Dimethylformamide → (S)-4-(2'-amino-7-(pyrimidin-5-yl)-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-oxazole]-3-yl)-2-methylbut-3-yn-2-ol

HRID 335765Notes

Reaction equation

HRID 335765 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[C:9](=[CH:10][CH:11]=[C:12]([C:21]4[CH:22]=[N:23][CH:24]=[N:25][CH:26]=4)[CH:13]=3)[O:8][C:5]2=[N:6][CH:7]=1.C1COCC1.CN(C=O)C.[CH3:37][C:38]([OH:42])([C:40]#[CH:41])[CH3:39]>O.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>[NH2:20][C:17]1[O:18][CH2:19][C@:15]2([C:4]3[C:5](=[N:6][CH:7]=[C:2]([C:41]#[C:40][C:38]([CH3:39])([OH:42])[CH3:37])[CH:3]=3)[O:8][C:9]3[C:14]2=[CH:13][C:12]([C:21]2[CH:22]=[N:23][CH:24]=[N:25][CH:26]=2)=[CH:11][CH:10]=3)[N:16]=1

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 8028TetrahydrofuranHCID 82582-Methyl-3-butyn-2-olHCID 67241433(S)-3-bromo-7-(pyrimidin-5-yl)-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-oxazol]-2'-amine

Product 1

HCID 67383136(S)-4-(2'-amino-7-(pyrimidin-5-yl)-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 962WaterSolvent

Conditions

Temperature
110 °C

Procedure

Combined (S)-3-bromo-7-(pyrimidin-5-yl)-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-oxazol]-2′-amine (99 mg, 0.242 mmol), tetrakis(triphenylphosphine)palladium (28.0 mg, 0.024 mmol), copper(i) iodide (4.61 mg, 0.024 mmol) and THF (969 μL, 0.242 mmol) and DMF (969 μL, 0.242 mmol). Added DIPA (679 μL, 4.85 mmol) then 2-methylbut-3-yn-2-ol (118 μL, 1.211 mmol) and flushed the reaction tube with argon. Sealed and heated at 110° C. for 2 hours. The mixture was diluted with water and extracted with EtOAc (3×). The combined organic extracts were dried over sodium sulfate, filtered, and evaporated. The residue was purified by chromatography on a 25-g SNAP column, eluting with 0-100% of a 90:10:1 mixture of DCM/MeOH/NH4OH to give (S)-4-(2′-amino-7-(pyrimidin-5-yl)-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-oxazole]-3-yl)-2-methylbut-3-yn-2-ol as a white solid after evaporation from DCM/hexane.

Workup

  1. customSealed
  2. extractionextracted with EtOAc (3×)
  3. dry with materialThe combined organic extracts were dried over sodium sulfate
  4. filtrationfiltered
  5. customevaporated
  6. customThe residue was purified by chromatography on a 25-g SNAP column
  7. washeluting with 0-100% of a 90:10:1 mixture of DCM/MeOH/NH4OH

Sources & evidence

ORD record
ord-cdd213f431204c14869100646154b81d
Source dataset
uspto-grants-2014_11
Patent number
US08883782B2

Reaction notes

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