2-Methyl-3-butyn-2-ol → 4-(2'-amino-7-bromo-8-fluoro-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-oxazole]-3-yl)-2-methylbut-3-yn-2-ol

HRID 335892Notes

Reaction equation

HRID 335892 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:16]3([CH2:20][O:19][C:18]([NH2:21])=[N:17]3)[C:15]3[C:10](=[N:11][CH:12]=[C:13](I)[CH:14]=3)[O:9][C:5]2=[CH:6][C:7]=1[F:8].[CH3:23][C:24]([OH:28])([C:26]#[CH:27])[CH3:25]>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.[Cu]I.CN(C=O)C>[NH2:21][C:18]1[O:19][CH2:20][C:16]2([C:15]3[C:10](=[N:11][CH:12]=[C:13]([C:27]#[C:26][C:24]([CH3:25])([OH:28])[CH3:23])[CH:14]=3)[O:9][C:5]3[C:4]2=[CH:3][C:2]([Br:1])=[C:7]([F:8])[CH:6]=3)[N:17]=1

Participants

6

Reactant 2

HCID 82582-Methyl-3-butyn-2-olHCID 673830077-bromo-8-fluoro-3-iodo-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-oxazol]-2'-amine

Product 1

HCID 673829024-(2'-amino-7-bromo-8-fluoro-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-oxazole]-3-yl)-2-methylbut-3-yn-2-ol

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

A vial charged with Pd(PPh3)4 (0.485 g, 0.420 mmol), copper(i) iodide (0.080 g, 0.420 mmol), 7-bromo-8-fluoro-3-iodo-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-oxazol]-2′-amine (2.000 g, 4.20 mmol), 2-methylbut-3-yn-2-ol (0.353 g, 4.20 mmol) and 9 mL DMF was degassed with argon and treated with DIPA (2.99 mL, 21.01 mmol). The resulting black mixture was allowed to stir at RT for 3 hours. The reaction mixture was then poured into water (25 mL) and extracted with EtOAc (3×30 mL). The organics were dried over MgSO4 and concentrated in vacuo. Purification of the crude residue by column chromatography [0-50% (9:1 CH2Cl2:MeOH)/CH2Cl2] provided 4-(2′-amino-7-bromo-8-fluoro-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-oxazole]-3-yl)-2-methylbut-3-yn-2-ol.

Workup

  1. customwas degassed with argon
  2. additiontreated with DIPA (2.99 mL, 21.01 mmol)
  3. additionThe reaction mixture was then poured into water (25 mL)
  4. extractionextracted with EtOAc (3×30 mL)
  5. dry with materialThe organics were dried over MgSO4
  6. concentrationconcentrated in vacuo
  7. customPurification of the crude residue by column chromatography [0-50% (9:1 CH2Cl2:MeOH)/CH2Cl2]

Sources & evidence

ORD record
ord-78e78f8612b245c0b13d3155fcc113f2
Source dataset
uspto-grants-2014_11
Patent number
US08883782B2

Reaction notes

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