Triethylamine → HCID 178440394, compound

HRID 1987609Notes

Reaction equation

HRID 1987609 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[NH:5]/[C:4](=[C:12]2/[C:13]([CH:18]([CH3:20])[CH3:19])=[N:14][NH:15][C:16]/2=[O:17])/[CH:3]=1.C(OC(OC(C)(C)C)=O)(OC(C)(C)C)=O.C(N(CC)CC)C.C(OC(N1C(=O)/C(=C2\N(C(OC(C)(C)C)=O)C3C(C(Cl)=C\2)=CC=CC=3)/C(C(C)C)=N1)=O)(C)(C)C.[NH2:77][C:78]1[CH:83]=[CH:82][C:81]([SH:84])=[CH:80][CH:79]=1.[CH3:85][S:86](Cl)(=[O:88])=[O:87]>CN(C=O)C.CCOC(C)=O.C(O)C.O>[CH:18]([C:13]1=[N:14][NH:15][C:16](=[O:17])/[C:12]/1=[C:4]1\[NH:5][C:6]2[C:11]([C:2]([S:84][C:81]3[CH:82]=[CH:83][C:78]([NH:77][S:86]([CH3:85])(=[O:88])=[O:87])=[CH:79][CH:80]=3)=[CH:3]\1)=[CH:10][CH:9]=[CH:8][CH:7]=2)([CH3:20])[CH3:19]

Participants

11

Reactant 6

HCID 8471TriethylamineHCID 145104-AminothiophenolHCID 31297Methanesulfonyl chlorideHCID 90495Di-tert-butyl dicarbonateHCID 69053817(Z)-tert-butyl 2-(1-(tert-butoxycarbonyl)-3-isopropyl-5-oxo-1H-pyrazol-4(5H)-ylidene)-4-chloroquinoline-1(2H)-carboxylateHCID 178440351HCID 178440351, compound

Product 1

HCID 178440394HCID 178440394, compound

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
30 °C

Procedure

(Z)-4-(4-chloroquinolin-2(1H)-ylidene)-3-isopropyl-1H-pyrazol-5(4H)-one (0.8 g, 2.78 mmol) was stirred in DMF at ambient temperature and Di-t-butyl dicarbonate (3 g, 13.9 mmol) was added followed by triethylamine (1.9 mL, 13.9 mmol). After 24 hrs, the reaction mixture was diluted with EtOAc and worked up with DI water. The organic phase was washed with brine, dried over MgSO4, and concentrated to dryness and purified by LC-MS. The resulting (Z)-tert-butyl 2-(1-(tert-butoxycarbonyl)-3-isopropyl-5-oxo-1H-pyrazol-4(5H)-ylidene)-4-chloroquinoline-1(2H)-carboxylate (0.072 g, 0.14 mmol) was stirred in ethanol and 4-aminothiophenol was added. The reaction mixture was heated at 30° C. for 4 hrs, concentrated to dryness, and carried out to the next step without further purification. The resulting (Z)-tert-butyl 4-(4-aminophenylthio)-2-(1-(tert-butoxycarbonyl)-3-isopropyl-5-oxo-1H-pyrazol-4(5H)-ylidene)quinoline-1(2H)-carboxylate was dissolved in pyridine (1-2 mL) and treated with methanesulfonyl chloride (0.035 mL, 0.44 mmol). After 1 hr, the solvent was evaporated and the solid redissolved in dichloromethane. Trifluoroacetic acid (0.9 mL) was added dropwise. The final compound was purified by LC-MS to yield Example 21. 1H NMR (400 MHz, DMSO-d6) δ ppm 0.99 (d, J=6.82 Hz, 6H) 2.58 (bs, 1H) 3.17 (s, 3H) 6.69 (s, 1H) 7.44 (d, J=8.59 Hz, 2H) 7.63 (t, J=7.58 Hz, 1H) 7.72 (d, J=8.59 Hz, 2H) 7.83-7.94 (m, 2H) 8.13 (d, J=8.34 Hz, 1H) 10.40 (s, 1H); ESI-MS: m/z calc'd for C22H22N4O3S2 454.57. found 455.2 (M+H)+.

Workup

  1. washThe organic phase was washed with brine
  2. dry with materialdried over MgSO4
  3. concentrationconcentrated to dryness
  4. custompurified by LC-MS
  5. concentrationconcentrated to dryness
  6. customcarried out to the next step without further purification
  7. dissolutionThe resulting (Z)-tert-butyl 4-(4-aminophenylthio)-2-(1-(tert-butoxycarbonyl)-3-isopropyl-5-oxo-1H-pyrazol-4(5H)-ylidene)quinoline-1(2H)-carboxylate was dissolved in pyridine (1-2 mL)
  8. waitAfter 1 hr
  9. customthe solvent was evaporated
  10. dissolutionthe solid redissolved in dichloromethane
  11. additionTrifluoroacetic acid (0.9 mL) was added dropwise
  12. customThe final compound was purified by LC-MS
  13. customto yield Example 21

Sources & evidence

ORD record
ord-a9dce5f502274216aa32cbef8a184d6c
Source dataset
uspto-grants-2009_06
Patent number
US07550598B2

Reaction notes

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