2-Bromopyrimidine → HCID 67207801, compound

HRID 2041740Notes

Reaction equation

HRID 2041740 reaction equation
Cl.[C:2]([N:5]1[C:14]2[C:9](=[CH:10][C:11]([C:15]#[C:16][Si:17]([CH:24]([CH3:26])[CH3:25])([CH:21]([CH3:23])[CH3:22])[CH:18]([CH3:20])[CH3:19])=[CH:12][CH:13]=2)[C@H:8]([NH2:27])[CH2:7][C@@H:6]1[CH3:28])(=[O:4])[CH3:3].Br[C:30]1[N:35]=[CH:34][CH:33]=[CH:32][N:31]=1.CC(C)([O-])C.[Na+].CN(C)C1C=CC=CC=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1>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].C1(C)C=CC=CC=1>[C:2]([N:5]1[C:14]2[C:9](=[CH:10][C:11]([C:15]#[C:16][Si:17]([CH:21]([CH3:23])[CH3:22])([CH:18]([CH3:20])[CH3:19])[CH:24]([CH3:26])[CH3:25])=[CH:12][CH:13]=2)[C@H:8]([NH:27][C:30]2[N:35]=[CH:34][CH:33]=[CH:32][N:31]=2)[CH2:7][C@@H:6]1[CH3:28])(=[O:4])[CH3:3]

Participants

7

Reactant 4

HCID 783452-BromopyrimidineHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 23676156Sodium t-butoxideHCID 67205065HCID 67205065, compound

Product 1

HCID 67207801HCID 67207801, compoundYield 67.9%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

A flask was charged with (2S,4R)-1-acetyl-2-methyl-6-{[tris(1-methylethyl)silyl]ethynyl}-1,2,3,4-tetrahydro-4-quinolinamine hydrochloride (for a preparation see Intermediate 108) (295 mg, 0.7 mmol), 2-bromopyrimidine (334 mg, 2.100 mmol), sodium tert-butoxide (336 mg, 3.50 mmol), tris(dibenzylideneacetone)dipalladium(0) (641 mg, 0.700 mmol) and 2-(dimethylamino)-2′-(dicyclohexylphosphino)biphenyl (DavePhos) (551 mg, 1.400 mmol) then filled with toluene (10 mL) and the resulting mixture was stirred at 100° C. under nitrogen for 1.5 h then cooled to room temperature and partitioned between water and AcOEt, The two layers were filtered through celite then separated. The aqueous phase was extracted with AcOEt and the combined organic were washed with water then brine, dried over MgSO4 and concentrated in vacuo. Purification of the residue by SP4 using a 25 G silica cartridge (gradient:13 to 63% AcOEt in Hexanes) gave (2S,4R)-1-acetyl-2-methyl-N-2-pyrimidinyl-6-{[tris(1-methylethyl)silyl]ethynyl}-1,2,3,4-tetrahydro-4-quinolinamine (220 mg, 0.475 mmol, 67.9% yield) as a brown foam.

Workup

  1. temperaturethen cooled to room temperature
  2. custompartitioned between water and AcOEt
  3. filtrationThe two layers were filtered through celite
  4. customthen separated
  5. extractionThe aqueous phase was extracted with AcOEt
  6. washthe combined organic were washed with water
  7. dry with materialbrine, dried over MgSO4
  8. concentrationconcentrated in vacuo
  9. customPurification of the residue by SP4

Sources & evidence

ORD record
ord-39b81650651946a1b23f7560186db837
Source dataset
uspto-grants-2013_11
Patent number
US08580957B2

Reaction notes

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