Nitrogen → HCID 121331747, compound

HRID 64167Notes

Reaction equation

HRID 64167 reaction equation
Br[C:2]1[CH:3]=[C:4]([N:16]2[C:20]3[CH:21]=[CH:22][C:23]([C:25]4[CH:26]=[N:27][N:28]([CH3:30])[CH:29]=4)=[CH:24][C:19]=3[N:18]=[CH:17]2)[CH:5]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([F:14])=[CH:10][C:9]=2[F:15])[CH:7]=1.N#N.[N:33]1[CH:38]=[CH:37][CH:36]=[N:35][C:34]=1[NH2:39].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C([O-])([O-])=O.[Cs+].[Cs+]>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]>[F:15][C:9]1[CH:10]=[C:11]([F:14])[CH:12]=[CH:13][C:8]=1[C:6]1[CH:5]=[C:4]([N:16]2[C:20]3[CH:21]=[CH:22][C:23]([C:25]4[CH:26]=[N:27][N:28]([CH3:30])[CH:29]=4)=[CH:24][C:19]=3[N:18]=[CH:17]2)[CH:3]=[C:2]([NH:39][C:34]2[N:35]=[CH:36][CH:37]=[CH:38][N:33]=2)[CH:7]=1

Participants

8

Reactant 5

HCID 947NitrogenHCID 79782-AminopyrimidineHCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 895010831-(5-bromo-2',4'-difluoro-[1,1'-biphenyl]-3-yl)-5-(1-methyl-1H-pyrazol-4-yl)-1H-benzo[d]imidazole

Product 1

HCID 121331747HCID 121331747, compoundYield 11.6%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
110 °C

Procedure

A solution of 1-(5-bromo-2′,4′-difluoro-[1,1′-biphenyl]-3-yl)-5-(1-methyl-1H-pyrazol-4-yl)-1H-benzo[d]imidazole (0.075 g, 0.161 mmol) in 1,4-dioxane (3 ml) was degassed by N2 bubbling for 5 min. Pyrimidin-2-amine (0.018 g, 0.193 mmol, 1.2 eq.) was added and the mixture was degassed for another 5 min. Pd2(dba)3 (0.014 g, 0.016 mmol, 0.1 eq.) and xantphos (0.037 g, 0.064 mmol, 0.4 eq.) and Cs2CO3 (0.209 g, 0.644 mmol, 4.0 eq) were added sequentially and the mixture was further degassed for 5 min. and then heated at 110° C. for 16 h. The mixture was filtered on celite bed, quenched and extracted as in Example 1(d). The solvent was distilled off to afford the crude residue which was purified by column chromatography (60-120 silica gel, 2% methanol in ethyl acetate) to yield the title product in 11.6% yield (0.09 g). 1H NMR (400 MHz, DMSO-d6): δ 10.15 (s, 1H), 8.83 (S, 1H), 8.57-8.56 (D, 2H), 8.35 (s, 1H), 8.24 (s, 1H), 8.01-7.97 (s, 3H), 7.84-7.81 (d, 1H), 7.70-7.68 (m, 2H), 7.46-7.432 (m, 2H), 7.280-7.286 (m, 1H), 6.95-6.32 (t, 1H), 3.88 (s, 1H), LC-MS (ESI): Calculated mass: 479.48; Observed mass: 480.1 [M+H]+ (rt: 1.52 min).

Workup

  1. customthe mixture was degassed for another 5 min
  2. customthe mixture was further degassed for 5 min.
  3. filtrationThe mixture was filtered on celite bed
  4. customquenched
  5. extractionextracted as in Example 1(d)
  6. distillationThe solvent was distilled off
  7. customto afford the crude residue which
  8. customwas purified by column chromatography (60-120 silica gel, 2% methanol in ethyl acetate)

Sources & evidence

ORD record
ord-fea1297414664d5fb25b3f53bef96a1f
Source dataset
uspto-grants-2016_09
Patent number
US09447091B2

Reaction notes

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