1,2-Diaminocyclohexane, cis- → HCID 117677783, compound

HRID 1507548Notes

Reaction equation

HRID 1507548 reaction equation
Cl[C:2]1[C:7]2[N:8]=[C:9]([C:11]3[C:12]([NH:25][C@@H:26]4[CH2:31][CH2:30][CH2:29][N:28]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:27]4)=[N:13][C:14]([N:19]4[CH2:24][CH2:23][O:22][CH2:21][CH2:20]4)=[N:15][C:16]=3[O:17][CH3:18])[S:10][C:6]=2[CH:5]=[CH:4][CH:3]=1.[NH2:39][C@@H:40]1[CH2:45][CH2:44][CH2:43][CH2:42][C@@H:41]1[NH2:46].CC([O-])(C)C.[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].C1(C)C=CC=CC=1>[NH2:39][C@H:40]1[CH2:45][CH2:44][CH2:43][CH2:42][C@H:41]1[NH:46][C:2]1[C:7]2[N:8]=[C:9]([C:11]3[C:12]([NH:25][C@@H:26]4[CH2:31][CH2:30][CH2:29][N:28]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:27]4)=[N:13][C:14]([N:19]4[CH2:24][CH2:23][O:22][CH2:21][CH2:20]4)=[N:15][C:16]=3[O:17][CH3:18])[S:10][C:6]=2[CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 3429171,2-Diaminocyclohexane, cis-HCID 23676156Sodium t-butoxideHCID 117683821HCID 117683821, compound

Product 1

HCID 117677783HCID 117677783, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
95 °C

Procedure

Into a 50-mL round-bottom flask purged and maintained with an inert atmosphere of nitrogen was placed tert-butyl (3R)-3-[[5-(4-chloro-1,3-benzothiazol-2-yl)-6-methoxy-2-(morpholin-4-yl)pyrimidin-4-yl]amino]piperidine-1-carboxylate (180.0 mg, 0.32 mmol, 1.00 equiv), cis-1,2-diaminocyclohexane (109.9 mg, 0.96 mmol, 3.00 equiv), sodium 2-methylpropan-2-olate (61.5 mg, 0.64 mmol, 2.00 equiv) and toluene (8.0 mL). tris(dibenzylideneacetone)dipalladium (30.0 mg, 0.03 mmol, 0.10 equiv), and o-biphenyl(t-Bu)2P (19.1 mg, 0.06 mmol, 0.20 equiv) were added. And nitrogen was bubbled in for 5 min. The resulting mixture was stirred for 12 h at 95° C. in an oil bath. After cooled down, the reaction mixture was quenched by the addition of 30.0 mL of water, and extracted with ethyl acetate (3×30.0 mL). The combined organic layers were washed with brine and dried over anhydrous sodium sulfate. After filtered and concentrated under reduced pressure, the residue was purified by flash chromatography on silica gel, eluting with a mixture of 10-100% ethyl acetate in petroleum ether to give the title compounds as a white solid. MS m/z [M+H]+ (ESI): 639.

Workup

  1. customInto a 50-mL round-bottom flask purged
  2. temperaturemaintained with an inert atmosphere of nitrogen
  3. customAnd nitrogen was bubbled in for 5 min
  4. temperatureAfter cooled down
  5. customthe reaction mixture was quenched by the addition of 30.0 mL of water
  6. extractionextracted with ethyl acetate (3×30.0 mL)
  7. washThe combined organic layers were washed with brine
  8. dry with materialdried over anhydrous sodium sulfate
  9. filtrationAfter filtered
  10. concentrationconcentrated under reduced pressure
  11. customthe residue was purified by flash chromatography on silica gel
  12. washeluting with a mixture of 10-100% ethyl acetate in petroleum ether

Sources & evidence

ORD record
ord-866992dcf82d49b2a909001f7396a7dd
Source dataset
uspto-grants-2015_12
Patent number
US09221809B2

Reaction notes

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