Chloropyrazine → HCID 68184866, compound

HRID 2041711Notes

Reaction equation

HRID 2041711 reaction equation
Cl[C:2]1[CH:7]=[N:6][CH:5]=[CH:4][N:3]=1.CC([CH2:12][N:13]([CH2:17][CH2:18][N:19]1[CH:23]=[C:22]([C:24]2[CH:25]=[C:26]3[C:31](=[CH:32][CH:33]=2)[N:30]([C:34](=[O:36])[CH3:35])[C@@H:29]([CH3:37])[CH2:28][C@H:27]3[NH2:38])[CH:21]=[N:20]1)[C:14](=[O:16])[O-:15])(C)C.C1(P(C2CCCCC2)[C:46]2C=CC=[CH:48][C:47]=2[C:52]2C(N(C)C)=CC=CC=2)CCCCC1.CC(C)([O-])C.[Na+]>O1CCOCC1.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]>[C:34]([N:30]1[C:31]2[C:26](=[CH:25][C:24]([C:22]3[CH:21]=[N:20][N:19]([CH2:18][CH2:17][N:13]([CH3:12])[C:14](=[O:16])[O:15][C:47]([CH3:52])([CH3:48])[CH3:46])[CH:23]=3)=[CH:33][CH:32]=2)[C@H:27]([NH:38][C:2]2[CH:7]=[N:6][CH:5]=[CH:4][N:3]=2)[CH2:28][C@@H:29]1[CH3:37])(=[O:36])[CH3:35]

Participants

7

Reactant 4

HCID 73277ChloropyrazineHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 23676156Sodium t-butoxideHCID 86669444HCID 86669444, compound

Product 1

HCID 68184866HCID 68184866, compoundYield 56.9%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
110 °C

Procedure

A flask was charged with 2-chloropyrazine (138 mg, 1.209 mmol) and treated at room temperature under nitrogen with a solution of 1,1-dimethylethyl[2-(4-{(2S,4R)-1-acetyl-2-methyl-4-amino-1,2,3,4-tetrahydro-6-quinolinyl}-1H-pyrazol-1-yl)ethyl]methylcarbamate (for a preparation see intermediate 55) (250 mg, 0.605 mmol) in 1,4-dioxane (5 mL). 2′-(dicyclohexylphosphino)-N,N-dimethylbiphenyl-2-amine (DavePhos) (47.6 mg, 0.121 mmol), sodium tert-butoxide (116 mg, 1.209 mmol) and tris(dibenzylideneacetone)dipalladium(0) (55.4 mg, 0.060 mmol) were added and the resulting mixture was stirred under nitrogen at 110° C. for 16 h then cooled to room temperature and partitioned between EtOAc (25 mL) and water (25 mL). The layers were separated and the aqueous phase was extracted with EtOAc (25 mL). The combined organic phases were washed with brine (50 mL), dried over Na2SO4 and concentrated in vacuovacuo. Purification of this residue on SP4 using a 25 G silica cartridge (gradient:1 to 5% MeOH in DCM) gave 1,1-dimethylethyl (2-{4-[(2S,4R)-1-acetyl-2-methyl-4-(2-pyrazinylamino)-1,2,3,4-tetrahydro-6-quinolinyl]-1H-pyrazol-1-yl}ethyl)methylcarbamate (204.6 mg, 0.344 mmol, 56.9% yield) as an orange oil.

Workup

  1. temperaturethen cooled to room temperature
  2. custompartitioned between EtOAc (25 mL) and water (25 mL)
  3. customThe layers were separated
  4. extractionthe aqueous phase was extracted with EtOAc (25 mL)
  5. washThe combined organic phases were washed with brine (50 mL)
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated in vacuovacuo
  8. customPurification of this residue on SP4

Sources & evidence

ORD record
ord-24d197003492417f8185ac329da1e2c6
Source dataset
uspto-grants-2013_11
Patent number
US08580957B2

Reaction notes

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