2-Bromopyrimidine → HCID 68184865, compound

HRID 2041712Notes

Reaction equation

HRID 2041712 reaction equation
[C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10]([C:14]3[CH:15]=[N:16][N:17]([CH2:19][CH2:20][N:21]([CH3:29])[C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])[CH:18]=3)=[CH:11][CH:12]=2)[C@H:7]([NH2:30])[CH2:6][C@@H:5]1[CH3:31])(=[O:3])[CH3:2].Br[C:33]1[N:38]=[CH:37][CH:36]=[CH:35][N:34]=1.CC(C)([O-])C.[Na+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(N(C)C)=CC=CC=2)CCCCC1>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].O1CCOCC1>[C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10]([C:14]3[CH:15]=[N:16][N:17]([CH2:19][CH2:20][N:21]([CH3:29])[C:22](=[O:28])[O:23][C:24]([CH3:25])([CH3:26])[CH3:27])[CH:18]=3)=[CH:11][CH:12]=2)[C@H:7]([NH:30][C:33]2[N:38]=[CH:37][CH:36]=[CH:35][N:34]=2)[CH2:6][C@@H:5]1[CH3:31])(=[O:3])[CH3:2]

Participants

7

Reactant 4

HCID 783452-BromopyrimidineHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 23676156Sodium t-butoxideHCID 68162631HCID 68162631, compound

Product 1

HCID 68184865HCID 68184865, compoundYield 20.85%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
110 °C

Procedure

A flask was charged with 1,1-dimethylethyl (2-{4-[(2S,4R)-1-acetyl-4-amino-2-methyl-1,2,3,4-tetrahydro-6-quinolinyl]-1H-pyrazol-1-yl}ethyl)methylcarbamate (for a preparation see intermediate 55) (250 mg, 0.585 mmol), 2-bromopyrimidine (186 mg, 1.169 mmol), sodium tert-butoxide (112 mg, 1.169 mmol), 2′-(dicyclohexylphosphino)-N,N-dimethylbiphenyl-2-amine (DavePhos) (46.0 mg, 0.117 mmol) and then tris(dibenzylideneacetone)dipalladium(0) (53.5 mg, 0.058 mmol) then filled with 1,4-dioxane (5 mL) and the resulting mixture was stirred 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 50 G silica cartridge (gradient:1 to 5% MeOH in DCM) gave 1,1-dimethylethyl (2-{4-[(2S,4R)-1-acetyl-2-methyl-4-(2-pyrimidinylamino)-1,2,3,4-tetrahydro-6-quinolinyl]-1H-pyrazol-1-yl}ethyl)methylcarbamate (68.5 mg, 0.122 mmol, 20.85% 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-d67e81b04ef740989445e4e54572ccb5
Source dataset
uspto-grants-2013_11
Patent number
US08580957B2

Reaction notes

Loading…