Diethyl cyanophosphonate → HCID 71526223, compound
Reaction equation
[CH:1]1([C:4]2[N:5]=[CH:6][C:7]([C:15]([OH:17])=O)=[N:8][C:9]=2[O:10][CH2:11][CH:12]2[CH2:14][CH2:13]2)[CH2:3][CH2:2]1.C(OP(C#N)(OCC)=O)C.CCN(C(C)C)C(C)C.[CH:37]1([CH2:40][C@H:41]([NH2:48])[C:42]2[N:46]=[C:45]([CH3:47])[O:44][N:43]=2)[CH2:39][CH2:38]1>COCCOC>[CH:37]1([CH2:40][C@H:41]([NH:48][C:15]([C:7]2[CH:6]=[N:5][C:4]([CH:1]3[CH2:2][CH2:3]3)=[C:9]([O:10][CH2:11][CH:12]3[CH2:13][CH2:14]3)[N:8]=2)=[O:17])[C:42]2[N:46]=[C:45]([CH3:47])[O:44][N:43]=2)[CH2:39][CH2:38]1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 100 °C
Procedure
5-Cyclopropyl-6-cyclopropylmethoxy-pyrazine-2-carboxylic acid (Example 10 g, 100 mg, 0.43 mmol) was suspended in DME (3 mL). Diethoxy-phosphorylformonitrile (226.0 mg, 0.80 mmol), DIEA (0.63 mL, 4.2 mmol) and (S)-2-cyclopropyl-1-(5-methyl-[1, 2, 4]oxadiazol-3-yl)-ethylamine (Example 20e, 82.2 mg, 0.64 mmol) were added and the reaction mixture was heated at 100° C. for 10 min under microwave condition. The mixture was extracted with ethyl acetate and water; the organic phase was dried over Na2SO4, filtered and concentrated in vacuo. The crude material was purified by reverse phase preparative HPLC (Xterra-RP18, 10 μ, 19×250 mm/acetonitrile/10 mM ammonium acetate in water) to give the desired product (20 mg, 11.72%) as white solid; LC-MS (UV peak area, ESI) 96.20%, 384.2 (M+H).
Workup
- extractionThe mixture was extracted with ethyl acetate and water
- dry with materialthe organic phase was dried over Na2SO4
- filtrationfiltered
- concentrationconcentrated in vacuo
- customThe crude material was purified by reverse phase preparative HPLC (Xterra-RP18, 10 μ, 19×250 mm/acetonitrile/10 mM ammonium acetate in water)
Sources & evidence
- ORD record
- ord-d8e1ef96ca2a4dadab8eec4388af206b
- Source dataset
- uspto-grants-2016_08
- Patent number
- US09403808B2
Reaction notes
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