  4. custompurified by silica gel chromatography (DCM to 10% MeOH/DCM)

Sources & evidence

ORD record
ord-f11c981ea4ad4957b7170ad7a8ca0c5c
Source dataset
uspto-grants-2011_07
Patent number
US07981903B2

Reaction notes

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