Isopropylamine → HCID 178486488, compound

HRID 1014483Notes

Reaction equation

HRID 1014483 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)C.[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][CH:93]([CH3:95])[CH3:94])=[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][CH:93]([CH3:95])[CH3:94])=[O:91])[N:69]=3)[CH:65]=2)[CH2:60][CH2:59]1)=[O:57]

Participants

8

Reactant 4

HCID 6363IsopropylamineHCID 14798Sodium HydroxideHCID 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 673167002-({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-(1-methylethyl)benzamide

Product 1

HCID 178486488HCID 178486488, 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 (1-methylethyl)amine (0.757 mL, 8.89 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, 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-(1-methylethyl)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-(1-methylethyl)benzamide (26 mg, 0.045 mmol) as a beige solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.15 (d, J=6.60 Hz, 6H), 2.23 (s, 6 H), 3.07-3.19 (m, 4 H), 3.76 (s, 3 H), 4.07-4.22 (m, 3 H), 6.18-6.26 (m, 1 H), 6.80-6.91 (m, 1 H), 6.93-7.02 (m, 2 H), 7.79 (s, 1 H), 8.36-8.45 (m, 1 H), 8.46-8.56 (m, 2 H), 10.26 (s, 1 H), 11.28-11.37 (s, 1 H). (ESIMS (M+H)+=579)

Workup

  1. washwashed with a saturated ammonium chloride solution, 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-712c6d91ff204575ace15784fe5666af
Source dataset
uspto-grants-2011_07
Patent number
US07981903B2

Reaction notes

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