7-Methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene → HCID 66859615, compound

HRID 1803275Notes

Reaction equation

HRID 1803275 reaction equation
FC(F)(S(O[C:17]1[CH:31]=[C:20]2[CH2:21][CH2:22][CH:23]=[C:24]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[N:19]2[N:18]=1)(=O)=O)C(F)(F)C(F)(F)C(F)(F)F.[Cl:33][C:34]1[N:35]=[CH:36][N:37]([C:39]2[CH:45]=[CH:44][C:42]([NH2:43])=[CH:41][C:40]=2[O:46][CH3:47])[CH:38]=1.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.CN1CCCN2CCCN=C12>C1(C)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:33][C:34]1[N:35]=[CH:36][N:37]([C:39]2[CH:45]=[CH:44][C:42]([NH:43][C:17]3[CH:31]=[C:20]4[CH2:21][CH2:22][CH:23]=[C:24]([C:25]5[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=5)[N:19]4[N:18]=3)=[CH:41][C:40]=2[O:46][CH3:47])[CH:38]=1

Participants

7

Reactant 4

HCID 1235837-Methyl-1,5,7-triazabicyclo[4.4.0]dec-5-eneHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 580757574-(4-chloro-1H-imidazol-1-yl)-3-methoxyanilineHCID 58110138HCID 58110138, compound

Product 1

HCID 66859615HCID 66859615, compoundYield 21%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Procedure

A mixture of 7-phenyl-4,5-dihydropyrazolo[1,5-a]pyridin-2-yl 1,1,2,2,3,3,4,4,4-nonafluorobutane-1-sulfonate (400 mg, 0.809 mmol, from AAH), 4-(4-chloro-1H-imidazol-1-yl)-3-methoxyaniline (362 mg, 1.618 mmol, from step 2 of preparation A), tris(dibenzylideneacetone)dipalladium(0) (29.6 mg, 0.032 mmol), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (70.2 mg, 0.121 mmol), and 1-methyl-2,3,4,6,7,8-hexahydro-1H-pyrimido[1,2-a]pyrimidine (372 mg, 2.428 mmol) in toluene (5 mL) was microwaved in a biotage chemistry microwave at 160° C. for 2 h. The crude reaction mixture was loaded directly on to silica gel and purified using silica gel column chromatography (0-80% EtOAc/hexanes) to afford N-(4-(4-chloro-1H-imidazol-1-yl)-3-methoxyphenyl)-7-phenyl-4,5-dihydropyrazolo[1,5-a]pyridin-2-amine (70 mg, 21% yield). LC-MS (M+H)+ 418.1. 1H NMR (500 MHz, chloroform-d) δ ppm 7.58 (dd, J=6.56, 1.37 Hz, 2 H) 7.49 (d, J=1.53 Hz, 1H) 7.43 (d, 0.1-2.44 Hz, 1 H) 7.34-7.40 (m, 3H) 7.02 (d, J=8.55 Hz, 1H) 6.99 (d, J=1.83 Hz, 1H) 6.53 (dd, J=8.55, 2.44 Hz, 1H) 6.31 (s, 1 H) 5.83 (s, 1 H) 5.47-5.52 (m, 1 H) 3.53 (s, 3 H) 2.96 (t, J=7.93 Hz, 2 H) 2.43-2.52 (m, 2H).

Workup

  1. customwas microwaved in a biotage chemistry microwave at 160° C. for 2 h
  2. customThe crude reaction mixture
  3. custompurified

Sources & evidence

ORD record
ord-9b651fe0408d4c37bb9b72fdecc1eada
Source dataset
uspto-grants-2013_01
Patent number
US08349880B2

Reaction notes

Loading…