Morpholine → HCID 16048985, compound

HRID 1364163Notes

Reaction equation

HRID 1364163 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH:17]=[C:16]3[C:10]([CH2:11][CH2:12][N:13]([CH:18]4[CH2:21][CH2:20][CH2:19]4)[CH2:14][CH2:15]3)=[N:9]2)=[CH:4][CH:3]=1.[NH:22]1[CH2:27][CH2:26][O:25][CH2:24][CH2:23]1.C(=O)([O-])[O-].[Cs+].[Cs+].CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH:18]1([N:13]2[CH2:14][CH2:15][C:16]3=[CH:17][N:8]([C:5]4[CH:6]=[CH:7][C:2]([N:22]5[CH2:27][CH2:26][O:25][CH2:24][CH2:23]5)=[CH:3][CH:4]=4)[N:9]=[C:10]3[CH2:11][CH2:12]2)[CH2:21][CH2:20][CH2:19]1

Participants

7

Reactant 4

HCID 8083Morpholine2×HCID 10796Cesium carbonate2×HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)2×HCID 16048914HCID 16048914, compound

Product 1

HCID 16048985HCID 16048985, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 2-(4-bromophenyl)-6-cyclobutyl-2,4,5,6,7,8-hexahydropyrazolo[3,4-d]azepine (may be prepared as described in Example 35) (80 mg, 0.23 mmol), morpholine (40 μl, 0.46 mmol), cesium carbonate (115 mg, 0.35 mmol), tris(dibenzylideneacetone)dipalladium(0) (10 mg, 0.01 mmol) and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphane) (20 mg, 0.035 mmol) in dioxane (2 ml) was heated in the microwave (normal absorption) at 100° C. for 2 hours. The same amounts again of morpholine, cesium carbonate, tris(dibenzylideneacetone)dipalladium(0) and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphane) were added and the mixture heated in the microwave at 150° C. for 2 hours. The reaction mixture was purified by SCX cartridge, followed by Mass Directed Autopreparation and column chromatography on silica gel, eluting with a mixture of 2M ammonia in methanol/dichloromethane (0-5%) to afford the title compound (E39). MS (ES+) m/e 353 [M+H]+.

Workup

  1. temperaturethe mixture heated in the microwave at 150° C. for 2 hours
  2. customThe reaction mixture was purified by SCX cartridge
  3. washeluting with a mixture of 2M ammonia in methanol/dichloromethane (0-5%)

Sources & evidence

ORD record
ord-4cbb086583524aab83651318eea80f79
Source dataset
uspto-grants-2011_02
Patent number
US07888347B2

Reaction notes

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