Dimethylformamide → (S)-3-bromo-7-(3,3-dimethylbut-1-ynyl)-2',6'-dihydrospiro[chromeno[2,3-b]pyridine-5,3'-[1,4]oxazin]-5'-amine

HRID 455677Notes

Reaction equation

HRID 455677 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C@@:15]3([N:20]=[C:19]([NH2:21])[CH2:18][O:17][CH2:16]3)[C:14]3[C:9](=[CH:10][CH:11]=[C:12](I)[CH:13]=3)[O:8][C:5]2=[N:6][CH:7]=1.C(NC(C)C)(C)C.[CH3:30][C:31]([CH3:35])([CH3:34])[C:32]#[CH:33].CN(C=O)C>CC1OCCC1.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>[Br:1][C:2]1[CH:3]=[C:4]2[C@@:15]3([N:20]=[C:19]([NH2:21])[CH2:18][O:17][CH2:16]3)[C:14]3[C:9](=[CH:10][CH:11]=[C:12]([C:33]#[C:32][C:31]([CH3:35])([CH3:34])[CH3:30])[CH:13]=3)[O:8][C:5]2=[N:6][CH:7]=1

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 7912DiisopropylamineHCID 135123,3-Dimethyl-1-butyneHCID 58465904(S)-3-bromo-7-iodo-2',6'-dihydrospiro[chromeno[2,3-b]pyridine-5,3'-[1,4]oxazin]-5'-amine

Product 1

HCID 67387294(S)-3-bromo-7-(3,3-dimethylbut-1-ynyl)-2',6'-dihydrospiro[chromeno[2,3-b]pyridine-5,3'-[1,4]oxazin]-5'-amineYield 25.6%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 73012-MethyltetrahydrofuranSolvent

Conditions

Temperature
90 °C

Procedure

A vial was charged with (S)-3-bromo-7-iodo-2′,6′-dihydrospiro[chromeno[2,3-b]pyridine-5,3′-[1,4]oxazin]-5′-amine, diisopropylamine (0.785 mL, 5.51 mmol), Pd(PPh3)4 (0.127 g, 0.110 mmol), copper(I) iodide (0.021 g, 0.110 mmol), and 3,3-dimethyl-1-butyne (0.203 mL, 1.652 mmol). DMF (3 mL) were added, the vial was sealed under argon and heated to 90° C. for 60 minutes. The reaction mixture was diluted with 2-MeTHF then washed with water. The organics were dried over MgSO4 and concentrated. Purification of the crude residue by column chromatography gave (S)-3-bromo-7-(3,3-dimethylbut-1-ynyl)-2′,6′-dihydrospiro[chromeno[2,3-b]pyridine-5,3′-[1,4]oxazin]-5′-amine (0.120 g, 0.281 mmol, 25.6% yield) as a white solid.

Workup

  1. customthe vial was sealed under argon
  2. washthen washed with water
  3. dry with materialThe organics were dried over MgSO4
  4. concentrationconcentrated
  5. customPurification of the crude residue by column chromatography

Sources & evidence

ORD record
ord-e663f198b23947f1a5904990942710d6
Source dataset
uspto-grants-2013_07
Patent number
US08497264B2

Reaction notes

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