(3S)-(-)-3-(tert-Butoxycarbonylamino)pyrrolidine → (S)-tert-butyl 1-(5-(3-(6-isopropoxypyridin-2-yl)-1-tosyl-1H-indol-5-yl)-1,3,4-thiadiazol-2-yl)pyrrolidin-3-ylcarbamate

HRID 634179Notes

Reaction equation

HRID 634179 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].[C:39]([O:43][C:44]([NH:46][C@H:47]1[CH2:51][CH2:50][NH:49][CH2:48]1)=[O:45])([CH3:42])([CH3:41])[CH3:40]>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]([N:49]5[CH2:50][CH2:51][C@H:47]([NH:46][C:44](=[O:45])[O:43][C:39]([CH3:41])([CH3:40])[CH3:42])[CH2:48]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:30])=[O:31])[CH:12]=2)[CH:8]=[CH:7][CH:6]=1)([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 1514396(3S)-(-)-3-(tert-Butoxycarbonylamino)pyrrolidineHCID 683282892-(3-(6-isopropoxypyridin-2-yl)-1-tosyl-1H-indol-5-yl)-5-(methylsulfonyl)-1,3,4-thiadiazole

Product 1

HCID 90257007(S)-tert-butyl 1-(5-(3-(6-isopropoxypyridin-2-yl)-1-tosyl-1H-indol-5-yl)-1,3,4-thiadiazol-2-yl)pyrrolidin-3-ylcarbamateYield 90.2%

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 (168.4 mg, 0.296 mmol) and (35)-(−)-3-(tert-butoxycarbonylamino)pyrrolidine (TCI America, Portland, Oreg.; 165 mg, 0.888 mmol) in dioxane (1.0 mL) was heated in an open microwave vial at 90° C. for 2 days. Chromatographic purification of the resulting dry residue (silica gel, 0-100% EtOAc/Hex) furnished (S)-tert-butyl 1-(5-(3-(6-isopropoxypyridin-2-yl)-1-tosyl-1H-indol-5-yl)-1,3,4-thiadiazol-2-yl)pyrrolidin-3-ylcarbamate (180 mg, 0.267 mmol, 90%) as a light-yellow solid: MS (ESI, pos. ion) m/z: 675.1 (M+1). 1H NMR (400 MHz, CDCl3) δ ppm 8.80 (s, 1H), 8.07 (s, 2H), 7.94-7.99 (m, 1H), 7.82 (d, J=8.2 Hz, 2H), 7.62 (t, J=7.8 Hz, 1H), 7.28 (d, J=7.4 Hz, 1H), 7.22-7.25 (m, 2H), 6.63 (d, J=8.2 Hz, 1H), 5.57 (spt, J=6.2 Hz, 1H), 4.72 (br. s., 1H), 4.40 (br. s., 1H), 3.84 (dd, J=10.4, 5.9 Hz, 1H), 3.68-3.75 (m, 1H), 3.60-3.68 (m, 1H), 3.41-3.55 (m, 1H), 3.45 (m, J=10.4, 3.5 Hz, 1H), 2.35 (s, 3H), 1.46 (s, 9H), 1.45 (br. s., 6H).

Workup

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

Sources & evidence

ORD record
ord-71c24ea4438f4c1ebcae94a1fb56ce30
Source dataset
uspto-grants-2016_04
Patent number
US09321756B2

Reaction notes

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