Hydrochloric Acid → (R)-N-hydroxy-4-(2-methyl-1-(4-(3-phenylisoxazol-5-yl)thiazol-2-ylamino)propyl)benzamide

HRID 1049103Notes

Reaction equation

[CH3:1][CH:2]([CH3:24])[C@H:3]([C:8]1[CH:23]=[CH:22][C:11]([C:12]([NH:14][O:15]C2CCCCO2)=[O:13])=[CH:10][CH:9]=1)[NH:4][C:5]([NH2:7])=[S:6].Br[CH2:26][C:27]([C:29]1[O:33][N:32]=[C:31]([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[CH:30]=1)=O.Cl>O1CCOCC1.C(Cl)Cl>[OH:15][NH:14][C:12](=[O:13])[C:11]1[CH:10]=[CH:9][C:8]([C@H:3]([NH:4][C:5]2[S:6][CH:26]=[C:27]([C:29]3[O:33][N:32]=[C:31]([C:34]4[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=4)[CH:30]=3)[N:7]=2)[CH:2]([CH3:1])[CH3:24])=[CH:23][CH:22]=1

Participants

Conditions

Temperature: 40 °C

Procedure

A mixture of 4-((R)-2-methyl-1-thioureidopropyl)-N-(tetrahydro-2H-pyran-2-yloxy)benzamide (0.0252 g, 0.0717 mmol) and 5-(bromoacetyl)-3-phenylisoxazole (0.0191 g, 0.0717 mmol) in 1,4-dioxane (0.50 mL) was heated at 40° C. for 1 h. The solution was diluted with DCM (0.50 mL) and hydrochloric acid (0.20 mL, 0.80 mmol, 4.00 M of in 1,4-dioxane) was added. The reaction was stirred at rt for 3 h. The mixture was evaporated to dryness, the residue dissolved in DMSO and the solution purified on prep-HPLC to give (R)—N-hydroxy-4-(2-methyl-1-(4-(3-phenylisoxazol-5-yl)thiazol-2-ylamino)propyl)benzamide as a white solid (0.0173 g, 56%). LC-MS: (FA) ES+ 435. 1H NMR (dmso-d6, 400 MHz) δ11.13 (s, 1H), 9.00 (s, 1H), 8.52 (d, J=8.6 Hz, 1H), 7.90 (m, 2H), 7.70 (d, J=8.3 Hz, 2H), 7.51 (dd, J=5.1, 1.9 Hz, 3H), 7.44 (d, J=8.3 Hz, 2H), 7.26 (s, 1H), 7.09 (s, 1H), 4.48 (t, J=8.1 Hz, 1H), 2.10 (m, 1H), 1.00 (d, J=6.6 Hz, 3H), 0.78 (d, J=6.7 Hz, 3H).

Workup

additionwas added
customThe mixture was evaporated to dryness
dissolutionthe residue dissolved in DMSO
customthe solution purified on prep-HPLC

Sources & evidence

ORD record: ord-a1ae3ec129a848078a63e01d9b2b9483
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09382197B2

Reaction notes

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