Methylamine → HCID 178485539, compound

HRID 1014533Notes

Reaction equation

HRID 1014533 reaction equation
[F:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[C:4](=[O:46])[N:5]1[C:15]([NH:16][C:17]3[CH:18]=[C:19]([N:25]([CH3:32])[C:26](=[O:31])[CH2:27][N:28]([CH3:30])[CH3:29])[CH:20]=[CH:21][C:22]=3OC)=[N:14][C:13]3[N:33](S(C4C=CC(C)=CC=4)(=O)=O)[CH:34]=[CH:35][C:12]=3[C:6]1=[N:7]2.[CH3:47][NH2:48].[OH-].[Na+].[C:51](=[O:54])(O)[O-].[Na+]>O1CCCC1.O1CCOCC1.C(OCC)(=O)C>[CH3:29][N:28]([CH3:30])[CH2:27][C:26]([N:25]([CH3:32])[C:19]1[CH:20]=[CH:21][C:22]([O:54][CH3:51])=[C:17]([NH:16][C:15]2[NH:14][C:13]3=[N:33][CH:34]=[CH:35][C:12]3=[C:6]([NH:7][C:8]3[CH:9]=[CH:10][CH:11]=[C:2]([F:1])[C:3]=3[C:4]([NH:48][CH3:47])=[O:46])[N:5]=2)[CH:18]=1)=[O:31]

Participants

8

Reactant 4

HCID 6329MethylamineHCID 14798Sodium HydroxideHCID 516892Sodium BicarbonateHCID 67316278N1-[3-({8-fluoro-3-[(4-methylphenyl)sulfonyl]-7-oxo-3,7-dihydropyrrolo[2',3':4,5]pyrimido[6,1-b]quinazolin-5-yl}amino)-4-(methyloxy)phenyl]-N1,N2,N2-trimethylglycinamide

Product 1

HCID 178485539HCID 178485539, compoundYield 21.64%

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of N1-[3-({8-fluoro-3-[(4-methylphenyl)sulfonyl]-7-oxo-3,7-dihydropyrrolo[2′,3′:4,5]pyrimido[6,1-b]quinazolin-5-yl}amino)-4-(methyloxy)phenyl]-N1,N2,N2-trimethylglycinamide (0.800 g, 1.243 mmol) in tetrahydrofuran (75 ml) was treated with 2.0M methyl amine (3.11 ml, 6.21 mmol) and maintained at room temperature overnight. The reaction was taken to a residue under reduced pressure, dissolved in 1,4-dioxane (8 ml), and added to a microwave vial along with 2.0N NaOH (aq) (8 ml). The mixture was maintained under microwave heating at 120° C. for 12 minutes, cooled, and poured into saturated sodium bicarbonate and ethyl acetate. The organic layer was separated, dried over sodium sulfate, filtered, stripped onto celite, and purified by column chromatography to afford 2-[(2-{[5-[(N,N-dimethylglycyl)(methyl)amino]-2-(methyloxy)phenyl]amino}-1H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]-6-fluoro-N-methylbenzamide (0.140 g, 0.269 mmol, 21.64% yield) as a pale yellow solid. 1H NMR (400 MHz, DMSO-d6) 6 ppm 11.47 (br. s., 1 H), 10.05 (s, 1 H), 8.54 (d, J=3.8 Hz, 1 H), 8.44 (br. s., 1 H), 8.14 (d, J=8.2 Hz, 7.59 (s, 1 H), 7.36-7.50 (m, 1 H), 6.93-7.06 (m, 3 H), 6.84 (br. s., 1 H), 6.35 (br.s., 1 H), 3.91 (s, 3 H), 3.11 (s, 3 H), 2.86 (s, 2 H), 2.77 (d, J=4.4 Hz, 3 H), 2.11 (s, 6 H). ESIMS (M+H)+=521.

Workup

  1. temperatureThe mixture was maintained under microwave
  2. temperatureheating at 120° C. for 12 minutes
  3. temperaturecooled
  4. customThe organic layer was separated
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. custompurified by column chromatography

Sources & evidence

ORD record
ord-b9a09331d5834978a892a9168eba6afb
Source dataset
uspto-grants-2011_07
Patent number
US07981903B2

Reaction notes

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