Sodium Chloride → HCID 178485231, compound

HRID 1014449Notes

Reaction equation

HRID 1014449 reaction equation
CN.[CH3:3][N:4]([CH3:54])[CH2:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([O:52][CH3:53])=[C:14]([NH:17][C:18]3[N:19]=[C:20]([NH:37][C:38]4[C:39]([C:48]([NH:50][CH3:51])=[O:49])=[CH:40][C:41]5[C:46]([CH:47]=4)=[CH:45][CH:44]=[CH:43][CH:42]=5)[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]1)=[O:7].C[O-].[Na+].[Na+].[Cl-]>O1CCCC1.CO.C1COCC1.C(OCC)(=O)C>[CH3:54][N:4]([CH3:3])[CH2:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([O:52][CH3:53])=[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[C:39]([C:48]([NH:50][CH3:51])=[O:49])=[CH:40][C:41]5[C:46]([CH:47]=4)=[CH:45][CH:44]=[CH:43][CH:42]=5)[N:19]=3)[CH:15]=2)[CH2:10][CH2:9]1)=[O:7]

Participants

8

Reactant 4

HCID 5234Sodium ChlorideHCID 6329MethylamineHCID 10942334Sodium MethoxideHCID 67317064HCID 67317064, compound

Product 1

HCID 178485231HCID 178485231, compoundYield 70.1%

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolventHCID 21899815MeOH tetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

Filtrates containing 5-{[1-(N,N-dimethylglycyl)-5-(methyloxy)-2,3-dihydro-1H-indol-6-yl]amino}-3,14-dihydro-7H-6I5-benzo[g]pyrrolo[2′,3′:4,5]pyrimido[6,1-b]quinazolin-7-one (generated above) were taken to a residue under reduced pressure, redissolved in tetrahydrofuran, and 2.0M methyl amine in tetrahydrofuran (5 mL) was added. The solution was stirred for 12 hours and all solids were evaporated under reduced pressure to generate crude 3-({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)-N-methyl-2-naphthalenecarboxamide of sufficient purity for direct use in the subsequent transformations. To a solution of 3-({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)-N-methyl-2-naphthalenecarboxamide (100 mg, 0.139 mmol) in MeOH/THF (1:1, 10 mL) was added sodium methoxide (113 mg, 2.087 mmol). The resulting solution was warmed to 80° C. for 45 minutes, cooled to room temperature, and poured into saturated aqueous NaCl (50 mL) and diluted with ethyl acetate (25 mL). The organic layer was dried over solid sodium sulfate, filtered, stripped onto celite, and purified by chromatography on SiO2 to give 3-[(2-{[1-(N,N-dimethylglycyl)-5-(methyloxy)-2,3-dihydro-1H-indol-6-yl]amino}-1H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]-N-methyl-2-naphthalenecarboxamide as a yellow solid (0.055 g); 1H NMR (400 MHz, DMSO-d6) δ ppm 11.42 (s, 1H), 11.20 (s, 1H), 9.22 (s, 1H), 8.89-9.00 (m, 1H), 8.58 (s, 1H), 8.26 (s, 1H), 7.78 (d, J=8.06 Hz, 1H), 7.66 (s, 1H), 7.46-7.54 (m, 1H), 7.40-7.46 (m, 1H), 7.34 (t, J=7.42 Hz, 1H), 6.98 (s, 1H), 6.90-6.95 (m, 1H), 6.28 (dd, J=3.02, 1.74 Hz, 1H), 4.16 (t, J=8.33 Hz, 2H), 3.74 (s, 3H), 3.16 (t, J=8.42 Hz, 2H), 2.97 (s, 2H), 2.85 (d, J=4.58 Hz, 3H), 2.00 (s, 6H). ESIMS (M+H)+=565.

Workup

  1. customall solids were evaporated under reduced pressure
  2. temperaturecooled to room temperature
  3. dry with materialThe organic layer was dried over solid sodium sulfate
  4. filtrationfiltered
  5. custompurified by chromatography on SiO2

Sources & evidence

ORD record
ord-e8becfffb41e4b3b997c4e7bbd8fa00c
Source dataset
uspto-grants-2011_07
Patent number
US07981903B2

Reaction notes

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