Hydrochloric Acid → HCID 131730311, compound

HRID 1948293Notes

Reaction equation

Cl[C:2]1[N:7]=[C:6]([C:8]([O:10]C)=[O:9])[CH:5]=[C:4]([N:12]2[CH2:17][CH2:16][C@H:15]([NH:18][C:19]([C:21]3[NH:22][C:23]([CH3:27])=[C:24]([Cl:26])[CH:25]=3)=[O:20])[C@H:14]([O:28][CH3:29])[CH2:13]2)[N:3]=1.[CH3:30][OH:31].Cl>C[O-].[Na+]>[Cl:26][C:24]1[CH:25]=[C:21]([C:19]([NH:18][C@H:15]2[CH2:16][CH2:17][N:12]([C:4]3[N:3]=[C:2]([O:31][CH3:30])[N:7]=[C:6]([C:8]([OH:10])=[O:9])[CH:5]=3)[CH2:13][C@H:14]2[O:28][CH3:29])=[O:20])[NH:22][C:23]=1[CH3:27]

Participants

Conditions

Temperature: 85 °C

Procedure

Cis(±)methyl 2-chloro-6-(4-{[(4-chloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-methoxypiperidin-1-yl)pyrimidine-4-carboxylate (Example 23; 0.12 g, 0.27 mmol) was dissolved in 0.5 M sodium methoxide in MeOH (5.4 ml, 2.7 mmol) and heated in the microwave for 1.5 h at 85° C. The reaction mixture was acidified with 1N HCl and the product was extracted with EtOAc, dried with MgSO4 and concentrated to a solid which was purified by reverse phase chromatography (gradient elution from 20-50% CH3CN in water with 0.5% TFA). Freeze drying yielded product as a white solid. MS (ES) MH+: 424 for C18H22ClN5O5; NMR: 1.62 (s, 1H), 1.75 (s, 1H), 2.14 (s, 3H), 3.26 (s, 3H), 3.53 (m, 3H), 3.87 (s, 3H), 4.22 (s, 2H), 6.88 (d, J=2.64 Hz, 1H), 7.07 (s, 1H), 7.66 (d, J=7.91 Hz, 1H), 11.63 (s, 1H).

Workup

extractionthe product was extracted with EtOAc
dry with materialdried with MgSO4
concentrationconcentrated to a solid which
customwas purified by reverse phase chromatography (gradient elution from 20-50% CH3CN in water with 0.5% TFA)
customFreeze drying
customyielded product as a white solid

Sources & evidence

ORD record: ord-fae88bad2f3648e5b6499ecb76e10142
Source dataset: uspto-grants-2013_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08399489B2

Reaction notes

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