Potassium Hydroxide → HCID 178485517, compound

HRID 1014542Notes

Reaction equation

HRID 1014542 reaction equation
[CH3:1][N:2]([CH3:49])[CH2:3][C:4]([N:6]1[C:15]2[C:10](=[CH:11][C:12]([CH3:48])=[C:13]([NH:16][C:17]3[N:18]=[C:19]([NH:36][C:37]4[CH:46]=[CH:45][CH:44]=[C:43]([F:47])[C:38]=4[C:39]([NH:41][CH3:42])=[O:40])[C:20]4[CH:25]=[CH:24][N:23](S(C5C=CC(C)=CC=5)(=O)=O)[C:21]=4[N:22]=3)[CH:14]=2)[CH2:9][CH2:8][CH2:7]1)=[O:5].[OH-].[K+].C([O-])(O)=O.[Na+]>O1CCOCC1.CCOC(C)=O>[CH3:49][N:2]([CH3:1])[CH2:3][C:4]([N:6]1[C:15]2[C:10](=[CH:11][C:12]([CH3:48])=[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:46]=[CH:45][CH:44]=[C:43]([F:47])[C:38]=4[C:39]([NH:41][CH3:42])=[O:40])[N:18]=3)[CH:14]=2)[CH2:9][CH2:8][CH2:7]1)=[O:5]

Participants

6

Reactant 3

HCID 14797Potassium HydroxideHCID 516892Sodium BicarbonateHCID 59441868HCID 59441868, compound

Product 1

HCID 178485517HCID 178485517, compoundYield 61%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

A mixture of 2-({2-{[1-(N,N-dimethylglycyl)-6-methyl-1,2,3,4-tetrahydro-7-quinolinyl]amino}-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)-6-fluoro-N-methylbenzamide (87 mg, 0.127 mmol) and a 1M aqueous KOH solution (1.270 mL, 1.270 mmol) in dioxane (50 mL) was heated at 80° C. for 10 h. The resulting mixture was allowed to cool to rt, diluted with EtOAc (100 mL) and a saturated NaHCO3 solution. The organic layer was washed with a saturated NaCl solution (100 mL), concentrated onto Celite and purified by silica gel chromatography (ISCO 12 g) using 1-10% MeOH (containing 0.2% NH3)/CH2Cl2. The product was taken up into a mixture of CH2Cl2 and Et2O and concentrated again to afford 2-[(2-{[1-(N,N-dimethylglycyl)-6-methyl-1,2,3,4-tetrahydro-7-quinolinyl]amino}-1H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]-6-fluoro-N-methylbenzamide as a pale yellow solid (41 mg, 61%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.79-1.96 (m, 2H), 2.12 (s, 6H), 2.16 (s, 3H), 2.69 (t, J=6.41 Hz, 2H), 2.81 (d, J=4.58 Hz, 3H), 3.18 (br s, 2H), 3.71 (t, J=5.86 Hz, 2H), 6.23 (d, J=1.47 Hz, 1H), 6.82-6.96 (m, 2H), 7.00 (s, 1H), 7.16-7.34 (m, 1H), 7.79 (br s, 1H), 8.04 (s, 1H), 8.34 (d, J=8.42 Hz, 1H), 8.44-8.61 Hz, 1H), 10.16 (s, 1H), 11.22 (br s, 1H); ESIMS (M+H)+=531.17.

Workup

  1. washThe organic layer was washed with a saturated NaCl solution (100 mL)
  2. concentrationconcentrated onto Celite
  3. custompurified by silica gel chromatography (ISCO 12 g)
  4. additionThe product was taken up into a mixture of CH2Cl2 and Et2O
  5. concentrationconcentrated again

Sources & evidence

ORD record
ord-ca3cef9fc7384865b6e931b73ace9ec4
Source dataset
uspto-grants-2011_07
Patent number
US07981903B2

Reaction notes

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