Ethylamine → HCID 178464913, compound

HRID 1014481Notes

Reaction equation

HRID 1014481 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)C.[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:97]=[C:96]([F:98])[CH:95]=[C:94]([F:99])[C:88]=4[C:89]([NH:91][CH2:92][CH3:93])=[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:97]=[C:96]([F:98])[CH:95]=[C:94]([F:99])[C:88]=4[C:89]([NH:91][CH2:92][CH3:93])=[O:90])[N:68]=3)[CH:64]=2)[CH2:59][CH2:58]1)=[O:56]

Participants

8

Reactant 4

HCID 6341EthylamineHCID 14798Sodium HydroxideHCID 673163292-({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-ethyl-4,6-difluorobenzamideHCID 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 178464913HCID 178464913, compound

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolvent2×HCID 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 ethyl amine as a 2M solution in THF (1.11 mL, 2.22 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 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)-N-ethyl-4,6-difluorobenzamide. This 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 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]-N-ethyl-4,6-difluorobenzamide (60 mg, 0.101 mmol) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.14 (t, J=7.14 Hz, 3 H) 2.18-2.31 (m, 6 H) 3.06-3.19 (m, 4H) 3.34 (dq, J=6.87, 6.65 Hz, 2 H) 3.78 (s, 3 H) 4.09-4.24 (m, 2 H) 6.25 (br. s., 1 H) 6.75-6.89 (m, 1 H) 6.93-7.03 (m, 2 H) 7.62-7.75 (m, 1 H) 8.39-8.49 (m, 1 H) 8.55 (br. s., 2 H) 10.55 (s, 1H) 11.26 (dd, J=2.56, 1.10 Hz, 1 H) (ESIMS (M+H)+=565)

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-5deb3479d3214a43be1c38a0fe6051f0
Source dataset
uspto-grants-2011_07
Patent number
US07981903B2

Reaction notes

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