Sodium Hydroxide → HCID 178524766, compound

HRID 707365Notes

Reaction equation

[CH:1]1([N:4]2[C:12]3[C:7](=[N:8][CH:9]=[CH:10][N:11]=3)[N:6]([C@H:13]3[CH2:16][C@H:15]([NH:17][C:18]4[S:19][C:20]([C:23]([O:25]C)=[O:24])=[CH:21][N:22]=4)[CH2:14]3)[C:5]2=[O:27])[CH2:3][CH2:2]1.[OH-].[Na+]>C(O)C>[CH:1]1([N:4]2[C:12]3[C:7](=[N:8][CH:9]=[CH:10][N:11]=3)[N:6]([C@H:13]3[CH2:16][C@H:15]([NH:17][C:18]4[S:19][C:20]([C:23]([OH:25])=[O:24])=[CH:21][N:22]=4)[CH2:14]3)[C:5]2=[O:27])[CH2:2][CH2:3]1

Participants

Conditions

Temperature: 80 °C

Procedure

To a suspension of methyl 2-((trans-3-(3-cyclopropyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyrazin-1-yl)cyclobutyl)amino)thiazole-5-carboxylate, (EXAMPLE 148), (0.35 g, 0.906 mmol) in ethanol (5 mL) was added sodium hydroxide 1.0 N solution (2.72 mL, 2.72 mmol). The reaction mixture was heated to 80° C. for 1 h and concentrated. The residue was diluted with water and the pH of the resulting solution adjusted to 6 by the addition of 1N HCl (3.1 mL) solution. The precipitate formed was filtered and dried under high vacuum to give the title compound 2-((trans-3-(3-cyclopropyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyrazin-1-yl)cyclobutyl)amino)thiazole-5-carboxylic acid (0.300 g, 0.806 mmol, 89% yield). m/z: 373.0 (M+1); 1H NMR (400 MHz, DMSO-d6) δ: ppm 12.50 (br. s., 1 H), 8.18-8.51 (m, 1 H), 7.79-8.15 (m, 2 H), 7.35-7.66 (m, 1 H), 5.14 (quin, J=8.26 Hz, 1 H), 4.38 (br. s., 1 H), 3.16-3.31 (m, 2 H), 2.97 (tt, J=7.02, 3.64 Hz, 1 H), 2.31-2.47 (m, 2 H), 0.94-1.13 (m, 4 H).

Workup

concentrationconcentrated
additionThe residue was diluted with water
additionthe pH of the resulting solution adjusted to 6 by the addition of 1N HCl (3.1 mL) solution
customThe precipitate formed
filtrationwas filtered
customdried under high vacuum

Sources & evidence

ORD record: ord-3fdc8b1aac7d4434beef09f1869ff2f0
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09174992B2

Reaction notes

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