Sodium Hydroxide → HCID 178486489, compound

HRID 1014484Notes

Reaction equation

HRID 1014484 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.CC(N)CC.[CH3:54][N:55]([CH3:106])[CH2:56][C:57]([N:59]1[C:67]2[C:62](=[CH:63][C:64]([O:104][CH3:105])=[C:65]([NH:68][C:69]3[N:70]=[C:71]([NH:88][C:89]4[CH:101]=[C:100]([F:102])[CH:99]=[C:98]([F:103])[C:90]=4[C:91]([NH:93][CH2:94][CH:95]([CH3:97])[CH3:96])=[O:92])[C:72]4[CH:77]=[CH:76][N:75](S(C5C=CC(C)=CC=5)(=O)=O)[C:73]=4[N:74]=3)[CH:66]=2)[CH2:61][CH2:60]1)=[O:58].[OH-].[Na+]>C1COCC1.C(OCC)(=O)C.O1CCOCC1>[CH3:106][N:55]([CH3:54])[CH2:56][C:57]([N:59]1[C:67]2[C:62](=[CH:63][C:64]([O:104][CH3:105])=[C:65]([NH:68][C:69]3[NH:74][C:73]4=[N:75][CH:76]=[CH:77][C:72]4=[C:71]([NH:88][C:89]4[CH:101]=[C:100]([F:102])[CH:99]=[C:98]([F:103])[C:90]=4[C:91]([NH:93][CH2:94][CH:95]([CH3:97])[CH3:96])=[O:92])[N:70]=3)[CH:66]=2)[CH2:61][CH2:60]1)=[O:58]

Participants

8

Reactant 4

HCID 14798Sodium HydroxideHCID 24874Sec-ButylamineHCID 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)-oneHCID 673167022-({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-(2-methylpropyl)benzamide

Product 1

HCID 178486489HCID 178486489, 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 methyl-1-propanamine (0.22 mL, 2.22 mmol). The resulting mixture was let stir at rt for 6 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-(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 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-(2-methylpropyl)benzamide (50 mg, 0.084 mmol) as a beige solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 0.90 (d, J=6.69 Hz, 6 H) 1.84 (dt, J=13.40, 6.72 Hz, 1 H), 2.24 (s, 6 H), 3.07-3.20 (m, 6 H), 3.76 (s, 3H), 4.16 (t, J=8.34 Hz, 2 H), 6.21 (dd, J=3.21, 1.65 Hz, 1 H), 6.79-6.93 (m, 1 H), 6.93-7.01 (m, 2 H), 7.79 (s, 1 H), 8.39-8.47 (m, 1 H), 8.50 (s, 1 H), 8.63-8.74 (m, 1 H), 10.32 (s, 1 H), 11.32 (br. s., 1 H). (ESIMS (M+H)+=593)

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-6a1aef641e9843a3ab9a0124d2d2288a
Source dataset
uspto-grants-2011_07
Patent number
US07981903B2

Reaction notes

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