Triethylamine → HCID 66673596, compound

HRID 423688Notes

Reaction equation

HRID 423688 reaction equation
[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[CH3:8][S:9]([C:12]1[CH:17]=[CH:16][C:15]([C:18]2[CH:23]=[CH:22][C:21]([O:24][CH2:25][CH:26]3[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]3)=[CH:20][N:19]=2)=[CH:14][CH:13]=1)(=[O:11])=[O:10].Br[C:33]1[S:37][N:36]=[C:35]([CH:38]([CH3:40])[CH3:39])[N:34]=1.C(N(CC)CC)C>ClCCCl>[C:3]([OH:5])([C:2]([F:7])([F:6])[F:1])=[O:4].[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[CH3:39][CH:38]([C:35]1[N:34]=[C:33]([N:29]2[CH2:30][CH2:31][CH:26]([CH2:25][O:24][C:21]3[CH:22]=[CH:23][C:18]([C:15]4[CH:16]=[CH:17][C:12]([S:9]([CH3:8])(=[O:10])=[O:11])=[CH:13][CH:14]=4)=[N:19][CH:20]=3)[CH2:27][CH2:28]2)[S:37][N:36]=1)[CH3:40]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 53408113HCID 53408113, compoundHCID 66673584HCID 66673584, compound

Product 2

HCID 6422Trifluoroacetic acidYield 0.05%HCID 66673596HCID 66673596, compoundYield 37.1%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

A mixture of 2-[4-(methylsulfonyl)phenyl]-5-[(4-piperidinylmethyl)oxy]pyridine trifluoroacetate (107 mg, 0.23 mmol), 5-bromo-3-(1-methylethyl)-1,2,4-thiadiazole (48 mg, 0.23 mmol), triethylamine (0.096 mL, 0.69 mol) and 1,2-dichloroethane (3 mL) was stirred and heated at reflux for 2 h, and the mixture was concentrated. The crude product was purified by reverse-phase preparative HPLC using CH3CN:H2O gradient (30:70 to 70:30) with 0.05% TFA as a modifier to give 25 mg (19%) of the title compound as an off-white solid. 1H NMR (400 MHz, CDCl3): δ 8.49 (d, 1H, J=2.6 Hz), 8.13-8.06 (m, 2H), 8.06-7.99 (m, 2H), 7.76 (d, 1H, J=8.8 Hz), 7.39 (dd, 1H, Ja=8.8 Hz, Jb=2.6 Hz), 4.06-3.94 (m, 4H), 3.27-3.17 (m, 2H), 3.12-2.99 (m, 4H), 2.23-2.08 (m, 1H), 2.05-1.95 (m, 2H), 1.65-1.50 (m, 2H), 1.31 (d, 6H, J=6.9 Hz); LRMS (ESI), m/z 473 (M+H).

Workup

  1. temperatureheated
  2. temperatureat reflux for 2 h
  3. concentrationthe mixture was concentrated
  4. customThe crude product was purified by reverse-phase preparative HPLC

Sources & evidence

ORD record
ord-c4da0cb4647e4dc6a7255744674e787d
Source dataset
uspto-grants-2012_01
Patent number
US08101634B2

Reaction notes

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