Water → HCID 52920357, compound

HRID 250105Notes

Reaction equation

[Cl:1][C:2]1[N:7]=[C:6]2[S:8][C:9]([N:11]=[C:12](SC)SC)=[N:10][C:5]2=[CH:4][CH:3]=1.Cl.Cl.[NH2:19][CH2:20][C@@:21]1([OH:29])[CH:26]2[CH2:27][CH2:28][N:23]([CH2:24][CH2:25]2)[CH2:22]1.C(=O)([O-])[O-].[Cs+].[Cs+].O>CN(C=O)C>[Cl:1][C:2]1[N:7]=[C:6]2[S:8][C:9]([NH:11][C:12]3[O:29][C@:21]4([CH2:20][N:19]=3)[CH:26]3[CH2:27][CH2:28][N:23]([CH2:24][CH2:25]3)[CH2:22]4)=[N:10][C:5]2=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of dimethyl 5-chlorothiazolo[5,4-b]pyridin-2-ylcarbonimidodithioate (100 mg, 0.35 mmol), (S)-3-(aminomethyl)quinuclidin-3-ol dihydrochloride (79 mg, 0.35 mmol) and cesium carbonate (225 mg, 0.69 mmol) in DMF (1.7 mL) was heated to 100° C. for 2 hours. The reaction mixture was cooled to ambient temperature, poured into water and the solids collected by filtration. The crude solids were purified by silica gel chromatography (2-40% 9:1 methanol:ammonium hydroxide-chloroform) to afford (R)—N-(5-chlorothiazolo[5,4-b]pyridin-2-yl)-4H-1′-azaspiro[oxazole-5,3′ bicyclo[2.2.2]octan]-2-amine (62 mg, 51% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 9.13 (br. s., 1 H) 7.93 (d, J=8.53 Hz, 1 H) 7.45 (d, J=8.28 Hz, 1 H) 3.92 (d, J=10.29 Hz, 1 H) 3.67 (d, J=10.29 Hz, 1 H) 3.00-3.14 (m, 2 H) 2.77-2.93 (m, 2 H) 2.69 (t, J=7.65 Hz, 2 H) 2.12 (br. s., 1 H) 1.95 (br. s., 1 H) 1.43-1.72 (m, 3 H). MS (LC/MS) R.T.=1.10; [M+H]+=350.10.

Workup

temperatureThe reaction mixture was cooled to ambient temperature
filtrationthe solids collected by filtration
customThe crude solids were purified by silica gel chromatography (2-40% 9:1 methanol:ammonium hydroxide-chloroform)

Sources & evidence

ORD record: ord-a377e17ac3874c2eab5029d54c8d5c57
Source dataset: uspto-grants-2011_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07863291B2

Reaction notes

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