Isopropylamine → HCID 178486484, compound

HRID 1014502Notes

Reaction equation

HRID 1014502 reaction equation
CN(C)CC(N1C2C(=CC(OC)=C(NC3N4C(=NC5C(C4=O)=C(F)C(F)=CC=5)C4C=CN(S(C5C=CC(C)=CC=5)(=O)=O)C=4N=3)C=2)CCC1)=O.CC(N)C.[CH3:54][N:55]([CH3:106])[CH2:56][C:57]([N:59]1[C:68]2[C:63](=[CH:64][C:65]([O:104][CH3:105])=[C:66]([NH:69][C:70]3[N:71]=[C:72]([NH:89][C:90]4[C:95]([C:96]([NH:98][CH:99]([CH3:101])[CH3:100])=[O:97])=[C:94]([F:102])[C:93]([F:103])=[CH:92][CH:91]=4)[C:73]4[CH:78]=[CH:77][N:76](S(C5C=CC(C)=CC=5)(=O)=O)[C:74]=4[N:75]=3)[CH:67]=2)[CH2:62][CH2:61][CH2:60]1)=[O:58].[OH-].[Na+]>C1COCC1.C(OCC)(=O)C.O1CCOCC1.O>[CH3:106][N:55]([CH3:54])[CH2:56][C:57]([N:59]1[C:68]2[C:63](=[CH:64][C:65]([O:104][CH3:105])=[C:66]([NH:69][C:70]3[NH:75][C:74]4=[N:76][CH:77]=[CH:78][C:73]4=[C:72]([NH:89][C:90]4[C:95]([C:96]([NH:98][CH:99]([CH3:101])[CH3:100])=[O:97])=[C:94]([F:102])[C:93]([F:103])=[CH:92][CH:91]=4)[N:71]=3)[CH:67]=2)[CH2:62][CH2:61][CH2:60]1)=[O:58]

Participants

9

Reactant 4

HCID 6363IsopropylamineHCID 14798Sodium HydroxideHCID 67315992HCID 67315992, compoundHCID 67317076HCID 67317076, compound

Product 1

HCID 178486484HCID 178486484, compound

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent2×HCID 312751,4-DioxaneSolvent

Procedure

To a solution of 5-{[1-(N,N-dimethylglycyl)-6-(methyloxy)-1,2,3,4-tetrahydro-7-quinolinyl]amino}-8,9-difluoro-3-[(4-methylphenyl)sulfonyl]pyrrolo[2′,3′:4,5]pyrimido[6,1-b]quinazolin-7(3H)-one (300 mg, 0.436 mmol) in THF (5 mL) was added (1-methylethyl)amine (1.4 mL, 17.44 mmol). The resulting mixture was let stir at rt for 2 h at which time it was diluted with ethyl acetate and washed with 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 yellow solid containing about 50% 6-({2-{[1-(N,N-dimethylglycyl)-6-(methyloxy)-1,2,3,4-tetrahydro-7-quinolinyl]amino}-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)-2,3-difluoro-N-(1-methylethyl)benzamide mmol) as a yellow solid. This crude material was dissolved in 1,4-dioxane (6 mL) and transferred to a 20 ml microwave vessel. Water (2 mL) and a solution of 6M NaOH (2 ml) was added and reaction mixture heated in microwave at 120° C. for 10 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 brown solid that was purified via chromatography on SiO2 to afford 6-[(2-{[1-(N,N-dimethylglycyl)-6-(methyloxy)-1,2,3,4-tetrahydro-7-quinolinyl]amino}-1H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]-2,3-difluoro-N-(1-methylethyl)benzamide (42 mg, 0.071 mmol) as an off white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.00 (d, J=6.59 Hz, 6 H) 1.81-1.92 (m, 2 H) 2.12 (br. s., 6 H) 2.60-2.73 (m, 2 H) 3.24 (s, 2 H) 3.69 (t, J=6.04 Hz, 2 H) 3.83 (s, 3 H) 3.90-4.03 (m, 1 H) 6.34 (d, J=0.92 Hz, 1 H) 6.81 (br. s., 1 H) 6.91-6.99 (m, 1 H) 7.38-7.51 (m, 2 H) 7.74-7.87 (m, 1 H) 8.41 (d, J=7.69 Hz, 2 H), 9.29 (s, 1 H) 11.30 (br. s., 1 H) (ESIMS (M+H)+=593)

Workup

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

Sources & evidence

ORD record
ord-889cf11c401542b585eefd369cadcac6
Source dataset
uspto-grants-2011_07
Patent number
US07981903B2

Reaction notes

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