Sodium Hydroxide → HCID 178464229, compound

HRID 1014460Notes

Reaction equation

HRID 1014460 reaction equation
[CH2:1]([N:3]([CH3:51])[CH2:4][C:5]([N:7]1[C:16]2[C:11](=[CH:12][C:13]([O:49][CH3:50])=[C:14]([NH:17][C:18]3[N:19]=[C:20]([NH:37][C:38]4[CH:47]=[CH:46][CH:45]=[C:44]([F:48])[C:39]=4[C:40]([NH:42][CH3:43])=[O:41])[C:21]4[CH:26]=[CH:25][N:24](S(C5C=CC(C)=CC=5)(=O)=O)[C:22]=4[N:23]=3)[CH:15]=2)[CH2:10][CH2:9][CH2:8]1)=[O:6])[CH3:2].[OH-].[Na+].C(OCC)(=O)C.C1COCC1>O1CCOCC1>[CH2:1]([N:3]([CH3:51])[CH2:4][C:5]([N:7]1[C:16]2[C:11](=[CH:12][C:13]([O:49][CH3:50])=[C:14]([NH:17][C:18]3[NH:23][C:22]4=[N:24][CH:25]=[CH:26][C:21]4=[C:20]([NH:37][C:38]4[CH:47]=[CH:46][CH:45]=[C:44]([F:48])[C:39]=4[C:40]([NH:42][CH3:43])=[O:41])[N:19]=3)[CH:15]=2)[CH2:10][CH2:9][CH2:8]1)=[O:6])[CH3:2]

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 21939870Tetrahydrofuran ethyl acetateHCID 67316391HCID 67316391, compound

Product 1

HCID 178464229HCID 178464229, compoundYield 35%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

A solution of 5-chloro-8-fluoro-3-[(4-methylphenyl)sulfonyl]pyrrolo[2′,3′:4,5]pyrimido[6,1-b]quinazolin-7(3H)-one hydrogen chloride (500 mg, 1.043 mmol) and 1-{[ethyl(methyl)amino]acetyl}-6-(methyloxy)-1,2,3,4-tetrahydro-7-quinolinamine (289 mg, 1.043 mmol) in 2,2,2-trifluoroethanol (10 ml) was warmed to 90° C. in a pressure flask and maintained for 3 hours. The vial was cooled and its contents poured into saturated sodium bicarbonate/methylene chloride. The organic layer was dried over sodium sulfate, filtered, and taken to a residue under reduced pressure. The residue was triturated with diethyl ether to afford a yellow solid (ca 310 mg). The solid was suspended in tetrahydrofuran (100 ml) and 2.0M methyl amine in THF (5.22 ml, 10.43 mmol) was added. The solution was stirred for 16 hours and concentrated to a solid under reduced pressure to afford 2-({2-{[1-(N-ethyl-N-methylglycyl)-6-(methyloxy)-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 (310 mg, 0.434 mmol, 41.6%) as a yellow solid. A solution of 2-({2-{[1-(N-ethyl-N-methylglycyl)-6-(methyloxy)-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 (310 mg, 0.434 mmol) in 1,4-dioxane (8.00 ml) was added to a microwave vial along with 2.0N NaOH (aq) (8 ml). The vial was sealed and contents warmed at 120° C. for 12 minutes. The reaction was cooled, opened, and poured into ethyl acetate/THF/saturated sodium chloride. The organic layer was dried over sodium sulfate, filtered, stripped onto celite, and purified by column chromatography to afford 2-[(2-{[1-(N-ethyl-N-methylglycyl)-6-(methyloxy)-1,2,3,4-tetrahydro-7-quinolinyl]amino}-1H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]-6-fluoro-N-methylbenzamide (0.085 g, 0.152 mmol, 35.0%) as a pale violet solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.34 (s, 1H), 10.06 (s, 1H), 8.49 (d, J=4.21 Hz, 1H), 8.38 (s, 1H), 8.20 (d, J=8.24 Hz, 1H), 7.45 (s, 1H), 7.27-7.39 (m, 1H), 6.86-6.99 (m, 2H), 6.78 (s, 1H), 6.26 (s, 1H), 3.80 (s, 3H), 3.66 (t, J=5.31 Hz, 2H), 3.27 (s, 2H), 2.74 (d, J=4.39 Hz, 3H), 2.62 (s, 2H), 2.28 (s, 2H), 2.06 (s, 3H), 1.71-1.89 (m, 2H), 0.74 (s, 3H). ESIMS (M+H)+=561.

Workup

  1. customThe vial was sealed
  2. temperatureThe reaction was cooled
  3. dry with materialThe organic layer was dried over sodium sulfate
  4. filtrationfiltered
  5. custompurified by column chromatography

Sources & evidence

ORD record
ord-06ca6bd0f4ea4a3d96cf47ded64b851f
Source dataset
uspto-grants-2011_07
Patent number
US07981903B2

Reaction notes

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