Hydrazinecarboxylic acid, ethyl ester → (S)-tert-butyl 3-((6-(5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)-1,7-naphthyridin-8-yl)amino)pyrrolidine-1-carboxylate

HRID 1476860Notes

Reaction equation

[C:1]([C:3]1[CH:4]=[C:5]2[C:10](=[C:11]([NH:13][C@H:14]3[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15]3)[N:12]=1)[N:9]=[CH:8][CH:7]=[CH:6]2)#[N:2].[NH:26]([C:28](OCC)=[O:29])[NH2:27]>CN1C(=O)CCC1.CCOC(C)=O>[O:29]=[C:28]1[NH:26][N:27]=[C:1]([C:3]2[CH:4]=[C:5]3[C:10](=[C:11]([NH:13][C@H:14]4[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15]4)[N:12]=2)[N:9]=[CH:8][CH:7]=[CH:6]3)[NH:2]1

Participants

Conditions

Temperature: 175 °C

Procedure

To (S)-tert-butyl 3-((6-cyano-1,7-naphthyridin-8-yl)amino)pyrrolidine-1-carboxylate (210 mg, 0.619 mmol) in NMP (1.5 mL) was added ethyl hydrazinecarboxylate (258 mg, 2.475 mmol). The reaction mixture was heated at 175° C. for 2 days and was then cooled, diluted with EtOAc, and washed with aqueous NH4Cl. The organic phase was dried and concentrated. The crude product was purified by preparative HPLC eluting with a gradient of 35-60% ACN in water (acid mode) to give the title compound (80 mg, 33%).

Workup

temperaturewas then cooled
washwashed with aqueous NH4Cl
customThe organic phase was dried
concentrationconcentrated
customThe crude product was purified by preparative HPLC
washeluting with a gradient of 35-60% ACN in water (acid mode)

Sources & evidence

ORD record: ord-0a447ab3a95c429b933db8f0147e9c7c
Source dataset: uspto-grants-2016_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09402841B2

Reaction notes

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