2-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenyl → 6-({2-[(3,5-Dimethylphenyl)amino][1,2,4]triazolo[1,5-a]pyrazin-8-yl}amino)-2,2-difluoro-2H-1,4-benzoxazin-3(4H)-one

HRID 570607Notes

Reaction equation

HRID 570607 reaction equation
Cl[C:2]1[C:3]2[N:4]([N:8]=[C:9]([NH:11][C:12]3[CH:17]=[C:16]([CH3:18])[CH:15]=[C:14]([CH3:19])[CH:13]=3)[N:10]=2)[CH:5]=[CH:6][N:7]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2N(C)C)CCCCC1.[NH2:48][C:49]1[CH:50]=[CH:51][C:52]2[O:57][C:56]([F:59])([F:58])[C:55](=[O:60])[NH:54][C:53]=2[CH:61]=1>O1CCOCC1.O1CCCC1.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]>[CH3:19][C:14]1[CH:13]=[C:12]([NH:11][C:9]2[N:10]=[C:3]3[C:2]([NH:48][C:49]4[CH:50]=[CH:51][C:52]5[O:57][C:56]([F:59])([F:58])[C:55](=[O:60])[NH:54][C:53]=5[CH:61]=4)=[N:7][CH:6]=[CH:5][N:4]3[N:8]=2)[CH:17]=[C:16]([CH3:18])[CH:15]=1

Participants

7

Reactant 3

HCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 22061146HCID 22061146, compoundHCID 866943458-Chloro-[1,2,4]triazolo[1,5-a]pyrazin-2-yl-(3,5-dimethyl-phenyl)-amine

Product 1

HCID 665838436-({2-[(3,5-Dimethylphenyl)amino][1,2,4]triazolo[1,5-a]pyrazin-8-yl}amino)-2,2-difluoro-2H-1,4-benzoxazin-3(4H)-one

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8028TetrahydrofuranSolventHCID 312751,4-DioxaneSolvent

Procedure

8-Chloro-[1,2,4]triazolo[1,5-a]pyrazin-2-yl-(3,5-dimethyl-phenyl)-amine (0.075 g, 0.2 mmol), tris(dibenzylideneacetone)dipalladium(0) (0.01 g, 0.01 mmol), 2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl (0.01 g, 0.02 mmol) and 6-amino-2,2-difluoro-2H-1,4-benzoxazin-3(4H)-one (0.049 g, 0.2 mmol) are taken in dry 1,4 dioxane (2 mL). Sodiumhexamethyldiisilylamide (1 M in tetrahydrofuran) (0.27 mL, 0.2 mmol) is added and the reaction irradiated in the microwave at 150° C. for 30 minutes. The reaction mixture is quenched with dry methanol (1 mL) and passed through a celite pad. The filtrate is concentrated and purified by flash column chromatography using Silica gel (230-400) mesh to get the titled product as an off white solid (10 mg, 10.4%). TLC: pet ether/ethylacetate (6/4) Rf-0.4. LCMS (method A): mass found (M+H+, 438), Rt (min): 5.11 area % 93.7 (max), 94.4 (254 nm); 1H NMR (400 MHz, DMSO-d6): δ [ppm] 11.99 (s, 1H), 9.63 (s, 1H), 9.39 (s, 1H), 8.27 (d, J=4.48 Hz, 1H), 7.93 (d, J=2.44 Hz, 1H), 7.63 (m, 1H), 7.57 (d, J=4.48 Hz, 1H), 7.35 (s, 2H), 7.27 (d, J=8.92 Hz, 1H), 6.55 (s, 1H), 2.25 (s, 6H).

Workup

  1. customthe reaction irradiated in the microwave at 150° C. for 30 minutes
  2. customThe reaction mixture is quenched with dry methanol (1 mL)
  3. concentrationThe filtrate is concentrated
  4. custompurified by flash column chromatography

Sources & evidence

ORD record
ord-0bb9ca7c761e43c5a086c5ca5e902f0f
Source dataset
uspto-grants-2015_05
Patent number
US09023851B2

Reaction notes

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