Hexamethylenetetramine → 6-Hydroxy-2-[4-(4-methyl-piperidine-1-carbonyl)-phenyl]-benzothiazole-7-carbaldehyde

HRID 579454Notes

Reaction equation

[OH:1][C:2]1[CH:25]=[CH:24][C:5]2[N:6]=[C:7]([C:9]3[CH:14]=[CH:13][C:12]([C:15]([N:17]4[CH2:22][CH2:21][CH:20]([CH3:23])[CH2:19][CH2:18]4)=[O:16])=[CH:11][CH:10]=3)[S:8][C:4]=2[CH:3]=1.C1N2CN3CN(C2)CN1C3.FC(F)(F)[C:38](O)=[O:39].C([O-])(O)=O.[Na+]>O>[OH:1][C:2]1[CH:25]=[CH:24][C:5]2[N:6]=[C:7]([C:9]3[CH:14]=[CH:13][C:12]([C:15]([N:17]4[CH2:22][CH2:21][CH:20]([CH3:23])[CH2:19][CH2:18]4)=[O:16])=[CH:11][CH:10]=3)[S:8][C:4]=2[C:3]=1[CH:38]=[O:39]

Participants

Conditions

Temperature: 120 °C

Procedure

A mixture of [4-(6-Hydroxy-benzothiazol-2-yl)-phenyl]-(4-methyl-piperidin-1-yl)-methanone (120 mg, 0.34 mmol), hexamethylenetetramine (190 mg, 1.36 mmol) and trifluoroacetic acid (2 mL) was stirred in a closed vessel under argon atmosphere at 120° C. for 1 h. The reaction was cooled to room temperature and 10 mL of water was added. The pH of the mixture was adjusted to 8 by dropwise addition of saturated NaHCO3 solution, and extracted with dichloromethane (3×15 mL). The combined organic layers were dried (MgSO4), filtered and evaporated. The residue was purified by column chromatography on silica (Kieselgel 60), eluting with chloroform-methanol 99:1. The title compound (34 mg, 0.089 mmol, 26%) was obtained as pale yellow crystals.

Workup

temperatureThe reaction was cooled to room temperature
extractionextracted with dichloromethane (3×15 mL)
dry with materialThe combined organic layers were dried (MgSO4)
filtrationfiltered
customevaporated
customThe residue was purified by column chromatography on silica (Kieselgel 60)
washeluting with chloroform-methanol 99:1

Sources & evidence

ORD record: ord-2fc9dd55d94e496fbc17294fc9f9a492
Source dataset: uspto-grants-2015_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09040714B2

Reaction notes

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