Hydrochloric Acid → 4-(5-(1-Cyclobutylcyclopropyl)thiazolo[5,4-b]pyridin-2-yl)-3-fluorobenzaldehyde

HRID 1177593Notes

Reaction equation

[O:1]1CCCO[CH:2]1[C:7]1[CH:12]=[CH:11][C:10]([C:13]2[S:14][C:15]3[C:20]([N:21]=2)=[CH:19][CH:18]=[C:17]([C:22]2([CH:25]4[CH2:28][CH2:27][CH2:26]4)[CH2:24][CH2:23]2)[N:16]=3)=[C:9]([F:29])[CH:8]=1.Cl.[OH-].[Na+]>C1COCC1>[CH:25]1([C:22]2([C:17]3[N:16]=[C:15]4[S:14][C:13]([C:10]5[CH:11]=[CH:12][C:7]([CH:2]=[O:1])=[CH:8][C:9]=5[F:29])=[N:21][C:20]4=[CH:19][CH:18]=3)[CH2:24][CH2:23]2)[CH2:26][CH2:27][CH2:28]1

Participants

Conditions

Temperature: 65 °C

Procedure

A mixture of 2-(4-(1,3-dioxan-2-yl)-2-fluorophenyl)-5-(1-cyclobutyl-cyclopropyl)-thiazolo[5,4-b]pyridine (85.7 mg, 0.209 mmol) and hydrochloric acid (5.0N, aq.) (2.00 mL, 10.02 mmol) in THF (4.0 mL) was stirred at 65° C. for 3 h. The reaction mixture was then cooled on an ice bath, and NaOH (5.0N, aq., 2.0 mL) was added. THF was removed in vacuo, and the resulting mixture was partitioned between EtOAc and water. The organic layer was separated, sequentially washed with water and brine, dried over sodium sulfate, filtered, and concentrated in vacuo. Chromatographic purification of the residue (silica gel, 0-30% EtOAc/hexanes) furnished 4-(5-(1-cyclobutylcyclopropyl)thiazolo[5,4-b]pyridin-2-yl)-3-fluorobenzaldehyde as a light yellow solid. MS (ESI) m/z: Calculated: 352.1; Observed: 353.1 (M++1).

Workup

temperatureThe reaction mixture was then cooled on an ice bath
customTHF was removed in vacuo
customthe resulting mixture was partitioned between EtOAc and water
customThe organic layer was separated
washsequentially washed with water and brine
dry with materialdried over sodium sulfate
filtrationfiltered
concentrationconcentrated in vacuo
customChromatographic purification of the residue (silica gel, 0-30% EtOAc/hexanes)

Sources & evidence

ORD record: ord-7ab589be883e44bfbf0a535a689a35e0
Source dataset: uspto-grants-2010_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07842685B2

Reaction notes

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