Propylamine → HCID 178457720, compound

HRID 1014482Notes

Reaction equation

HRID 1014482 reaction equation
CN(C)CC(N1C2C(=CC(OC)=C(NC3N4C(=NC5C(C4=O)=C(F)C=C(F)C=5)C4C=CN(S(C5C=CC(C)=CC=5)(=O)=O)C=4N=3)C=2)CC1)=O.C(N)CC.[CH3:53][N:54]([CH3:104])[CH2:55][C:56]([N:58]1[C:66]2[C:61](=[CH:62][C:63]([O:102][CH3:103])=[C:64]([NH:67][C:68]3[N:69]=[C:70]([NH:87][C:88]4[CH:99]=[C:98]([F:100])[CH:97]=[C:96]([F:101])[C:89]=4[C:90]([NH:92][CH2:93][CH2:94][CH3:95])=[O:91])[C:71]4[CH:76]=[CH:75][N:74](S(C5C=CC(C)=CC=5)(=O)=O)[C:72]=4[N:73]=3)[CH:65]=2)[CH2:60][CH2:59]1)=[O:57].[OH-].[Na+]>C1COCC1.C(OCC)(=O)C.O1CCOCC1>[CH3:104][N:54]([CH3:53])[CH2:55][C:56]([N:58]1[C:66]2[C:61](=[CH:62][C:63]([O:102][CH3:103])=[C:64]([NH:67][C:68]3[NH:73][C:72]4=[N:74][CH:75]=[CH:76][C:71]4=[C:70]([NH:87][C:88]4[CH:99]=[C:98]([F:100])[CH:97]=[C:96]([F:101])[C:89]=4[C:90]([NH:92][CH2:93][CH2:94][CH3:95])=[O:91])[N:69]=3)[CH:65]=2)[CH2:60][CH2:59]1)=[O:57]

Participants

8

Reactant 4

HCID 7852PropylamineHCID 14798Sodium HydroxideHCID 67316372HCID 67316372, compoundHCID 673166665-{[1-(N,N-dimethylglycyl)-5-(methyloxy)-2,3-dihydro-1H-indol-6-yl]amino}-8,10-difluoro-3-[(4-methylphenyl)sulfonyl]pyrrolo[2',3':4,5]pyrimido[6,1-b]quinazolin-7(3H)-one

Product 1

HCID 178457720HCID 178457720, 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}-8,10-difluoro-3-[(4-methylphenyl)sulfonyl]pyrrolo[2′,3′:4,5]pyrimido[6,1-b]quinazolin-7(3H)-one (300 mg, 0.445 mmol) in THF (5 mL) was added propylamine (0.183 mL, 2.22 mmol). The resulting mixture was let stir at rt for 5 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 to afford a yellow 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)-4,6-difluoro-N-propylbenzamide. This crude material was dissolved in 1,4-dioxane (5 mL) and transferred to a 20 ml microwave vessel. A solution of 2 M 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 yellow 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]-4,6-difluoro-N-propylbenzamide (54 mg, 0.093 mmol) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 0.85 (t, J=7.37 Hz, 3 H) 1.41-1.56 (m, 2 H) 2.19 (s, 6 H) 3.02-3.15 (m, 4 H) 3.19-3.25 (m, 2 H) 3.72 (s, 3H) 4.11 (t, J=8.29 Hz, 2 H) 6.17 (d, J=1.28 Hz, 1 H) 6.76-6.87 (m, 1 H) 6.88-6.97 (m, 2 H) 7.74 (s, 1 H) 8.34-8.43 (m, 1 H) 8.45 (s, 1 H) 8.61 (br. s., 1 H) 10.40 (s, 1 H) 11.28 (br. s., 1 H). (ESIMS (M+H)+=579)

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

Sources & evidence

ORD record
ord-172e3eda26af41c487c11bec874d5fcc
Source dataset
uspto-grants-2011_07
Patent number
US07981903B2

Reaction notes

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