HCID 76694874, compound → HCID 68447558, compound

HRID 1867258Notes

Reaction equation

HRID 1867258 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[O:10][CH2:9][CH:8]3[C:11]([CH2:26][CH2:27][CH2:28][OH:29])([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)[C:12]([C:14](N(OC)C)=[O:15])=[N:13][N:7]3[C:6]=2[CH:30]=1.[CH3:31][Mg]Br>C1COCC1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[O:10][CH2:9][CH:8]3[C:11]([CH2:26][CH2:27][CH2:28][OH:29])([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)[C:12]([C:14](=[O:15])[CH3:31])=[N:13][N:7]3[C:6]=2[CH:30]=1

Participants

5

Reactant 3

HCID 76694874HCID 76694874, compoundHCID 178418573HCID 178418573, compoundHCID 178418689HCID 178418689, compound

Product 1

HCID 68447558HCID 68447558, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

8-Chloro-3-(3-hydroxypropyl)-N-methoxy-N-methyl-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazine-2-carboxamide (4-3; a racemic mixture, 37 mg, 86 μmol) was dissolved in anhydrous THF (1 mL) and cooled to −78° C. Methylmagnesium bromide (0.25 mL, 258 μmol) was added and the reaction stirred to 25° C. An additional portion of MeMgBr (0.16 mL, 165 mmol) was added and the reaction stirred 1 h. Upon completion the reaction was quenched by the addition of NH4CL (1 mL) and extracted with EtOAc (3×5mL). The combined organic extracts were dried (MgSO4), filtered and concentrated. Flash column chromatography (ISCO Redisep 0-100% EtOAc/hexanes gradient) provided 1-[8-chloro-3-(3-hydroxypropyl)-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazin-2-yl]ethanone (4-4; a racemic mixture) and (4-10; a racemic mixture) as a side product. 1H NMR (300 MHz, CDCl3) δ 7.56 (d, J=2.4 Hz 1H), 7.32-7.20 (m, 3H), 7.07 (m, 2H), 6.85 (dd, J=8.4, 2.4 Hz, 1H), 6.77 (d, J=8.4 Hz, 1H), 4.15 (dd, J=11.3, 3.8 Hz, 1H), 3.73 (dd, J=11.0, 3.8 Hz, 1H), 3.73 (br s, 1H), 2.93 (t, J=11.0 Hz, 1H), 2.56 (dt, J=12.2, 4.0 Hz, 1H), 2.56 (s, 3H), 2.42 (dt, J=12.9, 4.6 Hz, 1H), 1.72 (m, 1H), 1.40 (m, 3H); MS (M+H+, C21H21ClN2O3) 385.4 found 385.9 required.

Workup

  1. stirringthe reaction stirred 1 h
  2. customUpon completion the reaction was quenched by the addition of NH4CL (1 mL)
  3. extractionextracted with EtOAc (3×5mL)
  4. dry with materialThe combined organic extracts were dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-70174f39de5b4552a0d603d2352fa198
Source dataset
uspto-grants-2009_12
Patent number
US07632833B2

Reaction notes

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