2-Bromothiazole → ((3aR,5R,6aR)-5-(((3S*,4S*)-3-Methoxytetrahydro-2H-pyran-4-yl)amino)-2-(thiazol-2-yl)octahydrocyclopenta[c]pyrrol-3a-yl)(3-(trifluoromethyl)-7,8-dihydro-1,6-naphthyridin-6(5H)-yl)methanone

HRID 571362Notes

Reaction equation

HRID 571362 reaction equation
[CH3:1][O:2][C@H:3]1[C@@H:8]([NH:9][C@@H:10]2[CH2:17][C@H:13]3[CH2:14][NH:15][CH2:16][C@@:12]3([C:18]([N:20]3[CH2:29][CH2:28][C:27]4[N:26]=[CH:25][C:24]([C:30]([F:33])([F:32])[F:31])=[CH:23][C:22]=4[CH2:21]3)=[O:19])[CH2:11]2)[CH2:7][CH2:6][O:5][CH2:4]1.Br[C:35]1[S:36][CH:37]=[CH:38][N:39]=1.[F-].[K+]>C(O)C>[CH3:1][O:2][C@H:3]1[C@@H:8]([NH:9][C@@H:10]2[CH2:17][C@H:13]3[CH2:14][N:15]([C:35]4[S:36][CH:37]=[CH:38][N:39]=4)[CH2:16][C@@:12]3([C:18]([N:20]3[CH2:29][CH2:28][C:27]4[N:26]=[CH:25][C:24]([C:30]([F:33])([F:31])[F:32])=[CH:23][C:22]=4[CH2:21]3)=[O:19])[CH2:11]2)[CH2:7][CH2:6][O:5][CH2:4]1

Participants

5

Reactant 3

HCID 764302-BromothiazoleHCID 522689Potassium FluorideHCID 86708896((3aR,5R,6aR)-5-(((3S*,4S*)-3-Methoxytetrahydro-2H-pyran-4-yl)amino)octahydro-cyclopenta[c]pyrrol-3a-yl)(3-(trifluoromethyl)-7,8-dihydro-1,6-naphthyridin-6(5H)-yl)methanone

Product 1

HCID 89928823((3aR,5R,6aR)-5-(((3S*,4S*)-3-Methoxytetrahydro-2H-pyran-4-yl)amino)-2-(thiazol-2-yl)octahydrocyclopenta[c]pyrrol-3a-yl)(3-(trifluoromethyl)-7,8-dihydro-1,6-naphthyridin-6(5H)-yl)methanone

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of Example 1 (HCl salt, 32 mg, 0.0554 mmol), 2-bromothiazole (13.62 mg, 0.0831 mmol), TEA (0.0385 mL, 0.277 mmol) and potassium fluoride (1.61 mg, 0.0277 mmol) in ethanol (1 mL) in a sealed tube was heated at 90° C. for 6 days. After aqueous work up, the residue was purified by CombiFlash (eluent: 5% methanol in DCM) to give the product. 1H-NMR (400 MHz, CDCl3): δ 1.50-1.93 (m, 5H), 2.12-2.47 (m, 2H), 2.65-2.80 (m, 2H), 3.03-4.19 (m, 17H), 4.64-5.01 (m, 2H), 6.55 (d, J=3.5 Hz, 1H), 7.20 (d, J=3.5 Hz, 1H), 7.69 (br. s., 1H), 8.71 (d, J=5.1 Hz, 1H); LC/MS: C26H32F3N5O3S: m/z 552.2 (M+H).

Workup

  1. customAfter aqueous work up, the residue was purified by CombiFlash (eluent: 5% methanol in DCM)
  2. customto give the product

Sources & evidence

ORD record
ord-41e282791a2546cc9178c5b916d6bd85
Source dataset
uspto-grants-2015_05
Patent number
US09024017B2

Reaction notes

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