Triacetoxyperiodinane → Methyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-bromo-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-oxoacetate

HRID 1400770Notes

Reaction equation

HRID 1400770 reaction equation
[CH2:1]([O:4][C:5]1([CH3:27])[CH2:10][CH2:9][N:8]([C:11]2[N:16]3[N:17]=[C:18]([Br:20])[CH:19]=[C:15]3[N:14]=[C:13]([CH3:21])[C:12]=2[CH2:22][C:23]([O:25][CH3:26])=[O:24])[CH2:7][CH2:6]1)[CH:2]=[CH2:3].CC([OH:31])C.C(=O)=O.C[Si]([N-][Si](C)(C)C)(C)C.[K+].C1(C2ON2S(C2C=CC=CC=2)(=O)=O)C=CC=CC=1.C(=O)(O)[O-].[Na+].CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O>C1COCC1.C(Cl)Cl>[CH2:1]([O:4][C:5]1([CH3:27])[CH2:10][CH2:9][N:8]([C:11]2[N:16]3[N:17]=[C:18]([Br:20])[CH:19]=[C:15]3[N:14]=[C:13]([CH3:21])[C:12]=2[C:22](=[O:31])[C:23]([O:25][CH3:26])=[O:24])[CH2:7][CH2:6]1)[CH:2]=[CH2:3]

Participants

9

Reactant 6

HCID 159087TriacetoxyperiodinaneHCID 3204052-(Benzenesulfonyl)-3-phenyloxaziridineHCID 516892Sodium Bicarbonate2×HCID 3251421Potassium bis(trimethylsilyl)amideHCID 86586944Isopropanol carbon dioxideHCID 86710822Methyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-bromo-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)acetate

Product 1

HCID 86710823Methyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-bromo-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-oxoacetateYield 50%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of methyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-bromo-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)acetate (17.7 g, 40.5 mmol, 1 equiv) in THF (200 mL) was cooled to −78° C. (IPA/CO2). KHMDS (72 mL of a 0.91 M solution in THF, 64.9 mmol, 1.6 equiv) was added dropwise over ˜2 min. Reaction turned a deep orange color. After 30 min, 3-phenyl-2-(phenylsulfonyl)-1,2-oxaziridine (15.9 g, 60.8 mmol, 1.2 equiv) was added in a single portion. The reaction significantly darkened. After 30 min, the reaction was added to saturated aqueous sodium bicarbonate and extracted with ether (×2). The combined ether extracts were dried (MgSO4) and concentrated in vacuo to provide the crude product as a brown oil. This was taken up in DCM (200 mL) and Dess-Martin periodinane (20.6 g, 48.6 mmol, 1.2 equiv). After 30 min, the reaction was added to saturated aqueous sodium bicarbonate and extracted with DCM (×3). Combined DCM extracts were dried (Na2SO4) and concentrated in vacuo to provide the crude product. The crude product was purified via silica gel flash chromatography (0-50% EtOAc/hex) to provide methyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-bromo-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-oxoacetate (9.2 g, 50%). 1H NMR (500 MHz, CDCl3) δ 6.55 (s, 1H), 6.07-5.87 (m, 1H), 5.38 (dq, J=17.2, 1.7 Hz, 1H), 5.20 (dq, J=10.4, 1.6 Hz, 1H), 3.95-3.92 (m, 5H), 3.69 (d, J=12.6 Hz, 2H), 3.59-3.50 (m, 2H), 2.56 (s, 3H), 1.96-1.82 (m, 4H), 1.28 (s, 3H). LCMS (M+1)=450.95.

Workup

  1. customReaction
  2. customThe reaction
  3. waitAfter 30 min
  4. extractionextracted with ether (×2)
  5. dry with materialThe combined ether extracts were dried (MgSO4)
  6. concentrationconcentrated in vacuo
  7. customto provide the crude product as a brown oil
  8. waitAfter 30 min
  9. extractionextracted with DCM (×3)
  10. dry with materialCombined DCM extracts were dried (Na2SO4)
  11. concentrationconcentrated in vacuo
  12. customto provide the crude product
  13. customThe crude product was purified via silica gel flash chromatography (0-50% EtOAc/hex)

Sources & evidence

ORD record
ord-b23f852c9b744e9b9a93e4642538f3db
Source dataset
uspto-grants-2014_12
Patent number
US08906929B2

Reaction notes

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