Water → HCID 178485548, compound

HRID 1014501Notes

Reaction equation

HRID 1014501 reaction equation
[CH3:1][N:2]([CH3:51])[CH2:3][C:4]([N:6]1[C:15]2[C:10](=[CH:11][C:12]([O:49][CH3:50])=[C:13]([NH:16][C:17]3[N:18]=[C:19]([NH:36][C:37]4[C:42]([C:43]([NH:45][CH3:46])=[O:44])=[C:41]([F:47])[C:40]([F:48])=[CH:39][CH:38]=4)[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].O.[OH-].[Na+]>O1CCOCC1.C(OCC)(=O)C>[CH3:51][N:2]([CH3:1])[CH2:3][C:4]([N:6]1[C:15]2[C:10](=[CH:11][C:12]([O:49][CH3:50])=[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[C:42]([C:43]([NH:45][CH3:46])=[O:44])=[C:41]([F:47])[C:40]([F:48])=[CH:39][CH:38]=4)[N:18]=3)[CH:14]=2)[CH2:9][CH2:8][CH2:7]1)=[O:5]

Participants

6

Reactant 3

HCID 962WaterHCID 14798Sodium HydroxideHCID 67316507HCID 67316507, compound

Product 1

HCID 178485548HCID 178485548, compoundYield 46.6%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

6-({2-{[1-(N,N-dimethylglycyl)-6-(methyloxy)-1,2,3,4-tetrahydro-7-quinolinyl]amino}-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)-2,3-difluoro-N-methylbenzamide (139 mg, 0.193 mmol) was dissolved in 1,4-dioxane (6 mL) and transferred to a 20 ml microwave vessel. Water (2 mL) and a solution of 6M NaOH (2 ml) and was added and reaction heated in microwave at 120° C. for 10 minutes. Resulting brown solution was diluted with ethyl acetate and washed with a saturated sodium bicarbonate solution, water and a saturated brine solution. Organics were dried over sodium sulfate and solvents removed under reduced pressure to afford a brown solid that was purified via chromatography on SiO2 to afford 6-[(2-{[1-(N,N-dimethylglycyl)-6-(methyloxy)-1,2,3,4-tetrahydro-7-quinolinyl]amino}-1H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]-2,3-difluoro-N-methylbenzamide (51 mg, 0.090 mmol) as a tan solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.81-1.92 (m, 2 H), 2.11 (br. s., 6H), 2.67 (br. s., 2 H), 2.74 (d, J=4.49 Hz, 3 H), 3.24 (s, 2 H), 3.69 (t, J=6.09 Hz, 2 H), 3.84 (s, 3 H), 5.76 (s, 1 H), 6.34 (d, J=1.10 Hz, 1 H), 6.82 (br. s., 1 H), 6.96 (br. s., 1 H), 7.38-7.51 (m, 2 H), 7.90-8.01 (m, 1 H), 8.38-8.48 (m, 1 H), 8.63 (d, J=4.67 Hz, 1 H), 9.58 (s, 1 H), 11.33 (br.s, 1 H). (ESIMS (M+H)+=565)

Workup

  1. customtransferred to a 20 ml microwave vessel
  2. customreaction
  3. customResulting brown solution
  4. washwashed with a saturated sodium bicarbonate solution, water
  5. dry with materialOrganics were dried over sodium sulfate and solvents
  6. customremoved under reduced pressure
  7. customto afford a brown solid that
  8. customwas purified via chromatography on SiO2

Sources & evidence

ORD record
ord-02b2581b086740edbf2d1ff2ac6d114e
Source dataset
uspto-grants-2011_07
Patent number
US07981903B2

Reaction notes

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