Methanol → (4-Methoxy-3-(methylsulfonyl)phenyl)(spiro[benzo[b]pyrrolo[1,2-d][1,4]oxazine-4,4'-piperidine]-1'-yl)methanone

HRID 1908154Notes

Reaction equation

HRID 1908154 reaction equation
F[C:2]1[CH:7]=[CH:6][C:5]([C:8]([N:10]2[CH2:27][CH2:26][C:13]3([C:18]4=[CH:19][CH:20]=[CH:21][N:17]4[C:16]4[CH:22]=[CH:23][CH:24]=[CH:25][C:15]=4[O:14]3)[CH2:12][CH2:11]2)=[O:9])=[CH:4][C:3]=1[S:28]([CH3:31])(=[O:30])=[O:29].[CH3:32][OH:33].[H-].[Na+]>CN(C=O)C>[CH3:32][O:33][C:2]1[CH:7]=[CH:6][C:5]([C:8]([N:10]2[CH2:27][CH2:26][C:13]3([O:14][C:15]4[CH:25]=[CH:24][CH:23]=[CH:22][C:16]=4[N:17]4[CH:21]=[CH:20][CH:19]=[C:18]34)[CH2:12][CH2:11]2)=[O:9])=[CH:4][C:3]=1[S:28]([CH3:31])(=[O:30])=[O:29]

Participants

5

Reactant 3

HCID 887MethanolHCID 24758Sodium hydrideHCID 58551140(4-Fluoro-3-methylsulfonyl-phenyl)-spiro[piperidine-4,4'-pyrrolo[2,1-c][1,4]benzoxazine]-1-yl-methanone

Product 1

HCID 58551251(4-Methoxy-3-(methylsulfonyl)phenyl)(spiro[benzo[b]pyrrolo[1,2-d][1,4]oxazine-4,4'-piperidine]-1'-yl)methanone

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(4-Fluoro-3-methylsulfonyl-phenyl)-spiro[piperidine-4,4′-pyrrolo[2,1-c][1,4]benzoxazine]-1-yl-methanone (44 mg, 0.10 mmol) and MeOH (12 μL, 0.30 mmol) were combined in DMF (1 mL). NaH (60%, 12 mg, 0.30 mmol) was added and the reaction mixture was stirred for 10 minutes. The mixture was filtered and was purified by reverse phase preparative liquid chromatography utilizing a gradient of 10-99% acetonitrile in water containing 5 mM hydrochloric acid to give (4-methoxy-3-(methylsulfonyl)phenyl)(spiro[benzo[b]pyrrolo[1,2-d][1,4]oxazine-4,4′-piperidine]-1′-yl)methanone. ESI-MS m/z calc. 452.1. found 453.5 (M+1)+; Retention time: 1.78 minutes (3 min run). 1H NMR (400 MHz, DMSO) δ 7.87 (d, J=2.0 Hz, 1H), 7.86-7.81 (m, 1H), 7.67 (d, J=7.6 Hz, 1H), 7.50 (s, 1H), 7.36 (d, J=8.6 Hz, 1H), 7.22-7.02 (m, 3H), 6.28 (t, J=3.1 Hz, 1H), 6.16 (d, J=2.3 Hz, 1H), 4.52-4.18 (m, 1H), 4.00 (s, 3H), 3.58 (s, 3H), 3.28 (s, 3H), 1.98 (s, 4H).

Workup

  1. filtrationThe mixture was filtered
  2. customwas purified by reverse phase preparative liquid chromatography

Sources & evidence

ORD record
ord-1d3b5c0d71ec4f289e99223ae20abf8c
Source dataset
uspto-grants-2013_12
Patent number
US08598164B2

Reaction notes

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