HCID 58902037, compound → HCID 58901999, compound

HRID 1992422Notes

Reaction equation

[CH2:1]([O:3][C:4](=[O:30])[C:5]([NH:7][CH:8]([C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([O:22][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH:17]=1)[C:9]1[C:14]([Cl:15])=[N:13][CH:12]=[CH:11][N:10]=1)=O)[CH3:2]>O=P(Cl)(Cl)Cl.CN(C=O)C>[CH2:1]([O:3][C:4]([C:5]1[N:10]2[CH:11]=[CH:12][N:13]=[C:14]([Cl:15])[C:9]2=[C:8]([C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([O:22][CH2:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[CH:17]=2)[N:7]=1)=[O:30])[CH3:2]

Participants

Conditions

Temperature: 75 °C

Procedure

A solution of N-[(3-benzyloxy-phenyl)-(3-chloro-pyrazin-2-yl)-methyl]-oxalamic acid ethyl ester (50 mg, 0.12 mmol) in POCl3 (2 mL) was heated to 55° C. for 17.5 h. Very little reaction occurred therefore DMF (3 drops) was added to reaction mixture and heated to 75° C. overnight. The brown reaction mixture was allowed to cool to rt, concentrated in vacuo and then quenched with 2M NH3 in i-PrOH at 0° C. until the pH was basic. The reaction mixture was concentrated in vacuo and the crude material was purified by chromatography on silica gel [eluting with 2% EtOAc in DCM], resulting in the title compound as an off-white solid; 1H NMR (CDCl3, 400 MHz) δ 1.48 (t, J=7.2 Hz, 3H), 4.56 (q, J=7.2 Hz, 2H), 5.13 (s, 2H), 7.05-7.09 (m, 1H), 7.22-7.29 (m, 2H), 7.29-7.47 (m, 6H), 7.67 (d, J=5.2 Hz, 1H), 9.15 (d, J=5.2 Hz, 1H); MS (ES+): m/z=408.07 (100) [MH+], HPLC: tR=3.88 min (MicromassZQ, polar—5 min).

Workup

customVery little reaction
temperatureto cool to rt
concentrationconcentrated in vacuo
customquenched with 2M NH3 in i-PrOH at 0° C. until the pH
concentrationThe reaction mixture was concentrated in vacuo
customthe crude material was purified by chromatography on silica gel [eluting with 2% EtOAc in DCM]

Sources & evidence

ORD record: ord-a23b922f896e4842baf13257215559d7
Source dataset: uspto-grants-2010_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07648987B2

Reaction notes

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