Diisopropylethylamine → (6-Fluoro-4-oxo-3,4-dihydro-pyrido[2,3-d]pyrimidin-2-ylmethyl)-carbamic acid benzyl ester
Reaction equation
F[C:2]1[N:10]=[CH:9][C:8]([F:11])=[CH:7][C:3]=1[C:4]([OH:6])=O.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.CCN(C(C)C)C(C)C.[CH2:43]([O:50][C:51](=[O:57])[NH:52][CH2:53][C:54](=[NH:56])[NH2:55])[C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1>CN(C=O)C.ClCCl>[CH2:43]([O:50][C:51](=[O:57])[NH:52][CH2:53][C:54]1[NH:56][C:4](=[O:6])[C:3]2[CH:7]=[C:8]([F:11])[CH:9]=[N:10][C:2]=2[N:55]=1)[C:44]1[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- 90 °C
Procedure
2,5-Difluoronicotinic acid (547 mg, 3.44 mmol), TBTU (1.33 g, 4.14 mmol) and DIPEA (3.40 ml, 19.85 mmol) were added to a solution of carbamimidoylmethyl-carbamic acid benzyl ester [77390-81-9] (725 mg, 3.51 mmol) in DMF (20 ml). The solution was stirred for 5 hours at ambient temperature and 30 hours at 90° C. The brown suspension was poured onto ice cold aqueous buffer solution pH5/dichloromethane 1/1. The layers were separated, the aqueous layer was extracted twice with dichloromethane, the combined extracts were washed with brine and dried over magnesium sulfate. Removal of the solvent under reduced pressure and crystallization (EtOAc/TBME) yielded (6-fluoro-4-oxo-3,4-dihydro-pyrido[2,3-d]pyrimidin-2-ylmethyl)-carbamic acid benzyl ester (250 mg, 0.757 mmol; 22%) as white solid. MS: m/e=327.1 [M−H−].
Workup
- customThe layers were separated
- extractionthe aqueous layer was extracted twice with dichloromethane
- washthe combined extracts were washed with brine
- dry with materialdried over magnesium sulfate
- customRemoval of the solvent
- customunder reduced pressure and crystallization (EtOAc/TBME)
Sources & evidence
- ORD record
- ord-df511665f9934e72ace043c8266590db
- Source dataset
- uspto-grants-2009_08
- Patent number
- US07572801B2
Reaction notes
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