Sodium → HCID 21467991, compound
Reaction equation
[Na].[NH2:2][C:3]1[N:8]=[C:7]([NH2:9])[C:6](I)=[C:5]([CH3:11])[N:4]=1.[CH3:12][C:13]([C:20]1[CH:25]=[CH:24][C:23]([C:26]([F:29])([F:28])[F:27])=[CH:22][CH:21]=1)([CH3:19])/[CH:14]=[CH:15]/B(O)O>C(O)C>[NH2:2][C:3]1[N:8]=[C:7]([NH2:9])[C:6](/[CH:15]=[CH:14]/[C:13]([C:20]2[CH:21]=[CH:22][C:23]([C:26]([F:27])([F:29])[F:28])=[CH:24][CH:25]=2)([CH3:12])[CH3:19])=[C:5]([CH3:11])[N:4]=1Participants
Conditions
- Temperature
- 80 °C
Procedure
Sodium metal, 4.1 grams (0.18 mole), was stirred with 250 mL of ethanol for 30 minutes. After this time 20.0 grams (0.08 mole) of 2,4-diamino-5-iodo-6-methylpyrimidine (prepared in Step B of Example 3), 27.6 grams (0.11 mole) of trans-3-methyl-3-(4-trifluoromethylphenyl)-1-butenylboronic acid, and 9.2 grams (0.008 mole) of tetrakistriphenylphosphine palladium(0) were added. The reaction mixture was purged with nitrogen, and then heated to 80° C. where it stirred for about 28 hours. After this time the reaction mixture was concentrated under reduced pressure to about 20% of the original volume and then poured into 300 mL of water. The mixture was cooled in an ice-bath, and a solid was collected by filtration. The solid was triturated with a mixture of 1:1 petroleum ether:diethyl ether, and then subjected to column chromatography on silica gel using 5% methanol in methylene chloride as the eluant. The product-containing fractions were combined and concentrated under reduced pressure to a solid residue. The solid was recrystallized from 1-propanol and water, yielding 15.2 grams of trans-2,4-diamino-6-methyl-5-[3-(4-trifluoromethylphenyl)-3-methyl-1-butenyl]pyrimidine, mp 182°-185° C. The NMR spectrum was consistent with the proposed structure.
Workup
- customThe reaction mixture was purged with nitrogen
- concentrationAfter this time the reaction mixture was concentrated under reduced pressure to about 20% of the original volume
- additionpoured into 300 mL of water
- temperatureThe mixture was cooled in an ice-bath
- filtrationa solid was collected by filtration
- customThe solid was triturated with a mixture of 1:1 petroleum ether
- concentrationconcentrated under reduced pressure to a solid residue
- customThe solid was recrystallized from 1-propanol and water
Sources & evidence
- ORD record
- ord-70aa6cbdaa024f8fb5516b67c593101f
- Source dataset
- uspto-grants-1997_04
- Patent number
- US05622954
Reaction notes
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