Hydrochloric Acid → (R)-2-(4-(5-(4-phenyl-5-(trifluoromethyl)thiophen-2-yl)-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-ylamino) ethanol

HRID 1053774Notes

Reaction equation

HRID 1053774 reaction equation
[Si]([O:8][CH2:9][CH2:10][N:11]([C@H:19]1[C:27]2[C:22](=[C:23]([C:28]3[N:32]=[C:31]([C:33]4[S:34][C:35]([C:44]([F:47])([F:46])[F:45])=[C:36]([C:38]5[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=5)[CH:37]=4)[O:30][N:29]=3)[CH:24]=[CH:25][CH:26]=2)[CH2:21][CH2:20]1)C(=O)OC(C)(C)C)(C(C)(C)C)(C)C.Cl.CCOCC>C(Cl)Cl>[C:38]1([C:36]2[CH:37]=[C:33]([C:31]3[O:30][N:29]=[C:28]([C:23]4[CH:24]=[CH:25][CH:26]=[C:27]5[C:22]=4[CH2:21][CH2:20][C@H:19]5[NH:11][CH2:10][CH2:9][OH:8])[N:32]=3)[S:34][C:35]=2[C:44]([F:46])([F:47])[F:45])[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 3283Diethyl EtherHCID 67197415(R)-tert-butyl 2-(tert-butyldimethylsilyloxy)ethyl(4-(5-(4-phenyl-5-(trifluoromethyl)thiophen-2-yl)-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)carbamate

Product 1

HCID 67319515(R)-2-(4-(5-(4-phenyl-5-(trifluoromethyl)thiophen-2-yl)-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-ylamino) ethanolYield 65%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To (R)-tert-butyl 2-(tert-butyldimethylsilyloxy)ethyl(4-(5-(4-phenyl-5-(trifluoromethyl)thiophen-2-yl)-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)carbamate INT-63 (0.108 g, 0.16 mmol) dissolved in DCM (1.5 mL) was added 2N HCl in ether (1.45 mL, 2.9 mmol). The solution was stirred at room temperature for 12 h. The solvent was removed under a stream of nitrogen and the product dried under vacuum to afford 0.052 g (65%) of (R)-2-(4-(5-(4-phenyl-5-(trifluoromethyl)thiophen-2-yl)-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-ylamino) ethanol 67 as the HCl salt. LCMS-ESI (m/z): calcd for C24H20F3N3O2S: 471.5; found 472.1 [M+H]+, tR=7.43 min (Method 2). 1H NMR (400 MHz, CDCl3) δ 9.62 (s, 1H), 8.19 (d, J=7.6, 1H), 8.03 (d, J=7.5, 1H), 7.87 (t, J=1.5, 1H), 7.53-7.40 (m, 6H), 4.86 (d, J=4.8, 1H), 3.88 (s, 2H), 3.74-3.50 (m, 1H), 3.41 (ddd, J=13.3, 9.4, 4.4, 1H), 3.06 (m, 1H), 2.98 (m, 1H), 2.67-2.42 (m, 2H). 13C NMR (100 MHz, DMSO) δ 169.22, 168.07, 145.68, 144.75, 139.39, 135.43, 132.42, 129.42, 129.37, 129.25, 128.69, 128.27, 127.62, 126.41, 123.16, 122.37, 120.47, 61.10, 56.63, 46.54, 31.66, 27.80.

Workup

  1. customThe solvent was removed under a stream of nitrogen
  2. customthe product dried under vacuum

Sources & evidence

ORD record
ord-92d6423ca7234301a2de8b94d0a6e40c
Source dataset
uspto-grants-2016_07
Patent number
US09394264B2

Reaction notes

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