Potassium Carbonate → (7-Chlorospiro[benzo[b]pyrrolo[1,2-d][1,4]oxazine-4,4'-piperidine]-1'-yl)(4-cyclopropyl-3-methoxyphenyl)methanone

HRID 1908156Notes

Reaction equation

HRID 1908156 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]([N:10]2[CH2:15][CH2:14][C:13]3([O:20][C:19]4[CH:21]=[C:22]([Cl:25])[CH:23]=[CH:24][C:18]=4[N:17]4[CH:26]=[CH:27][CH:28]=[C:16]34)[CH2:12][CH2:11]2)=[O:9])=[CH:4][C:3]=1[O:29][CH3:30].[CH:31]1(B(O)O)[CH2:33][CH2:32]1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[Cl:25][C:22]1[CH:23]=[CH:24][C:18]2[N:17]3[CH:26]=[CH:27][CH:28]=[C:16]3[C:13]3([CH2:14][CH2:15][N:10]([C:8]([C:5]4[CH:6]=[CH:7][C:2]([CH:31]5[CH2:33][CH2:32]5)=[C:3]([O:29][CH3:30])[CH:4]=4)=[O:9])[CH2:11][CH2:12]3)[O:20][C:19]=2[CH:21]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 2760897Cyclopropylboronic acidHCID 58551353(4-Bromo-3-methoxy-phenyl)-(7'-chlorospiro[piperidine-4,4'-pyrrolo[2,1-c][1,4]benzoxazine]-1-yl)methanone

Product 1

HCID 58551518(7-Chlorospiro[benzo[b]pyrrolo[1,2-d][1,4]oxazine-4,4'-piperidine]-1'-yl)(4-cyclopropyl-3-methoxyphenyl)methanone

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

To a microwave vial was added Pd-FibreCat (42 mg, 0.0065 mmol), (4-bromo-3-methoxyphenyl)(7-chlorospiro[benzo[b]pyrrolo[1,2-d][1,4]oxazine-4,4′-piperidine]-1′-yl)methanone (63 mg, 0.13 mmol), cyclopropylboronic acid (17 mg, 0.19 mmol), DMF (0.7 mL), and K2CO3 (190 μL of 2.0 M, 0.39 mmol). The reaction vessel was purged with nitrogen and the mixture was heated at 120° C. overnight. The mixture was filtered and was purified by prep-HPLC (20-99% MeOH:H2O with HCl modifier) to give (7-chlorospiro[benzo[b]pyrrolo[1,2-d][1,4]oxazine-4,4′-piperidine]-1′-yl)(4-cyclopropyl-3-methoxyphenyl)methanone. ESI-MS m/z calc. 448.2. found 449.4 (M+1)+; Retention time: 3.32 minutes (4 min run).

Workup

  1. customThe reaction vessel was purged with nitrogen
  2. filtrationThe mixture was filtered
  3. customwas purified by prep-HPLC (20-99% MeOH:H2O with HCl modifier)

Sources & evidence

ORD record
ord-d5299d8dce294c22a43abd5c2db43717
Source dataset
uspto-grants-2013_12
Patent number
US08598164B2

Reaction notes

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