HCID 178462261, compound → HCID 178462257, compound

HRID 914045Notes

Reaction equation

HRID 914045 reaction equation
[Br:1][C:2]1[C:10]2[C:5](=[C:6]([C@H:12]([O:14][CH2:15][C:16]3([C:29]4[CH:34]=[CH:33][C:32]([F:35])=[CH:31][CH:30]=4)[CH2:21][CH2:20][N:19](C(OC(C)(C)C)=O)[CH2:18][CH2:17]3)[CH3:13])[CH:7]=[C:8]([Br:11])[CH:9]=2)[NH:4][N:3]=1>FC(F)(F)C(O)=O.CO>[Br:1][C:2]1[C:10]2[C:5](=[C:6]([C@H:12]([O:14][CH2:15][C:16]3([C:29]4[CH:30]=[CH:31][C:32]([F:35])=[CH:33][CH:34]=4)[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]3)[CH3:13])[CH:7]=[C:8]([Br:11])[CH:9]=2)[NH:4][N:3]=1

Participants

4

Reactant 1

HCID 178462261HCID 178462261, compound

Product 1

HCID 178462257HCID 178462257, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

(R)-tert-Butyl 4-((1-(3,5-dibromo-1H-indazol-7-yl)ethoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate (99 mg, 0.16 mmol) was dissolved in trifluoroacetic acid (20% in dichloromethane, 6 mL) and stirred for 30 min. The reaction was concentated and the resulting residue loaded onto a strong cation exchange cartridge in methanol. The cartridge was washed with several volumes of methanol which were discarded. The product was eluted with 2M ammonia in methanol and concentrated to give 82 mg (94%) as a foam solid. 1H-NMR (CDCl3, 500 MHz) δ 7.62 (d, J=1.5 Hz, 1H), 7.25 (dd, J=9.5, 5.8 Hz, 2H), 7.12 (d, J=1.5 Hz, 1H), 7.03 (dd, J=8.6, 8.6 Hz, 2H), 4.46 (q, J=6.7 Hz, 1H), 3.44 (s, 2H), 3.36 (d, J=8.9 Hz, 1H), 3.24 (d, J=9.2 Hz, 1H), 2.87 (m, 2H), 2.68 (m, 2H), 2.14 (m, 1H), 2.03 (m, 1H), 1.84 (m, 2H), 1.41 (d, J=6.4 Hz, 3H); 13C NMR (126 MHz, CDCl3) δ ppm 161.5 (d, J=246 Hz), 139.3, 137.3, 128.7, 128.61, 128.57, 127.7, 125.3, 121.7, 121.6, 115.6, 115.5, 114.3, 79.0, 77.8, 50.5, 42.5, 42.4, 41.4, 33.7, 33.4, 22.1.

Workup

  1. washThe cartridge was washed with several volumes of methanol which
  2. washThe product was eluted with 2M ammonia in methanol
  3. concentrationconcentrated
  4. customto give 82 mg (94%) as a foam solid

Sources & evidence

ORD record
ord-57b46402d5b6481b8f7940acfb9091ce
Source dataset
uspto-grants-2011_09
Patent number
US08026257B2

Reaction notes

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