Propylamine → HCID 178457719, compound

HRID 1014486Notes

Reaction equation

HRID 1014486 reaction equation
CN(C)CC(N1C2C(=CC(OC)=C(NC3N4C(=NC5C(C4=O)=C(F)C=CC=5)C4C=CN(S(C5C=CC(C)=CC=5)(=O)=O)C=4N=3)C=2)CC1)=O.C(N)CC.[CH3:52][N:53]([CH3:102])[CH2:54][C:55]([N:57]1[C:65]2[C:60](=[CH:61][C:62]([O:100][CH3:101])=[C:63]([NH:66][C:67]3[N:68]=[C:69]([NH:86][C:87]4[CH:98]=[CH:97][CH:96]=[C:95]([F:99])[C:88]=4[C:89]([NH:91][CH2:92][CH2:93][CH3:94])=[O:90])[C:70]4[CH:75]=[CH:74][N:73](S(C5C=CC(C)=CC=5)(=O)=O)[C:71]=4[N:72]=3)[CH:64]=2)[CH2:59][CH2:58]1)=[O:56].[OH-].[Na+]>C1COCC1.C(OCC)(=O)C.O1CCOCC1>[CH3:102][N:53]([CH3:52])[CH2:54][C:55]([N:57]1[C:65]2[C:60](=[CH:61][C:62]([O:100][CH3:101])=[C:63]([NH:66][C:67]3[NH:72][C:71]4=[N:73][CH:74]=[CH:75][C:70]4=[C:69]([NH:86][C:87]4[CH:98]=[CH:97][CH:96]=[C:95]([F:99])[C:88]=4[C:89]([NH:91][CH2:92][CH2:93][CH3:94])=[O:90])[N:68]=3)[CH:64]=2)[CH2:59][CH2:58]1)=[O:56]

Participants

8

Reactant 4

HCID 7852PropylamineHCID 14798Sodium HydroxideHCID 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)-oneHCID 673175052-({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-propylbenzamide

Product 1

HCID 178457719HCID 178457719, compound

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent2×HCID 312751,4-DioxaneSolvent

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 propylamine (0.125 mL, 1.52 mmol). The resulting mixture was let stir at rt for 3 h at which time it 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. The residue was attempted to be purified via chromatography on SiO2 and afforded a solid containing 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-propylbenzamide. 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 solution of 2M NaOH, 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-propylbenzamide (68 mg, 0.121 mmol) as a beige solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 0.86 (t, J=7.38 Hz, 3 H), 1.44-1.57 (m, 2H), 2.26 (s, 6 H), 3.06-3.28 (m, 6 H), 3.18 (s, 2 H), 3.77 (s, 3 H), 4.18 (t, J=8.34 Hz, 2 H), 6.25 (dd, J=3.25, 1.79 Hz, 1 H), 6.84-7.00 (m, 3 H), 7.25-7.38 (m, 1 H), 7.57 (s, 1 H), 8.32 (d, J=8.25 Hz, 1 H), 8.55-8.67 (m, 2 H), 9.86 (s, 1 H), 11.26 (s, 1 H). (ESIMS (M+H)+=561)

Workup

  1. washwashed with a saturated sodium bicarbonate solution, water
  2. dry with materialOrganics were dried over sodium sulfate and solvents
  3. customremoved under reduced pressure
  4. customto be purified via chromatography on SiO2
  5. customafforded a solid
  6. customtransferred to a 20 ml microwave vessel
  7. customreaction
  8. temperatureheated in microwave at 120° C. for 8 minutes
  9. customResulting brown solution
  10. washwashed with a solution of 2M NaOH
  11. dry with materialOrganics were dried over sodium sulfate and solvents
  12. customremoved under reduced pressure
  13. customto afford a brown solid which
  14. customwas purified via chromatography on SiO2

Sources & evidence

ORD record
ord-699e9a385bf04b63b84501d2546df0a1
Source dataset
uspto-grants-2011_07
Patent number
US07981903B2

Reaction notes

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