Formaldehyde → cis-[5-(1-Methyl-piperidin-4-yl)-thiophen-3-yl]-(octahydro-quinolin-1-yl)-methanone

HRID 1809072Notes

Reaction equation

[N:1]1([C:11]([C:13]2[CH:17]=[C:16]([CH:18]3[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]3)[S:15][CH:14]=2)=[O:12])[C@@H:10]2[C@@H:5]([CH2:6][CH2:7][CH2:8][CH2:9]2)[CH2:4][CH2:3][CH2:2]1.[CH2:24]=O>C(O)=O>[CH3:24][N:21]1[CH2:20][CH2:19][CH:18]([C:16]2[S:15][CH:14]=[C:13]([C:11]([N:1]3[C@@H:10]4[C@@H:5]([CH2:6][CH2:7][CH2:8][CH2:9]4)[CH2:4][CH2:3][CH2:2]3)=[O:12])[CH:17]=2)[CH2:23][CH2:22]1

Participants

Conditions

Temperature: 150 °C

Procedure

cis-(Octahydro-quinolin-1-yl)-(5-piperidin-4-yl-thiophen-3-yl)-methanone (CC-033) (0.070 g, 0.21 mmol) was dissolved in aqueous formaldehyde (37% w/w; 0.1 mL) and formic acid (1 mL). The reaction was heated to 150° C. using microwave irradiation for 5 minutes. The product was purified by flash chromatography on a SCX-2 cartridge, eluting with acetonitrile and then 2 M ammonia in methanol. The residue was further purified by flash chromatography on a NH2-SPE cartridge, eluting with 0%-100% ethyl acetate in cyclohexane. The fractions containing the desired product were concentrated under vacuum to give the title compound (0.035 g). LCMS m/z 347.21 min [M+H]+ RT=6.68 min (Analytical Method 1). 1H NMR (400 MHz, CHCl3-d): δ 7.2 (s, 1H), 6.85 (s, 1H), 4.7 (m, 1H), 3.8 (m, 1H), 3.1 (m, 1H), 2.9 (m, 1H), 2.8-2.7 (m, 1H), 2.30 (s, 3H), 2.1-1.1 (m, 20H).

Workup

custommicrowave irradiation for 5 minutes
customThe product was purified by flash chromatography on a SCX-2 cartridge
washeluting with acetonitrile
customThe residue was further purified by flash chromatography on a NH2-SPE cartridge
washeluting with 0%-100% ethyl acetate in cyclohexane
additionThe fractions containing the desired product
concentrationwere concentrated under vacuum

Sources & evidence

ORD record: ord-6f4cf2fb5a1445108fa6bac3295d7861
Source dataset: uspto-grants-2013_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08362008B2

Reaction notes

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