Diisopropylamine → (S)-4-(2-amino-5'-fluoro-2'-(2-fluoropyridin-3-yl)-5H-spiro[oxazole-4,9'-xanthene]-7'-yl)-2-methylbut-3-yn-2-ol

HRID 335831Notes

Reaction equation

HRID 335831 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]4[C:27]([F:32])=[N:28][CH:29]=[CH:30][CH:31]=4)=[CH:16][C:17]=3[C@:18]32[CH2:24][O:23][C:22]([NH2:25])=[N:21]3)=[C:9]([F:33])[CH:8]=1)(=O)=O.[CH3:36][C:37]([OH:41])([C:39]#[CH:40])[CH3:38].C(NC(C)C)(C)C>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>[NH2:25][C:22]1[O:23][CH2:24][C@:18]2([N:21]=1)[C:17]1[CH:16]=[C:15]([C:26]3[C:27]([F:32])=[N:28][CH:29]=[CH:30][CH:31]=3)[CH:14]=[CH:13][C:12]=1[O:11][C:10]1[C:19]2=[CH:20][C:7]([C:40]#[C:39][C:37]([CH3:38])([OH:41])[CH3:36])=[CH:8][C:9]=1[F:33]

Participants

7

Reactant 3

HCID 7912DiisopropylamineHCID 82582-Methyl-3-butyn-2-olHCID 86640722(S)-2-amino-5'-fluoro-2'-(2-fluoropyridin-3-yl)-5H-spiro[oxazole-4,9'-xanthene]-7'-yl trifluoromethanesulfonate

Product 1

HCID 67383734(S)-4-(2-amino-5'-fluoro-2'-(2-fluoropyridin-3-yl)-5H-spiro[oxazole-4,9'-xanthene]-7'-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

Conditions

Temperature
85 °C

Procedure

A 15 ml resealable tube was charged with (S)-2-amino-5′-fluoro-2′-(2-fluoropyridin-3-yl)-5H-spiro[oxazole-4,9′-xanthene]-7′-yl trifluoromethanesulfonate (300 mg, 0.584 mmol), tetrakis(triphenylphosphine)palladium(0) (67.5 mg, 0.058 mmol), copper(i) iodide (11.13 mg, 0.058 mmol), DMF (2922 μL), 2-methylbut-3-yn-2-ol (114 μL, 1.169 mmol) and diisopropylamine (416 μL, 2.92 mmol). The mixture was capped with argon, sealed and heated at 85° C. for 1 hr. Concentration and purification of the crude residue by silica gel chromatography (10-60% CH2Cl2/MeOH/NH4OH 90:10:1 in CH2Cl2) afforded (S)-4-(2-amino-5′-fluoro-2′-(2-fluoropyridin-3-yl)-5H-spiro[oxazole-4,9′-xanthene]-7′-yl)-2-methylbut-3-yn-2-ol. MS m/z=448.0 [M+H].

Workup

  1. customThe mixture was capped with argon
  2. customsealed
  3. concentrationConcentration and purification of the crude residue by silica gel chromatography (10-60% CH2Cl2/MeOH/NH4OH 90:10:1 in CH2Cl2)

Sources & evidence

ORD record
ord-aaa3eda660c6484996800a2459d40c52
Source dataset
uspto-grants-2014_11
Patent number
US08883782B2

Reaction notes

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