2-(Benzenesulfonyl)-3-phenyloxaziridine → Ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(3-bromophenyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-hydroxyacetate

HRID 1400753Notes

Reaction equation

HRID 1400753 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[K+].C1C[O:14]CC1.[CH2:16]([O:19][C:20]1([CH3:49])[CH2:25][CH2:24][N:23]([C:26]2[N:31]3[N:32]=[C:33]([C:35]4[CH:40]=[CH:39][CH:38]=[C:37]([Br:41])[CH:36]=4)[CH:34]=[C:30]3[N:29]=[C:28]([CH3:42])[C:27]=2[CH2:43][C:44]([O:46][CH2:47][CH3:48])=[O:45])[CH2:22][CH2:21]1)[CH:17]=[CH2:18].C1(C2ON2S(C2C=CC=CC=2)(=O)=O)C=CC=CC=1>C1COCC1>[CH2:16]([O:19][C:20]1([CH3:49])[CH2:25][CH2:24][N:23]([C:26]2[N:31]3[N:32]=[C:33]([C:35]4[CH:40]=[CH:39][CH:38]=[C:37]([Br:41])[CH:36]=4)[CH:34]=[C:30]3[N:29]=[C:28]([CH3:42])[C:27]=2[CH:43]([OH:14])[C:44]([O:46][CH2:47][CH3:48])=[O:45])[CH2:22][CH2:21]1)[CH:17]=[CH2:18]

Participants

5

Reactant 3

HCID 3204052-(Benzenesulfonyl)-3-phenyloxaziridineHCID 86624818Khmds thfHCID 86710809Ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(3-bromophenyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)acetate

Product 1

HCID 86710811Ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(3-bromophenyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-hydroxyacetateYield 82.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-78 °C

Procedure

To a stirred solution of 1M KHMDS/THF (49.3 mL, 49.3 mmol) in THF (150 mL) at −78° C. was added dropwise a THF (100 mL) solution of ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(3-bromophenyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)acetate (20 g, 37.9 mmol) over 5 min. After 30 min, a THF (100 mL) solution of 3-phenyl-2-(phenylsulfonyl)-1,2-oxaziridine (12.88 g, 49.3 mmol) was added and stirred for additional 30 min at −78° C. Then, the resulting dark reaction mixture was quenched with sat. NH4Cl (50 mL), diluted with EtOAc (200 mL), washed with water (100 mL), brine (100 mL), dried (Na2SO4), filtered and concentrated. The residue was then purified by Biotage(5-50% EtOAc/hexane) to afford ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(3-bromophenyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-hydroxyacetate (17 g, 31.3 mmol, 82% yield) as white foam. Impurities were present by NMR. Used as is in the next step without further purification. 1H NMR (500 MHz, CDCl3) δ 8.16 (t, J=1.7 Hz, 1H), 7.99-7.92 (m, 1H), 7.58-7.50 (m, 2H), 7.34 (t, J=7.9 Hz, 1H), 6.83 (s, 1H), 6.18-6.06 (m, 1H), 5.57 (d, J=5.4 Hz, 1H), 5.48 (d, J=17.0 Hz, 1H), 5.27 (d, J=10.2 Hz, 1H), 4.83 (br. s., 2H), 4.35 (dq, J=10.8, 7.1 Hz, 1H), 4.23 (dq, J=10.9, 7.1 Hz, 1H), 4.06-3.99 (m, 2H), 2.65 (s, 3H), 2.00 (d, J=14.2 Hz, 2H), 1.84 (d, J=13.4 Hz, 2H), 1.36 (s, 3H), 1.29-1.26 (m, 3H). LCMS (M+H)=545.3.

Workup

  1. customThen, the resulting dark reaction mixture
  2. customwas quenched with sat. NH4Cl (50 mL)
  3. additiondiluted with EtOAc (200 mL)
  4. washwashed with water (100 mL), brine (100 mL)
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was then purified by Biotage(5-50% EtOAc/hexane)

Sources & evidence

ORD record
ord-cd18bbd441dd4deca5e9b9211ea0eae4
Source dataset
uspto-grants-2014_12
Patent number
US08906929B2

Reaction notes

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