Isobutylamine → 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-(2-methylpropyl)benzamide

HRID 1014487Notes

Reaction equation

HRID 1014487 reaction equation
[CH3:1][N:2]([CH3:47])[CH2:3][C:4]([N:6]1[C:14]2[C:9](=[CH:10][C:11]([O:45][CH3:46])=[C:12]([NH:15][C:16]3[N:29]4[C:20](=[N:21][C:22]5[C:27]([C:28]4=[O:30])=[C:26]([F:31])[CH:25]=[CH:24][CH:23]=5)[C:19]4[CH:32]=[CH:33][N:34]([S:35]([C:38]5[CH:43]=[CH:42][C:41]([CH3:44])=[CH:40][CH:39]=5)(=[O:37])=[O:36])[C:18]=4[N:17]=3)[CH:13]=2)[CH2:8][CH2:7]1)=[O:5].[CH3:48][CH:49]([CH3:52])[CH2:50][NH2:51]>C1COCC1.C(OCC)(=O)C>[CH3:1][N:2]([CH3:47])[CH2:3][C:4]([N:6]1[C:14]2[C:9](=[CH:10][C:11]([O:45][CH3:46])=[C:12]([NH:15][C:16]3[N:29]=[C:20]([NH:21][C:22]4[CH:23]=[CH:24][CH:25]=[C:26]([F:31])[C:27]=4[C:28]([NH:51][CH2:50][CH:49]([CH3:52])[CH3:48])=[O:30])[C:19]4[CH:32]=[CH:33][N:34]([S:35]([C:38]5[CH:43]=[CH:42][C:41]([CH3:44])=[CH:40][CH:39]=5)(=[O:37])=[O:36])[C:18]=4[N:17]=3)[CH:13]=2)[CH2:8][CH2:7]1)=[O:5]

Participants

5

Reactant 2

HCID 6558IsobutylamineHCID 673164855-{[1-(N,N-dimethylglycyl)-5-(methyloxy)-2,3-dihydro-1H-indol-6-yl]amino}-8-fluoro-3-[(4-methylphenyl)sulfonyl]pyrrolo[2',3':4,5]pyrimido[6,1-b]quinazolin-7(3H)-one

Product 1

HCID 673152512-({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-(2-methylpropyl)benzamide

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 5-{[1-(N,N-dimethylglycyl)-5-(methyloxy)-2,3-dihydro-1H-indol-6-yl]amino}-8-fluoro-3-[(4-methylphenyl)sulfonyl]pyrrolo[2′,3′:4,5]pyrimido[6,1-b]quinazolin-7(3H)-one (200 mg, 0.305 mmol) in THF (5 mL) was added (2-methylpropyl)amine (0.153 mL, 1.52 mmol). The resulting mixture was let stir at rt for 16 h at which time it was diluted with ethyl acetate and washed with a saturated ammonium chloride solution,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 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-(2-methylpropyl)benzamide. This crude material was dissolved in 1,4-dioxane (5 mL) and transferred to a 20 ml microwave vessel. A solution of 2M NaOH (5 ml) was added and reaction heated in microwave at 120° C. for 8 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 which 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-(2-methylpropyl)benzamide (106 mg, 0.184 mmol) as a pale yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 0.87 (d, J=6.68 Hz, 6 H), 1.73-1.89 (m, 1 H), 2.26 (s, 6 H), 3.05-3.23 (m, 6 H), 3.77 (s, 3 H), 4.18 (t, J=8.33 Hz, 2 H), 6.24 (br. s., 1 H), 6.83-7.00 (m, 3 H), 7.24-7.38 (m, 1 H), 7.56 (s, 1 H), 8.32 (d, J=8.42 Hz, 1 H), 8.57-8.68 (m, 2 H), 9.77 (s, 1 H), 11.26 (br. s., 1 H). (ESIMS (M+H)+=575)

Workup

  1. washwashed with a saturated ammonium chloride
  2. dry with materialOrganics were dried over sodium sulfate and solvents
  3. customremoved under reduced pressure

Sources & evidence

ORD record
ord-3c5e11dd07ea48fb9617a2960c6372b9
Source dataset
uspto-grants-2011_07
Patent number
US07981903B2

Reaction notes

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