Water → HCID 67383293, compound

HRID 335839Notes

Reaction equation

HRID 335839 reaction equation
FC(F)(F)S(O[C:7]1[CH:20]=[C:19]2[C:10]([O:11][C:12]3[CH:13]=[CH:14][C:15]([C:26]#[C:27][C:28]([OH:31])([CH3:30])[CH3:29])=[CH:16][C:17]=3[C@@:18]32[CH2:24][O:23][C:22]([NH2:25])=[N:21]3)=[CH:9][C:8]=1[F:32])(=O)=O.[N:35]1[CH:40]=[C:39](B(O)O)[CH:38]=[N:37][CH:36]=1.C(=O)([O-])[O-].[K+].[K+].O>O1CCOCC1.CCOC(C)=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>[NH2:25][C:22]1[O:23][CH2:24][C@:18]2([N:21]=1)[C:19]1[CH:20]=[C:7]([C:39]3[CH:40]=[N:35][CH:36]=[N:37][CH:38]=3)[C:8]([F:32])=[CH:9][C:10]=1[O:11][C:12]1[C:17]2=[CH:16][C:15]([C:26]#[C:27][C:28]([CH3:29])([OH:31])[CH3:30])=[CH:14][CH:13]=1

Participants

8

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 2795193(Pyrimidin-5-yl)boronic acidHCID 86658468HCID 86658468, compound

Product 1

HCID 67383293HCID 67383293, compound

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A solution of (R)-2-amino-6′-fluoro-2′-(3-hydroxy-3-methylbut-1-ynyl)-5H-spiro[oxazole-4,9′-xanthene]-7′-yl trifluoromethanesulfonate (0.317 g, 0.633 mmol), pyrimidin-5-ylboronic acid (0.157 g, 1.267 mmol), Pd(PPh3)4 (0.037 g, 0.032 mmol), and potassium carbonate (0.438 g, 3.17 mmol) in 1.5 mL dioxane was treated with 0.5 mL water and was heated to 100° C. overnight. The reaction mixture was cooled to rt and diluted with EtOAc. The layers were separated and the organic layer was dried over MgSO4 filtered and concentrated. Purification of the crude residue by column chromatography [0-80% (9:1:0.1—CH2Cl2:MeOH:NH4OH)/CH2Cl2] gave (R)-4-(2-amino-3′-fluoro-2′-(pyrimidin-5-yl)-5H-spiro[oxazole-4,9′-xanthene]-7′-yl)-2-methylbut-3-yn-2-ol. MS m/z=431.0 [M+H].

Workup

  1. temperatureThe reaction mixture was cooled to rt
  2. customThe layers were separated
  3. dry with materialthe organic layer was dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification of the crude residue by column chromatography [0-80% (9:1:0.1—CH2Cl2:MeOH:NH4OH)/CH2Cl2]

Sources & evidence

ORD record
ord-6d4322c3f8e74035880927ba7b6765b0
Source dataset
uspto-grants-2014_11
Patent number
US08883782B2

Reaction notes

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