Water → HCID 178486480, compound

HRID 1014489Notes

Reaction equation

HRID 1014489 reaction equation
[CH3:1][N:2]([CH3:51])[CH2:3][C:4]([N:6]1[C:14]2[C:9](=[CH:10][C:11]([O:49][CH3:50])=[C:12]([NH:15][C:16]3[N:17]=[C:18]([NH:35][C:36]4[CH:47]=[CH:46][CH:45]=[C:44]([F:48])[C:37]=4[C:38]([NH:40][CH:41]([CH3:43])[CH3:42])=[O:39])[C:19]4[CH:24]=[CH:23][N:22](S(C5C=CC(C)=CC=5)(=O)=O)[C:20]=4[N:21]=3)[CH:13]=2)[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:14]2[C:9](=[CH:10][C:11]([O:49][CH3:50])=[C:12]([NH:15][C:16]3[NH:21][C:20]4=[N:22][CH:23]=[CH:24][C:19]4=[C:18]([NH:35][C:36]4[CH:47]=[CH:46][CH:45]=[C:44]([F:48])[C:37]=4[C:38]([NH:40][CH:41]([CH3:43])[CH3:42])=[O:39])[N:17]=3)[CH:13]=2)[CH2:8][CH2:7]1)=[O:5]

Participants

6

Reactant 3

HCID 962WaterHCID 14798Sodium HydroxideHCID 673159842-({2-{[1-(N,N-dimethylglycyl)-5-(methyloxy)-2,3-dihydro-1H-indol-6-yl]amino}-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)-6-fluoro-N-(1-methylethyl)benzamide

Product 1

HCID 178486480HCID 178486480, compoundYield 72.8%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

2-({2-{[1-(N,N-dimethylglycyl)-5-(methyloxy)-2,3-dihydro-1H-indol-6-yl]amino}-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)-6-fluoro-N-(1-methylethyl)benzamide (210 mg, 0.294 mmol) was dissolved in 1,4-dioxane (10 mL) and transferred to a 20 ml microwave vessel. Water (3 mL) and a solution of 6M NaOH (3 ml) 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 2-[(2-{[1-(N,N-dimethylglycyl)-5-(methyloxy)-2,3-dihydro-1H-indol-6-yl]amino}-1H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]-6-fluoro-N-(1-methylethyl)benzamide (120 mg, 0.214 mmol) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.11 (d, J=6.50 Hz, 6 H), 2.25 (s, 6 H), 3.05-3.22 (m, 4 H), 3.77 (s, 3 H), 4.03-4.13 (m, 1 H), 4.18 (t, J=8.29 Hz, 2 H), 6.26 (br. s., 1 H), 6.84-7.01 (m, 3 H), 7.25-7.38 (m, 1 H), 7.57 (s, 1 H), 8.25 (d, J=8.33 Hz, 1 H), 8.45 (d, J=7.60 Hz, 1 H), 8.64 (s, 1 H), 9.69 (s, 1 H), 11.25 (br. s., 1 H). (ESIMS (M+H)+=561)

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-0c9d3e3468044674aa6bf4934e217880
Source dataset
uspto-grants-2011_07
Patent number
US07981903B2

Reaction notes

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