(3S)-(-)-3-(tert-Butoxycarbonylamino)pyrrolidine → HCID 10266316, compound

HRID 1696901Notes

Reaction equation

Cl[C:2]1[N:11]=[C:10]2[C:5]([C:6](=[O:21])[C:7]([C:16]([O:18]CC)=[O:17])=[CH:8][N:9]2CCC#N)=[CH:4][C:3]=1[F:22].C(OC([NH:30][C@H:31]1[CH2:35][CH2:34][NH:33][CH2:32]1)=O)(C)(C)C>C(#N)C>[NH2:30][C@H:31]1[CH2:35][CH2:34][N:33]([C:2]2[N:11]=[C:10]3[C:5]([C:6](=[O:21])[C:7]([C:16]([OH:18])=[O:17])=[CH:8][NH:9]3)=[CH:4][C:3]=2[F:22])[CH2:32]1

Participants

Conditions

Temperature: 80 °C

Procedure

A solution of Example 7C (32.4 mg) and (3S)-3-(tert-butoxycarbonylamino)pyrrolidine (55.8 mg) in acetonitrile (1 mL) in a sealed vial was heated for 24 hours then cooled and concentrated. The concentrate was dissolved in 1:1 DMSO/methanol (1 mL) and chromatographed by reverse phase HPLC. The product was suspended in 2-propanol (1 mL), treated with 1M LiOH (1.2 mL), heated at 80° C. for 18 hours in a sealed vial for 24 hours, and concentrated. The concentrate was treated with 10% citric acid to pH 4-6 and filtered. The filtrant was dissolved in 4M HCl/dioxane (1.5 mL), and this solution was stirred for 2 hours and concentrated. NMR (500 MHz DMSO-d6) δ 13.4 (m, 1H), 8.50 (m, 1H), 8.45 (s, 2H), 8.00 (m, 1H), 4.00-3.40 (m, 5H), 2.38 (m, 1H), 2.18 (m, 1H).

Workup

temperaturethen cooled
concentrationconcentrated
dissolutionThe concentrate was dissolved in 1:1 DMSO/methanol (1 mL)
customchromatographed by reverse phase HPLC
additiontreated with 1M LiOH (1.2 mL)
concentrationconcentrated
additionThe concentrate was treated with 10% citric acid to pH 4-6
filtrationfiltered
dissolutionThe filtrant was dissolved in 4M HCl/dioxane (1.5 mL)
concentrationconcentrated

Sources & evidence

ORD record: ord-e843e8f937b743d690169773a5fdcee0
Source dataset: uspto-grants-2012_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08163769B2

Reaction notes

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