Dichloromethane → HCID 67241930, compound

HRID 335797Notes

Reaction equation

HRID 335797 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:15]3([CH2:19][O:18][C:17]([NH2:20])=[N:16]3)[C:14]3[CH:13]=[C:12](Cl)[N:11]=[C:10]([F:22])[C:9]=3[O:8][C:5]2=[CH:6][CH:7]=1.[N:23]1[CH:28]=[CH:27][CH:26]=[C:25](B(O)O)[CH:24]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C(Cl)Cl>O1CCOCC1.O.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.Cl[Pd]Cl.C(Cl)Cl.CO>[F:22][C:10]1[C:9]2[O:8][C:5]3[C:4]([C:15]4([CH2:19][O:18][C:17]([NH2:20])=[N:16]4)[C:14]=2[CH:13]=[C:12]([C:9]2[CH:10]=[N:11][CH:12]=[CH:13][CH:14]=2)[N:11]=1)=[CH:3][C:2]([C:25]1[CH:24]=[N:23][CH:28]=[CH:27][CH:26]=1)=[CH:7][CH:6]=3

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 62657Potassium Phosphate, TribasicHCID 27343783-Pyridinylboronic acid2×HCID 58466112HCID 58466112, compound

Product 1

HCID 67241930HCID 67241930, compound

Reagents, catalysts & solvents 3

HCID 11714597Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)CatalystHCID 21226129Dichloromethane methanolSolventHCID 218864351,4-Dioxane--water (1/1)Solvent

Procedure

A mixture of 7-bromo-3-chloro-1-fluoro-5′H-spiro[chromeno[2,3-c]pyridine-5,4′-oxazol]-2′-amine (40.0 mg, 0.104 mmol), pyridin-3-ylboronic acid (21.73 mg, 0.177 mmol), bis-(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(ii) (2.95 mg, 4.16 μmol) and potassium phosphate (66.2 mg, 0.312 mmol) in 1.5 ml of dioxane/water=2:1 was heated at 120 C microwave for 20 min. LCMS showed mostly conversion to the mono coupling product. 10 mg of pyridin-3-ylboronic acid (21.73 mg, 0.177 mmol) was added and the reaction was heated at 140 C under microwave for 20 min. The reaction mixture was directly loaded to CC (SiO2, DCM to DCM/MeOH=100:1 to 100:6) to give crude final product which was further purified by prep TLC (DCM/MeOH) to give 1-fluoro-3,7-di(pyridin-3-yl)-5′H-spiro[chromeno[2,3-c]pyridine-5,4′-oxazol]-2′-amine as a white solid. MS (M+1): 426.

Workup

  1. temperaturewas heated at 120 C microwave for 20 min
  2. temperaturethe reaction was heated at 140 C under microwave for 20 min
  3. customto give crude final product which
  4. customwas further purified by prep TLC (DCM/MeOH)

Sources & evidence

ORD record
ord-c7e4cb32ecfe46b58a5108ef1e4c190c
Source dataset
uspto-grants-2014_11
Patent number
US08883782B2

Reaction notes

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