Sodium Carbonate → HCID 86706572, compound

HRID 2174564Notes

Reaction equation

HRID 2174564 reaction equation
[Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([OH:18])=[C:7]([N:13]3[CH:17]=[CH:16][CH:15]=[N:14]3)[C:8](=[O:12])[NH:9]2)=[CH:4][C:3]=1I.CC1(C)C(C)(C)OB([C:28]2[CH:33]=[CH:32][C:31]([C:34]3[N:35]=[C:36]([NH:39]C(=O)C)[S:37][CH:38]=3)=[CH:30][CH:29]=2)O1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[ClH:1].[NH2:39][C:36]1[S:37][CH:38]=[C:34]([C:31]2[CH:32]=[CH:33][C:28]([C:3]3[CH:4]=[C:5]4[C:10](=[CH:11][C:2]=3[Cl:1])[NH:9][C:8](=[O:12])[C:7]([N:13]3[CH:17]=[CH:16][CH:15]=[N:14]3)=[C:6]4[OH:18])=[CH:29][CH:30]=2)[N:35]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 68352388HCID 68352388, compound2×HCID 86706567HCID 86706567, compound2×

Product 1

HCID 86706572HCID 86706572, compoundYield 38.3%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

7-Chloro-4-hydroxy-6-iodo-3-(1H-pyrazol-1-yl)quinolin-2(1H)-one (Intermediate 112) (300 mg, 0.774 mmol), N-(4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)thiazol-2-yl) acetamide (Intermediate 31) (264 mg, 1.0 mmol), Pd(Ph3P)4 (8.94 mg, 7.74 μmol), 1M Na2CO3 (2.32 mL, 2.32 mmol) were mixed in 1,4-dioxane (3 mL). The reaction mixture was stirred at 120° C. for 1 h under microwave irradiation then cooled to room temperature and filtered through celite. The filtrate was diluted with water and extracted twice with DCM. The organic layers were combined, dried over Na2SO4 and concentrated under reduced pressure. The crude product was then diluted with EtOH and concentrated hydrochloric acid and the resulting mixture was heated at 90° C. overnight. The reaction mixture was cooled to room temperature then filtered. The powder was washed successively with water, EtOH and Et2O to afford the title compound 6-[4-(2-amino-1,3-thiazol-4-yl)phenyl]-7-chloro-4-hydroxy-3-(1H-pyrazol-1-yl)-2(1H)-quinolinone hydrochloride (70 mg, 19.1% yield) as a grey powder. LCMS: (M+H)+=436; Rt=2.14 min. HRMS: calculated for C21H13ClN5O2S (M−H)+: 434.0479. found: 434.0435.

Workup

  1. temperaturethen cooled to room temperature
  2. filtrationfiltered through celite
  3. additionThe filtrate was diluted with water
  4. extractionextracted twice with DCM
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated under reduced pressure
  7. additionThe crude product was then diluted with EtOH and concentrated hydrochloric acid
  8. temperaturethe resulting mixture was heated at 90° C. overnight
  9. temperatureThe reaction mixture was cooled to room temperature
  10. filtrationthen filtered
  11. washThe powder was washed successively with water, EtOH and Et2O

Sources & evidence

ORD record
ord-85ac4b2412134a9e9d77379bebfb96d7
Source dataset
uspto-grants-2015_06
Patent number
US09061998B2

Reaction notes

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