1,2-Diaminocyclohexane → HCID 131734379, compound

HRID 1507547Notes

Reaction equation

HRID 1507547 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.[CH:39]1([NH2:46])[CH2:44][CH2:43][CH2:42][CH2:41][CH:40]1[NH2:45]>C1(C)C=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]>[NH2:45][CH:40]1[CH2:41][CH2:42][CH2:43][CH2:44][CH:39]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 2

HCID 46101,2-DiaminocyclohexaneHCID 117683821HCID 117683821, compound

Product 1

HCID 131734379HCID 131734379, compound

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 312751,4-DioxaneSolvent

Procedure

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 (200 mg, 0.36 mmol, 1.00 equiv), cyclohexane-1,2-diamine (112.9 mg, 0.99 mmol, 3.00 equiv), NaOBu-t (63.4 mg, 0.66 mmol, 2.00 equiv), tris(dibenzylideneacetone)dipalladium (30.2 mg, 0.03 mmol, 0.10 equiv) and O-biphenyl(t-Bu)2P (11.8 mg, 0.04 mmol, 0.12 equiv) in toluene (12.0 mL) were dissolved in dioxane (2 mL) and heated to reflux for 18 h. The mixture was cooled to room temperature and concentrated. The crude product was purified by flash chromatography on silica gel, eluting with a mixture of 6-50% ethyl acetate in petroleum ether (15:1-2:1) to provide the title compound as a yellow solid. MS, m/z:[M+H]+ (ESI): 639.

Workup

  1. temperatureheated
  2. temperatureto reflux for 18 h
  3. concentrationconcentrated
  4. customThe crude product was purified by flash chromatography on silica gel
  5. washeluting with a mixture of 6-50% ethyl acetate in petroleum ether (15:1-2:1)

Sources & evidence

ORD record
ord-e3e937d54adf46d1b8b4cac5d52d05d3
Source dataset
uspto-grants-2015_12
Patent number
US09221809B2

Reaction notes

Loading…