Cesium carbonate → (R)-2,2-difluoro-1-(2-((7-(4-(4-methylpiperazin-1-yl)phenyl)pyrido[4,3-b]pyrazin-5-ylamino)methyl)morpholino)ethanone

HRID 57633Notes

Reaction equation

HRID 57633 reaction equation
Cl[C:2]1[N:11]=[C:10]([NH:12][CH2:13][C@@H:14]2[CH2:19][N:18]([C:20](=[O:24])[CH:21]([F:23])[F:22])[CH2:17][CH2:16][O:15]2)[C:9]2[C:4](=[N:5][CH:6]=[CH:7][N:8]=2)[CH:3]=1.C([O-])([O-])=O.[Cs+].[Cs+].[CH3:31][N:32]1[CH2:37][CH2:36][N:35]([C:38]2[CH:43]=[CH:42][C:41](B3OC(C)(C)C(C)(C)O3)=[CH:40][CH:39]=2)[CH2:34][CH2:33]1>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:22][CH:21]([F:23])[C:20]([N:18]1[CH2:17][CH2:16][O:15][C@H:14]([CH2:13][NH:12][C:10]2[C:9]3[C:4](=[N:5][CH:6]=[CH:7][N:8]=3)[CH:3]=[C:2]([C:41]3[CH:40]=[CH:39][C:38]([N:35]4[CH2:36][CH2:37][N:32]([CH3:31])[CH2:33][CH2:34]4)=[CH:43][CH:42]=3)[N:11]=2)[CH2:19]1)=[O:24]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 179989051-Methyl-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperazineHCID 86717395(R)-1-(2-((7-chloropyrido[4,3-b]pyrazin-5-ylamino)methyl)morpholino)-2,2-difluoroethanone

Product 1

HCID 86717394(R)-2,2-difluoro-1-(2-((7-(4-(4-methylpiperazin-1-yl)phenyl)pyrido[4,3-b]pyrazin-5-ylamino)methyl)morpholino)ethanone

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
110 °C

Procedure

To a solution of (R)-1-(2-((7-chloropyrido[4,3-b]pyrazin-5-ylamino)methyl)morpholino)-2,2-difluoroethanone (72 mg, 0.2 mmol) in dioxane/H2O (5 mL/0.5 mL) was added Cs2CO3 (98 mg, 0.3 mmol), Pd (PPh3)4 (46.2 mg, 0.04 mmol) and 1-methyl-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperazine (72.5 mg, 0.24 mmol). The mixture was stirred at 110° C. for 24 hours under N2. The reaction was filtered, concentrated and purified on column (CH2Cl2:MeOH=20:1) to give yellow solid. MS (m/z): 498 (M+H)+

Workup

  1. filtrationThe reaction was filtered
  2. concentrationconcentrated
  3. custompurified on column (CH2Cl2:MeOH=20:1)
  4. customto give yellow solid

Sources & evidence

ORD record
ord-2759147125e54f289dbc273ee2fcfefc
Source dataset
uspto-grants-2016_09
Patent number
US09434726B2

Reaction notes

Loading…