Diphenyl Ether → HCID 136338252, compound

HRID 1529431Notes

Reaction equation

HRID 1529431 reaction equation
[CH:1]([O:4][C:5]1[N:10]=[C:9]([C:11]2[CH:12]=[C:13]3[C:17](=[CH:18][CH:19]=2)[NH:16][CH:15]=[C:14]3[C:20]2[O:24][C:23](=O)[NH:22][N:21]=2)[CH:8]=[N:7][CH:6]=1)([CH3:3])[CH3:2].CCN(C(C)C)C(C)C.O(C1C=CC=CC=1)C1C=CC=CC=1.[NH:48]1[CH2:53][CH2:52][CH:51]([NH:54][C:55](=[O:61])[O:56][C:57]([CH3:60])([CH3:59])[CH3:58])[CH2:50][CH2:49]1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>CN(C=O)C.O>[CH:1]([O:4][C:5]1[N:10]=[C:9]([C:11]2[CH:12]=[C:13]3[C:17](=[CH:18][CH:19]=2)[NH:16][CH:15]=[C:14]3[C:20]2[O:24][C:23]([N:48]3[CH2:49][CH2:50][CH:51]([NH:54][C:55](=[O:61])[O:56][C:57]([CH3:59])([CH3:58])[CH3:60])[CH2:52][CH2:53]3)=[N:22][N:21]=2)[CH:8]=[N:7][CH:6]=1)([CH3:3])[CH3:2]

Participants

8

Reactant 5

HCID 7583Diphenyl EtherHCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 7238334-(N-Boc-amino)piperidineHCID 136338251HCID 136338251, compound

Product 1

HCID 136338252HCID 136338252, compoundYield 21%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 5-(5-(6-isopropoxypyrazin-2-yl)-1H-indol-3-yl)-1,3,4-oxadiazol-2(3H)-one (0.25 g, 0.74 mmol) in anhydrous DMF (2.5 mL) was added DIPEA (0.25 mL, 1.48 mmol), Ph2O (125 mg, 0.74 mmol) and tert-butyl piperidin-4-ylcarbamate (0.295 g, 1.4 mmol) sequentially. The reaction was stirred for 5 min, BOP (360 mg, 0.8 mmol) was added and the reaction was further stirred for 12 h at RT. The mixture was diluted with water (25 mL) and the resulting suspension was filtered. The solid was triturated with 50% EtOAc in petroleum ether to give tert-butyl (1-(5-(5-(6-isopropoxypyrazin-2-yl)-1H-indol-3-yl)-1,3,4-oxadiazol-2-yl)piperidin-4-yl)carbamate (80 mg, 21%) as a solid. MS (ESI, pos. ion) m/z: 520.3 (M+1); 1H NMR (400 MHz, DMSO-d6): δ ppm: 12.01 (s, 1H), 8.74 (s, 2H), 8.13 (s, 1H), 8.07 (s, 1H), 7.98 (d, J=8.4 Hz, 1H), 7.63 (d, J=8.4 Hz, 1H), 7.00 (d, J=7.2 Hz, 1H), 5.40-5.46 (m, 1H), 3.73-3.87 (m, 2H), 3.50 (s, 1H), 3.16 (t, J=10.6 Hz, 1H), 2.98 (t, J=9.2 Hz 1H), 1.84 (s, 2H), 1.33 (s, 17H).

Workup

  1. stirringthe reaction was further stirred for 12 h at RT
  2. filtrationthe resulting suspension was filtered
  3. customThe solid was triturated with 50% EtOAc in petroleum ether

Sources & evidence

ORD record
ord-2af595b49d664212add157024280be99
Source dataset
uspto-grants-2015_07
Patent number
US09090593B2

Reaction notes

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