1-BOC-3-Aminopiperidine → tert-butyl 3-(5-(3-(6-isopropoxypyridin-2-yl)-1-tosyl-1H-indol-5-yl)-1,3,4-thiadiazol-2-ylamino)piperidine-1-carboxylate

HRID 634176Notes

Reaction equation

HRID 634176 reaction equation
[CH:1]([O:4][C:5]1[N:10]=[C:9]([C:11]2[C:19]3[C:14](=[CH:15][CH:16]=[C:17]([C:20]4[S:21][C:22](S(C)(=O)=O)=[N:23][N:24]=4)[CH:18]=3)[N:13]([S:29]([C:32]3[CH:38]=[CH:37][C:35]([CH3:36])=[CH:34][CH:33]=3)(=[O:31])=[O:30])[CH:12]=2)[CH:8]=[CH:7][CH:6]=1)([CH3:3])[CH3:2].[NH2:39][CH:40]1[CH2:45][CH2:44][CH2:43][N:42]([C:46]([O:48][C:49]([CH3:52])([CH3:51])[CH3:50])=[O:47])[CH2:41]1>O1CCOCC1>[CH:1]([O:4][C:5]1[N:10]=[C:9]([C:11]2[C:19]3[C:14](=[CH:15][CH:16]=[C:17]([C:20]4[S:21][C:22]([NH:39][CH:40]5[CH2:45][CH2:44][CH2:43][N:42]([C:46]([O:48][C:49]([CH3:52])([CH3:51])[CH3:50])=[O:47])[CH2:41]5)=[N:23][N:24]=4)[CH:18]=3)[N:13]([S:29]([C:32]3[CH:38]=[CH:37][C:35]([CH3:36])=[CH:34][CH:33]=3)(=[O:31])=[O:30])[CH:12]=2)[CH:8]=[CH:7][CH:6]=1)([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 5458091-BOC-3-AminopiperidineHCID 683282892-(3-(6-isopropoxypyridin-2-yl)-1-tosyl-1H-indol-5-yl)-5-(methylsulfonyl)-1,3,4-thiadiazole

Product 1

HCID 68328847tert-butyl 3-(5-(3-(6-isopropoxypyridin-2-yl)-1-tosyl-1H-indol-5-yl)-1,3,4-thiadiazol-2-ylamino)piperidine-1-carboxylateYield 49%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A yellow solution of 2-(3-(6-isopropoxypyridin-2-yl)-1-tosyl-1H-indol-5-yl)-5-(methylsulfonyl)-1,3,4-thiadiazole (89.3 mg, 0.115 mmol) and (±)-tert-butyl 3-aminopiperidine-1-carboxylate (Combi-Blocks, Inc., San Diego, Calif.; 0.110 mL, 0.573 mmol) in dioxane (1.0 mL) was heated in an open microwave vial at 90° C. for 3.5 d. Chromatographic purification of the resulting dry residue (silica gel, 0-100% EtOAc/Hex) furnished tert-butyl 3-(5-(3-(6-isopropoxypyridin-2-yl)-1-tosyl-1H-indol-5-yl)-1,3,4-thiadiazol-2-ylamino)piperidine-1-carboxylate (38.6 mg, 0.056 mmol, 49%) as a yellow oil: MS (ESI, pos. ion) m/z: 689.2 (M+1). 1H NMR (400 MHz, CDCl3) δ ppm 8.79 (s, 1H), 8.07 (s, 2H), 7.92 (d, J=7.4 Hz, 1H), 7.82 (d, J=8.4 Hz, 4H), 7.59-7.64 (m, 2H), 7.29 (br. s., 1H), 6.61-6.65 (m, 1H), 5.55 (dt, J=12.5, 6.3 Hz, 1H), 3.69 (d, J=13.3 Hz, 2H), 3.48-3.59 (m, 1H), 3.41 (t, J=7.2 Hz, 2H), 2.36-2.39 (m, 2H), 2.35 (s, 3H), 1.55-1.57 (m, 2H), 1.46 (d, J=3.1 Hz, 6H), 1.44 (s, 9H).

Workup

  1. customChromatographic purification of the resulting dry residue (silica gel, 0-100% EtOAc/Hex)

Sources & evidence

ORD record
ord-33c63ffb27ee44a2a9731df50cb40547
Source dataset
uspto-grants-2016_04
Patent number
US09321756B2

Reaction notes

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