Cesium carbonate → HCID 178513661, compound

HRID 2070888Notes

Reaction equation

HRID 2070888 reaction equation
C(C1C=CC(NC2N=C3C=CC=C([NH:18][C@@H:19]4[CH2:24][CH2:23][C@H:22]([NH:25]C(=O)OC(C)(C)C)[CH2:21][CH2:20]4)N3N=2)=CC=1)#N.Br[C:35]1[N:40]2[N:41]=[C:42]([NH:44][C:45]3[CH:52]=[CH:51][C:48]([C:49]#[N:50])=[CH:47][CH:46]=3)[N:43]=[C:39]2[CH:38]=[CH:37][CH:36]=1.N[C@@H]1CC[C@H](NC(=O)[O:62]C(C)(C)C)CC1.C(=O)([O-])[O-].[Cs+].[Cs+].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1>O1CCOCC1.[Cl-].[Na+].O>[NH2:18][C@@H:19]1[CH2:24][CH2:23][C@H:22]([NH:25][C:35]2[N:40]3[N:41]=[C:42]([NH:44][C:45]4[CH:52]=[CH:51][C:48]([C:49]([NH2:50])=[O:62])=[CH:47][CH:46]=4)[N:43]=[C:39]3[CH:38]=[CH:37][CH:36]=2)[CH2:21][CH2:20]1

Participants

8

Reactant 5

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 86640816HCID 86640816, compoundHCID 178418966HCID 178418966, compoundHCID 178453995HCID 178453995, compound

Product 1

HCID 178513661HCID 178513661, compoundYield 29%

Reagents, catalysts & solvents 2

HCID 312751,4-DioxaneSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
100 °C

Procedure

tert-Butyl cis-4-(2-(4-cyanophenylamino)-[1,2,4]triazolo[1,5-a]pyridin-5-ylamino)cyclohexylcarbamate. To an orange solution of 4-(5-bromo-[1,2,4]triazolo[1,5-a]pyridin-2-ylamino)benzonitrile (0.200 g, 0.637 mmol) in dioxane (10 mL) was added tert-butyl cis-4-aminocyclohexylcarbamate (0.273 g, 1.273 mmol), cesium carbonate (0.415 g, 1.273 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (0.074 g, 0.127 mmol) and tris(dibezylideneacetone)palladium (0.061 g, 0.0669 mmol) at room temperature under nitrogen. The reaction mixture was heated at 100° C. for 1 h under nitrogen. Upon completion of the reaction, as indicated by LCMS, the reaction mixture was poured into brine, and extracted with ethyl acetate several times. The combined organic layers were dried over anhydrous magnesium sulfate and concentrated. The crude mixture was purified by column chromatography (eluting with 0-80% ethyl acetate in hexanes) to give the title compound as a tan solid (0.082 g, 29% yield). 1H NMR (400 MHz, DMSO-d6) δ (ppm) 10.22 (s, 1H), 7.89 (d, 2H, J=8 Hz), 7.73 (d, 2H, J=8 Hz), 7.46 (t, 1H, J=8 Hz), 6.81 (d, 1H, J=8 Hz), 6.25 (d, 1H, J=8 Hz), 6.02 (d, 1H, J=8 Hz), 3.71-3.64 (m, 1H), 3.56-3.34 (m, 1H), 1.90-1.73 (m, 4H), 1.66-1.61 (m, 4H), 1.40 (s, 9H); MS (ESI) m/z 448.53 [M+1]+.

Workup

  1. customUpon completion of the reaction
  2. extractionextracted with ethyl acetate several times
  3. dry with materialThe combined organic layers were dried over anhydrous magnesium sulfate
  4. concentrationconcentrated
  5. customThe crude mixture was purified by column chromatography (eluting with 0-80% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-9cbb253ba0264e9dba577c12f7ba1957
Source dataset
uspto-grants-2012_10
Patent number
US08299056B2

Reaction notes

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