Cesium carbonate → 1-(3,4-dihydroisoquinolin-2(1H)-yl)-3-((6-(1-methyl-1H-benzo[d]imidazol-6-yl)pyrazin-2-yl)amino)propan-2-ol

HRID 1399851Notes

Reaction equation

HRID 1399851 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][CH2:9][CH:10]([OH:22])[CH2:11][N:12]2[CH2:21][CH2:20][C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[CH2:13]2)[CH:5]=[N:4][CH:3]=1.[CH3:23][N:24]1[C:28]2[CH:29]=[C:30](B3OC(C)(C)C(C)(C)O3)[CH:31]=[CH:32][C:27]=2[N:26]=[CH:25]1.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.O>[CH2:13]1[C:14]2[C:19](=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH2:20][CH2:21][N:12]1[CH2:11][CH:10]([OH:22])[CH2:9][NH:8][C:6]1[CH:5]=[N:4][CH:3]=[C:2]([C:30]2[CH:31]=[CH:32][C:27]3[N:26]=[CH:25][N:24]([CH3:23])[C:28]=3[CH:29]=2)[N:7]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 594746911-Methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-YL)-1H-benzo[D]imidazoleHCID 718625141-((6-chloropyrazin-2-yl)amino)-3-(3,4-dihydroisoquinolin-2(1H)-yl)propan-2-ol

Product 1

HCID 867292591-(3,4-dihydroisoquinolin-2(1H)-yl)-3-((6-(1-methyl-1H-benzo[d]imidazol-6-yl)pyrazin-2-yl)amino)propan-2-olYield 13%

Reagents, catalysts & solvents 1

HCID 218864351,4-Dioxane--water (1/1)Solvent

Procedure

To a flask containing 1-((6-chloropyrazin-2-yl)amino)-3-(3,4-dihydroisoquinolin-2(1H)-yl)propan-2-ol (200 mg, 0.6 mmol) in dioxane:H2O (3:1) was added 1-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-benzo[d]imidazole (200 mg, 0.8 mmol), Cs2CO3 (2 equiv.) and Pd(dppfCl2) (10 mol %). The mixture was degassed 3 times with N2 before being heated at 110 deg C. overnight. Upon completion, the solvents were evaporated and residue purified with prep-HPLC to afford the desired target compound (32 mg, yield 13%). 1H NMR (400 MHz, MeOD): δ 8.27 (s, 1H), 8.18 (d, J=9.6 Hz, 2H), 7.99 (d, J=8.8 Hz, 1H), 7.86 (s, 1H), 7.72 (d, J=8.4 Hz, 1H), 7.09-6.99 (m, 3H), 6.87 (d, J=7.6 Hz, 1H), 4.21 (br.s, 1H), 3.86 (s, 3H), 3.84-3.54 (m, 4H), 2.89-2.66 (m, 6H). LCMS (m/z): 415.2 (M+1).

Workup

  1. customThe mixture was degassed 3 times with N2
  2. temperaturebefore being heated at 110 deg C
  3. customovernight
  4. customUpon completion, the solvents were evaporated
  5. customresidue purified with prep-HPLC

Sources & evidence

ORD record
ord-4eb760d3b5fb4b48aa44aa4645e56e58
Source dataset
uspto-grants-2014_12
Patent number
US08906900B2

Reaction notes

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