Hydrochloric Acid → HCID 68749227, compound

HRID 624162Notes

Reaction equation

HRID 624162 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:13]3[CH:14]=[CH:15][CH:16]=[C:12]3[C:11](=[O:17])[NH:10][N:9]=2)=[CH:4][CH:3]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2[N:37](C)C)CCCCC1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].Cl.[OH-].[Na+]>C1(C)C=CC=CC=1.C1CCCCC1.C(OCC)(=O)C>[NH2:37][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:13]3[CH:14]=[CH:15][CH:16]=[C:12]3[C:11](=[O:17])[NH:10][N:9]=2)=[CH:4][CH:3]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 2733832Lithium HexamethyldisilazideHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 68752272HCID 68752272, compound

Product 1

HCID 68749227HCID 68749227, compound

Reagents, catalysts & solvents 2

HCID 1140TolueneSolvent2×HCID 21867204Cyclohexane ethylacetateSolvent

Procedure

To 1.181 g 4-(4-bromophenyl)pyrrolo[1,2-d][1,2,4]triazin-1(2H)-one (4.07 mmol) in toluene (10 ml) was added 0.080 g 2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl (0.2004 mmol), 0.063 g tris(dibenzylideneacetone)dipalladium(O) chloroform adduct (0.061 mmol) and 10.58 ml lithium bis(trimethylsilyl)amide 1M in toluene (10.58 mmol) under nitrogen at room temperature and the reaction was subsequently heated at 150° C. for 5 minutes by microwave (Biotage Initiator 2.5). Thin layer chromotography in cyclohexane/ethyl acetate=1/1 showed no starting material. After cooling the reaction mixture, 7 ml of 2N aqueous HCl was added, the mixture stirred for 30 minutes, and the mixture was basified until pH=10 by addition of aqueous NaOH (2N). A precipitate was formed. The solid was filtered and washed with ether and dried overnight to obtain the title compound. LCMS: m/z 227.0 (M+H). The filtrate was extracted with ethyl acetate. The organic phase was combined with the ether from the washing, dried over Na2SO4, filtered, and the solvent was evaporated under reduced pressure. The raw material was adsorbed on silica (dissolved in ethyl acetate), then purified by silica gel chromatography (cyclohexane:ethyl acetate gradient, the product was eluted at 80% of ethyl acetate) to afford additional title compound. 1H NMR (400 MHz, DMSO-d6) δ 11.85 (br. s., 1H), 7.32-7.44 (m, 3H), 7.09 (dd, J=3.8, 1.3 Hz, 1H), 6.66-6.77 (m, 3H), 5.67 (s, 2H). 13C NMR (400 MHz, DMSO-d6) δ 154.15, 150.86, 137.98, 129.55, 123.98, 118.70, 116.65, 113.95, 113.32, 110.58.

Workup

  1. additionwas added
  2. customA precipitate was formed
  3. filtrationThe solid was filtered
  4. washwashed with ether
  5. customdried overnight

Sources & evidence

ORD record
ord-01df03a8b3f147ecb51f03070091d94c
Source dataset
uspto-grants-2016_04
Patent number
US09302989B2

Reaction notes

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