Hexane → N-tert-Butyl-2-chloro-5-[(E)-2-ethoxyvinyl]pyrimidin-4-amine

HRID 82167

Reaction equation

HRID 82167 reaction equation
[B]1OC2C(=CC=CC=2)O1.[CH2:10]([O:12][C:13]#[CH:14])[CH3:11].CCCCCC.Br[C:22]1[C:23]([NH:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[N:24][C:25]([Cl:28])=[N:26][CH:27]=1.[OH-].[Na+]>C1COCC1.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.CCOC(C)=O>[C:30]([NH:29][C:23]1[C:22](/[CH:14]=[CH:13]/[O:12][CH2:10][CH3:11])=[CH:27][N:26]=[C:25]([Cl:28])[N:24]=1)([CH3:33])([CH3:31])[CH3:32]

Participants

9

Reactant 5

HCID 8058HexaneHCID 14798Sodium HydroxideHCID 61239Ether, ethyl ethynylHCID 6327445BenzcatechinboraneHCID 790766715-Bromo-N-tert-butyl-2-chloropyrimidin-4-amine

Product 1

HCID 86672092N-tert-Butyl-2-chloro-5-[(E)-2-ethoxyvinyl]pyrimidin-4-amineYield 55%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

Catecholborane (7.8 g, 65.4 mmol) in THF (50 mL) was added dropwise to a solution of 40% ethoxyacetylene in hexane (12.8 mL, 72.5 mmol) under nitrogen at 0-5° C. The mixture was stirred for 2 hours at room temperature then heated at 70° C. for 2 hours. The mixture was then cooled to room temperature and a solution of 5-bromo-N-tert-butyl-2-chloropyrimidin-4-amine (10 g, 37.8 mmol) (see Preparation 60) in THF (50 mL) was added. The solution was degassed with argon for about 25 minutes followed by the addition of Pd(PPh3)4 (1.3 g, 1.13 mmol) and powdered sodium hydroxide (4.53 g, 113 mmol). The mixture was heated at 70° C. for 16 hours and then cooled to room temperature. EtOAc (200 mL) was added and the mixture was filtered through a Celite™ pad. The filtrate was evaporated in vacuo and the residue was purified by column chromatography on silica gel (gradient of hexane:EtOAc 93:7 to 90:10) to afford the title compound as a yellow oil in 55% yield, 5.3 g.

Workup

  1. temperaturethen heated at 70° C. for 2 hours
  2. temperatureThe mixture was then cooled to room temperature
  3. customThe solution was degassed with argon for about 25 minutes
  4. temperatureThe mixture was heated at 70° C. for 16 hours
  5. temperaturecooled to room temperature
  6. filtrationthe mixture was filtered through a Celite™ pad
  7. customThe filtrate was evaporated in vacuo
  8. customthe residue was purified by column chromatography on silica gel (gradient of hexane:EtOAc 93:7 to 90:10)

Sources & evidence

ORD record
ord-4cf8f7e72045446fae6db9cdd0bd46ea
Source dataset
uspto-grants-2014_09
Patent number
US08846698B2

Linked notes

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