Cesium carbonate → (2-{4,4-Dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}-4-{6-methoxy-5-[(2-methylpyrimidin-4-yl)amino]pyridin-3-yl}pyridin-3-yl)methyl Acetate

HRID 1021979Notes

Reaction equation

HRID 1021979 reaction equation
Cl[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:16]=[CH:15][N:14]=[C:13]([CH3:17])[N:12]=2)[C:5]([O:8][CH3:9])=[N:6][CH:7]=1.[C:18]([O:21][CH2:22][C:23]1[C:24]([N:32]2[CH2:43][CH2:42][N:41]3[C:34](=[CH:35][C:36]4[CH2:37][C:38]([CH3:45])([CH3:44])[CH2:39][C:40]=43)[C:33]2=[O:46])=[N:25][CH:26]=[CH:27][C:28]=1B(O)O)(=[O:20])[CH3:19].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.C([O-])([O-])=O.[Cs+].[Cs+]>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].O.O1CCOCC1>[C:18]([O:21][CH2:22][C:23]1[C:24]([N:32]2[CH2:43][CH2:42][N:41]3[C:34](=[CH:35][C:36]4[CH2:37][C:38]([CH3:45])([CH3:44])[CH2:39][C:40]=43)[C:33]2=[O:46])=[N:25][CH:26]=[CH:27][C:28]=1[C:2]1[CH:7]=[N:6][C:5]([O:8][CH3:9])=[C:4]([NH:10][C:11]2[CH:16]=[CH:15][N:14]=[C:13]([CH3:17])[N:12]=2)[CH:3]=1)(=[O:20])[CH3:19]

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 75806TricyclohexylphosphineHCID 86684340[4-(Dihydroxyboranyl)-2-{4,4-dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}pyridin-3-yl]methyl acetateHCID 86684411N-(5-Chloro-2-methoxypyridin-3-yl)-2-methylpyrimidin-4-amine

Product 1

HCID 86684412(2-{4,4-Dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}-4-{6-methoxy-5-[(2-methylpyrimidin-4-yl)amino]pyridin-3-yl}pyridin-3-yl)methyl AcetateYield 25%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

A sealed tube equipped with a magnetic stirrer was charged with 222a (550 mg, 2.2 mmol), (3-(acetoxymethyl)-2-(7,7-dimethyl-1-oxo-3,4,7,8-tetrahydro-1H-cyclopenta[4,5]pyrrolo-[1,2-a]pyrazin-2(6H)-yl)pyridin-4-yl)boronic acid 199e (2.18 g, 5.5 mmol), Pd2(dba)3 (201 mg, 0.22 mmol), tricyclohexylphospine (84 mg, 0.30 mmol), Cs2CO3 (1.43 g, 4.4 mmol), dioxane (12 mL), and water (1 mL). After three cycles of vacuum/argon flush, the mixture was heated at 110° C. for 4 h. It was then filtered and the filtrate was evaporated in vacuo. The residue was purified by silica-gel column chromatography eluting with 30:1 ethyl acetate/methanol to afford 222b (310 mg, 25%) as a yellow solid. MS-ESI: [M+H]+ 568.6

Workup

  1. customA sealed tube equipped with a magnetic stirrer
  2. customAfter three cycles of vacuum/argon flush
  3. filtrationIt was then filtered
  4. customthe filtrate was evaporated in vacuo
  5. customThe residue was purified by silica-gel column chromatography
  6. washeluting with 30:1 ethyl acetate/methanol

Sources & evidence

ORD record
ord-187a6a5b96954263951ed6a677b5bbef
Source dataset
uspto-grants-2014_05
Patent number
US08716274B2

Reaction notes

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