HCID 178462262, compound → HCID 178462258, compound

HRID 914043Notes

Reaction equation

HRID 914043 reaction equation
[Cl: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]([Cl:11])[CH:9]=2)[NH:4][N:3]=1>FC(F)(F)C(O)=O>[Cl: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]([Cl:11])[CH:9]=2)[NH:4][N:3]=1

Participants

3

Reactant 1

HCID 178462262HCID 178462262, compound

Product 1

HCID 178462258HCID 178462258, compound

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

(R)-tert-Butyl 4-((1-(3,5-dichloro-1H-indazol-7-yl)ethoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate (4.6 g, 8.80 mmol) was dissolved in trifluoroacetic acid (20% in dichloromethane, 40 mL) and stirred at room temperature for 30 min. The reaction was concentrated and loaded onto a 20 g phenomenex strata giga tube strong cation exchange cartridge. After flushing the cartridge with several volumes of methanol (which were discarded), the product was eluted with 2M ammonia in methanol to give 3.75 g (100%) as a foam solid. 1H-NMR (CDCl3, 500 MHz) δ 9.88 (bs, 1H), 7.51 (d, J=1.1 Hz, 1H), 7.26 (dd, J=8.9, 5.5 Hz, 2H), 7.06 (dd, J=8.5, 8.5 Hz, 2H), 7.01 (d, J=1.1 Hz, 1H), 4.49 (q, J=6.4 Hz, 1H), 3.41 (d, J=8.9 Hz, 1H), 3.27 (d, J=8.9 Hz, 1H), 2.91 (m, 2H), 2.73 (m, 2H), 2.20 (m, 1H), 2.05 (m, 1H), 1.87 (m, 2H), 1.42 (d, J=6.6 Hz, 3H); 13C NMR (126 MHz, CDCl3) δ ppm 161.4 (d, J=246 Hz), 139.0, 136.9, 134.1, 128.5 (d, J=7.8 Hz), 128.3, 126.8, 125.2, 121.9, 117.7, 115.5 (d, J=21 Hz), 79.0, 77.9, 42.4, 42.3, 41.2, 33.5, 33.2, 22.0. Mass spec.: 328.12 (MH)+.

Workup

  1. concentrationThe reaction was concentrated
  2. customAfter flushing the cartridge with several volumes of methanol (which were discarded)
  3. washthe product was eluted with 2M ammonia in methanol
  4. customto give 3.75 g (100%) as a foam solid

Sources & evidence

ORD record
ord-a901afa34ca8423f8f81cec4d277a221
Source dataset
uspto-grants-2011_09
Patent number
US08026257B2

Reaction notes

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