Potassium Carbonate → HCID 86658462, compound

HRID 335857Notes

Reaction equation

HRID 335857 reaction equation
C([O-])(=O)C.[K+].FC(F)(F)S(O[C:12]1[CH:13]=[C:14]2[C@@:25]3([CH2:29][O:28][C:27]([NH2:30])=[N:26]3)[C:24]3[C:19](=[N:20][CH:21]=[C:22](C#CC4(C)COC4)[CH:23]=3)[O:18][C:15]2=[CH:16][CH:17]=1)(=O)=O.B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.BrC1C=NC=CC=1F.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.CCOC(C)=O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl.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.O>[O:28]1[CH2:29][C:25]2([C:24]3[C:19](=[N:20][CH:21]=[CH:22][CH:23]=3)[O:18][C:15]3[C:14]2=[CH:13][CH:12]=[CH:17][CH:16]=3)[N:26]=[C:27]1[NH2:30]

Participants

11

Reactant 5

HCID 11430Potassium CarbonateHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 27627793-bromo-4-fluoropyridineHCID 86640736HCID 86640736, compound

Product 1

HCID 86658462HCID 86658462, compound

Reagents, catalysts & solvents 5

HCID 178418397HCID 178418397, compoundCatalystHCID 178418807HCID 178418807, compoundCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

A solution of potassium acetate (0.210 g, 2.140 mmol), PdCl2(dppf)-CH2Cl2 adduct (0.022 g, 0.027 mmol), (S)-2′-amino-3-((3-methyloxetan-3-yl)ethynyl)-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-oxazole]-7-yl trifluoromethanesulfonate (0.265 g, 0.535 mmol), and bis(pinacolato)diboron (0.143 g, 0.562 mmol) in 5 mL DMF was heated to 100° C. for 3 hours. Pd(PPh3)4 (0.031 g, 0.027 mmol) was added, followed by 3-bromo-4-fluoropyridine (0.141 g, 0.802 mmol), potassium carbonate (0.296 g, 2.140 mmol), and 2 mL water. The reaction mixture was capped with argon and was heated to 100° C. for 2 hours. After cooling to RT, the reaction mixture was diluted with EtOAc and was washed sequentially with water and brine. The organics were dried over MgSO4 and concentrated. Purification of the crude residue by column chromatography [0-100% (9:1 CH2Cl2:MeOH)/CH2Cl2] then HPLC (10-90% MeCN/H2O) provided (S)-7-(4-fluoropyridin-3-yl)-3-(3-methyloxetan-3-yl)ethynyl)-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-oxazol]-2′-amine. MS m/z=443.0 [M+H].

Workup

  1. customThe reaction mixture was capped with argon
  2. temperatureAfter cooling to RT
  3. washwas washed sequentially with water and brine
  4. dry with materialThe organics were dried over MgSO4
  5. concentrationconcentrated
  6. customPurification of the crude residue by column chromatography [0-100% (9:1 CH2Cl2:MeOH)/CH2Cl2]

Sources & evidence

ORD record
ord-2d7ceb8ab0ef4e0ca032bd1c40acdecd
Source dataset
uspto-grants-2014_11
Patent number
US08883782B2

Reaction notes

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