Potassium Carbonate → (S)-3-(3-(azetidin-1-yl)-3-methylbut-1-ynyl)-7-(pyridin-3-yl)-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-oxazol]-2'-amine

HRID 1970385Notes

Reaction equation

HRID 1970385 reaction equation
C(=O)([O-])[O-].[K+].[K+].Br[C:8]1[CH:9]=[C:10]2[C@:21]3([CH2:25][O:24][C:23]([NH2:26])=[N:22]3)[C:20]3[C:15](=[CH:16][CH:17]=[C:18]([C:27]4[CH:28]=[N:29][CH:30]=[CH:31][CH:32]=4)[CH:19]=3)[O:14][C:11]2=[N:12][CH:13]=1.Cl.[NH:34]1[CH2:37][CH2:36][CH2:35]1.Cl[C:39]([CH3:43])([CH3:42])[C:40]#[CH:41]>[Cu]I.O.CN(C=O)C>[N:34]1([C:39]([CH3:43])([CH3:42])[C:40]#[C:41][C:8]2[CH:9]=[C:10]3[C@:21]4([CH2:25][O:24][C:23]([NH2:26])=[N:22]4)[C:20]4[C:15](=[CH:16][CH:17]=[C:18]([C:27]5[CH:28]=[N:29][CH:30]=[CH:31][CH:32]=5)[CH:19]=4)[O:14][C:11]3=[N:12][CH:13]=2)[CH2:37][CH2:36][CH2:35]1

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 706791-Butyne, 3-chloro-3-methyl-HCID 12308726Azetidine hydrochlorideHCID 67241561(5S)-3-bromo-7-(3-pyridinyl)spiro[chromeno[2,3-b]pyridine-5,4'-[1,3]oxazol]-2'-amine

Product 1

HCID 58466321(S)-3-(3-(azetidin-1-yl)-3-methylbut-1-ynyl)-7-(pyridin-3-yl)-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-oxazol]-2'-amine

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A vial charged with potassium carbonate (0.338 g, 2.444 mmol), (S)-3-bromo-7-(pyridin-3-yl)-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-oxazol]-2′-amine (0.100 g, 0.244 mmol), azetidine hydrochloride (0.209 g, 3.67 mmol), copper(i) iodide (4.65 mg, 0.024 mmol), and palladiumtetrakistriphenylphosphine (0.028 g, 0.024 mmol) was treated with 2 mL DMF and was thoroughly degassed with argon gas. 3-chloro-3-methylbut-1-yne (0.125 g, 1.222 mmol) was added, the vial was placed under argon, and was heated to 80° C. for 4 hours. The reaction mixture was poured into water and was extracted with EtOAc. The organics were washed with brine, dried over MgSO4 and concentrated. Purification of the crude residue by column chromatography gave (S)-3-(3-(azetidin-1-yl)-3-methylbut-1-ynyl)-7-(pyridin-3-yl)-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-oxazol]-2′-amine.

Workup

  1. customwas thoroughly degassed with argon gas
  2. extractionwas extracted with EtOAc
  3. washThe organics were washed with brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated
  6. customPurification of the crude residue by column chromatography

Sources & evidence

ORD record
ord-e0b0cb19b1924b718d70c951b5a216da
Source dataset
uspto-grants-2013_04
Patent number
US08426447B2

Reaction notes

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