Toluene → benzyl N-[2-[8-[(4-methoxyphenyl)methyl]-7-oxo-3,5,6,8,10-pentazatricyclo[7.4.0.02,6]trideca-1(9),2,4,10,12-pentaen-12-yl]ethyl]carbamate

HRID 926115

Reaction equation

HRID 926115 reaction equation
Br[C:2]1[CH:11]=[N:10][C:9]2[N:8]([CH2:12][C:13]3[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=3)[C:7](=[O:21])[N:6]3[N:22]=[CH:23][N:24]=[C:5]3[C:4]=2[CH:3]=1.[CH2:25]([O:32][C:33]([NH:35][CH2:36][CH2:37][B-](F)(F)F)=[O:34])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.[K+].C([O-])([O-])=O.[Cs+].[Cs+].C1(C)C=CC=CC=1>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl.O>[CH3:20][O:19][C:16]1[CH:17]=[CH:18][C:13]([CH2:12][N:8]2[C:9]3[N:10]=[CH:11][C:2]([CH2:37][CH2:36][NH:35][C:33](=[O:34])[O:32][CH2:25][C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)=[CH:3][C:4]=3[C:5]3=[N:24][CH:23]=[N:22][N:6]3[C:7]2=[O:21])=[CH:14][CH:15]=1

Participants

7

Reactant 4

HCID 1140TolueneHCID 10796Cesium carbonateHCID 49761741Potassium benzyl N-[2-(trifluoroboranuidyl)ethyl]carbamateHCID 867053859-bromo-6-(4-methoxybenzyl)pyrido[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one

Product 1

HCID 118116030benzyl N-[2-[8-[(4-methoxyphenyl)methyl]-7-oxo-3,5,6,8,10-pentazatricyclo[7.4.0.02,6]trideca-1(9),2,4,10,12-pentaen-12-yl]ethyl]carbamateYield 12%

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

9-Bromo-6-(4-methoxybenzyl)pyrido[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one (Example 1, 30 mg, 0.078 mol), potassium (2-(benzyloxycarbonylamino)ethyl)trifluoroborate (30 mg, 0.11 mol), Cs2CO3 (122 mg, 0.38 mmol), PdCl2(dppf)-DCM (5 mg, 0.01 mol), toluene (0.75 mL) and degassed water (0.25 mL) were added in order. The mixture was heated at 80° C. for 16 h, concentrated under a stream of nitrogen. The crude residue was taken up in DMF (1.5 mL), filtered and purified (HPLC, 0-85% ACN in water) to afford the title compound (6 mg, 12%) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ 2.92 (t, J=5.4 Hz, 2H), 3.35-3.36 (m, 2H), 3.69 (s, 3H), 4.94 (s, 2H), 5.58 (s, 2H), 6.83-6.85 (m, 2H), 7.24-7.26 (m, 2H), 7.35-7.37 (m, 2H), 7.40 (dd, J=4.4, 4.4 Hz, 1H), 8.51 (d, J=1.5 Hz, 1H), 8.61 (s, 1H), 8.65 (d, J=1.6 Hz, 1H). [M+H]=485.2.

Workup

  1. additionwere added in order
  2. concentrationconcentrated under a stream of nitrogen
  3. filtrationfiltered
  4. custompurified (HPLC, 0-85% ACN in water)

Sources & evidence

ORD record
ord-e8d25dd48e224324b79c3f086e5a05e7
Source dataset
uspto-grants-2016_03
Patent number
US09284335B2

Linked notes

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