Dimethylformamide → HCID 18504799, compound
Reaction equation
[Cl:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Cl:9])[C:7]=1[CH3:8].[H-].[Na+].Cl[C:13]1[C:22]2[C:17](=[C:18]([O:27][CH:28]3[CH2:32][CH2:31]CO3)[C:19]([O:23][CH:24]([F:26])[F:25])=[CH:20][CH:21]=2)[CH:16]=[N:15][N:14]=1.CN([CH:36]=[O:37])C>>[Cl:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Cl:9])[C:7]=1[CH2:8][C:13]1[C:22]2[C:17](=[C:18]([O:27][CH:28]3[CH2:32][CH2:31][O:37][CH2:36]3)[C:19]([O:23][CH:24]([F:25])[F:26])=[CH:20][CH:21]=2)[CH:16]=[N:15][N:14]=1Participants
Procedure
A solution under nitrogen of 3,5-dichloro-4-methyl-pyridine (457 mg, 2.82 mmoles) in dry DMF (10 ml) was portionwise added with 60% NaH (113 mg, 2.82 mmoles) and, after 1 hour at room temperature, was dropwise added, at a temperature <10° C., with 1-chloro-6-difluoromethoxy-5-(tetrahydrofuran-2-yloxy)-phthalazine (296 mg, 0.937 mmoles), obtained as described in example 53, in dry DMF (10 ml). After 2 hours at room temperature the mixture was poured into a 0.4M buffer at pH=7 (50 ml), extracted in ethyl acetate (2×50 ml) and the organic phase was washed with water, anhydrified and concentrated under vacuum. The residue was chromatographed (eluent:benzene/ethyl acetate 1:1, then ethyl acetate only), then crystallized from ethyl ether/benzene to give 180 mg of the title product (yield: 43.5%).
Workup
- customobtained
- additionAfter 2 hours at room temperature the mixture was poured into a 0.4M buffer at pH=7 (50 ml)
- extractionextracted in ethyl acetate (2×50 ml)
- washthe organic phase was washed with water, anhydrified
- concentrationconcentrated under vacuum
- customThe residue was chromatographed (eluent
- custombenzene/ethyl acetate 1:1, then ethyl acetate only), then crystallized from ethyl ether/benzene
Sources & evidence
- ORD record
- ord-c0b5395a4bae45f3a6c6a91d626cf67a
- Source dataset
- uspto-grants-2003_07
- Patent number
- US06589951B1
Reaction notes
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