Hydrazinecarboxylic acid, ethyl ester → HCID 136596980, compound

HRID 1476850Notes

Reaction equation

[C:1]([C:3]1[N:4]=[C:5]([CH2:13][O:14][C@H:15]2[CH2:19][CH2:18][N:17](C(OC(C)(C)C)=O)[CH2:16]2)[C:6]2[C:11]([CH:12]=1)=[CH:10][CH:9]=[CH:8][CH:7]=2)#[N:2].[NH:27]([C:29](OCC)=[O:30])[NH2:28].C1CCN2C(=NCCC2)CC1>CN1C(=O)CCC1>[NH:17]1[CH2:18][CH2:19][C@H:15]([O:14][CH2:13][C:5]2[C:6]3[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=3)[CH:12]=[C:3]([C:1]3[NH:2][C:29](=[O:30])[NH:27][N:28]=3)[N:4]=2)[CH2:16]1

Participants

Conditions

Temperature: 170 °C

Procedure

A mixture of (S)-tert-butyl 3-((3-cyanoisoquinolin-1-yl)methoxy)pyrrolidine-1-carboxylate (54.6 mg, 0.154 mmol) in NMP (0.4 mL), ethyl hydrazinecarboxylate (80 mg, 0.772 mmol) and DBU (0.012 mL, 0.077 mmol) was heated at 170° C. overnight and then filtered. The product in the filtrate was purified by mass-triggered HPLC eluting with a gradient of 35-60% ACN in water (acid mode). The product-containing fractions were concentrated in vacuo, treated with neat TFA (1 mL) for 5 minutes, and again concentrated in vacuo. The concentrate was dispersed in ACN/water (1:1) and lyophilized to give the title compound (7.5 mg, 16%). ESI-MS m/z [M+H]+ 312.6.

Workup

filtrationfiltered
customThe product in the filtrate was purified by mass-triggered HPLC
washeluting with a gradient of 35-60% ACN in water (acid mode)
concentrationThe product-containing fractions were concentrated in vacuo
additiontreated with neat TFA (1 mL) for 5 minutes
concentrationagain concentrated in vacuo
additionThe concentrate was dispersed in ACN/water (1:1)

Sources & evidence

ORD record: ord-93a2536d483248e78eb2382affbac8a8
Source dataset: uspto-grants-2016_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09402841B2

Reaction notes

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