Morpholine → HCID 59380365, compound

HRID 2353842Notes

Reaction equation

HRID 2353842 reaction equation
Br[C:2]1[CH:31]=[CH:30][C:5]2[C:6]3[C:11]([NH:12][C:13]4[CH:18]=[CH:17][C:16]([O:19][CH2:20][C:21]5[CH:26]=[CH:25][CH:24]=[C:23]([F:27])[CH:22]=5)=[C:15]([Cl:28])[CH:14]=4)=[N:10][CH:9]=[N:8][C:7]=3[S:29][C:4]=2[CH:3]=1.[NH:32]1[CH2:37][CH2:36][O:35][CH2:34][CH2:33]1.[H-].[Na+]>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]>[Cl:28][C:15]1[CH:14]=[C:13]([NH:12][C:11]2[C:6]3[C:5]4[CH:30]=[CH:31][C:2]([N:32]5[CH2:37][CH2:36][O:35][CH2:34][CH2:33]5)=[CH:3][C:4]=4[S:29][C:7]=3[N:8]=[CH:9][N:10]=2)[CH:18]=[CH:17][C:16]=1[O:19][CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([F:27])[CH:22]=1

Participants

5

Reactant 3

HCID 8083MorpholineHCID 24758Sodium hydrideHCID 59380385HCID 59380385, compound

Product 1

HCID 59380365HCID 59380365, compoundYield 57.4%

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
137.5 °C

Procedure

To a stirring suspension of (7-bromo-benzo[4,5]thieno[2,3-d]pyrimidin-4-yl)-[3-chloro-4-(3-fluoro-benzyloxy)-phenyl]-amine (50 mg, 0.097 mmol) in morpholine (500 mg, 5.74 mmol) was added sodium hydride (60%, 15.5 mg, 0.388 mmol). The resulting mixture was bubbled with N2 for 2 min, followed by addition of 2-dicyclohexyphino-2′-(N,N-dimethylamino)biphenyl (1.91 mg, 4.86 μmol), and tris(dibenzylideneacetone)dipalladium (4.45 mg, 4.86 μmol). The mixture was further bubbled with N2 for 2 min, and stirred at 135-140° C. for 20 min. It was cooled to rt, and concentrated in vacuo. The residue was purified by preparative TLC (CH2Cl2/CH3OH=8/1) to give the target product (29.0 mg, 57%). 1H-NMR (DMSO-d6) δ 8.83 (s, 1H), 8.43 (s, 1H), 8.37 (d, 1H), 7.73 (d, 1H), 7.61 (d, 1H), 7.51 (q, 1H), 7.43-7.48 (m, 1H), 7.28-7.32 (m, 2H), 7.21-7.25 (m, 2H), 7.16 (m, 1H), 5.25 (s, 1H), 3.78 (t, 4H), 3.26 (t, 4H). LCMS RT=3.90 min; [M+H]+=521.1.

Workup

  1. customThe resulting mixture was bubbled with N2 for 2 min
  2. customThe mixture was further bubbled with N2 for 2 min
  3. temperatureIt was cooled to rt
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by preparative TLC (CH2Cl2/CH3OH=8/1)

Sources & evidence

ORD record
ord-b52d785f3fa64d2e966545aa5eb11ba6
Source dataset
uspto-grants-2010_07
Patent number
US07750017B2

Reaction notes

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