Dimethylformamide → (S)-4-(2-amino-2'-((3-methyloxetan-3-yl)methoxy)-7'-(pyridin-3-yl)-5H-spiro[oxazole-4,9'-xanthene]-1'-yl)-2-methylbut-3-yn-2-ol

HRID 335868Notes

Reaction equation

HRID 335868 reaction equation
Br[C:2]1[C:15]2[C@:14]3([CH2:19][O:18][C:17]([NH2:20])=[N:16]3)[C:13]3[C:8](=[CH:9][CH:10]=[C:11]([C:21]4[CH:22]=[N:23][CH:24]=[CH:25][CH:26]=4)[CH:12]=3)[O:7][C:6]=2[CH:5]=[CH:4][C:3]=1[O:27][CH2:28][C:29]1([CH3:33])[CH2:32][O:31][CH2:30]1.[CH3:34][C:35]([OH:39])([C:37]#[CH:38])[CH3:36].CN(C=O)C.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>[NH2:20][C:17]1[O:18][CH2:19][C@@:14]2([N:16]=1)[C:15]1[C:2]([C:38]#[C:37][C:35]([CH3:36])([OH:39])[CH3:34])=[C:3]([O:27][CH2:28][C:29]3([CH3:33])[CH2:32][O:31][CH2:30]3)[CH:4]=[CH:5][C:6]=1[O:7][C:8]1[C:13]2=[CH:12][C:11]([C:21]2[CH:22]=[N:23][CH:24]=[CH:25][CH:26]=2)=[CH:10][CH:9]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 7912DiisopropylamineHCID 82582-Methyl-3-butyn-2-olHCID 67438988(S)-1'-bromo-2'-((3-methyloxetan-3-yl)methoxy)-7'-(pyridin-3-yl)-5H-spiro[oxazole-4,9'-xanthen]-2-amine

Product 1

HCID 58466143(S)-4-(2-amino-2'-((3-methyloxetan-3-yl)methoxy)-7'-(pyridin-3-yl)-5H-spiro[oxazole-4,9'-xanthene]-1'-yl)-2-methylbut-3-yn-2-ol

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
90 °C

Procedure

A resealable tube was charged with (S)-1′-bromo-2′-((3-methyloxetan-3-yl)methoxy)-7′-(pyridin-3-yl)-5H-spiro[oxazole-4,9′-xanthen]-2-amine (300 mg, 0.590 mmol), 2-methyl-3-butyn-2-ol (248 mg, 2.95 mmol), tetrakis(triphenylphosphine)palladium (68.2 mg, 0.059 mmol) and copper(i) iodide (22.48 mg, 0.118 mmol). To this were added DMF (1180 μL, 0.590 mmol) and diisopropylamine (1241 μL, 8.85 mmol). The reaction was flushed with argon, sealed and heated at 90° C. for 1.5 hours. The reaction was diluted with water (100 mL) and poured into a separatory funnel containing EtOAc (50 mL). The layers were separated and the aqueous layer was extracted with ethyl acetate (3×25 mL). The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo to provide a brown oil that was purified by silica gel chromatography (Redi-Sep pre-packed silica gel column (40 g), 0-100% CH2Cl2 to 10:1 methanol in methylenechloride with 0.1% ammonium hydroxide) to provide (S)-4-(2-amino-2′-((3-methyloxetan-3-yl)methoxy)-7′-(pyridin-3-yl)-5H-spiro[oxazole-4,9′-xanthene]-1′-yl)-2-methylbut-3-yn-2-ol as a light yellow solid. MS m/z=512.2 [M+H].

Workup

  1. customThe reaction was flushed with argon
  2. customsealed
  3. additionThe reaction was diluted with water (100 mL)
  4. additionpoured into a separatory funnel
  5. additioncontaining EtOAc (50 mL)
  6. customThe layers were separated
  7. extractionthe aqueous layer was extracted with ethyl acetate (3×25 mL)
  8. washThe combined organic layers were washed with brine
  9. dry with materialdried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customto provide a brown oil that
  13. customwas purified by silica gel chromatography (Redi-Sep pre-packed silica gel column (40 g), 0-100% CH2Cl2 to 10:1 methanol in methylenechloride with 0.1% ammonium hydroxide)

Sources & evidence

ORD record
ord-dbeea912c0bd4ce783f680357e185ad3
Source dataset
uspto-grants-2014_11
Patent number
US08883782B2

Reaction notes

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