Trifluoroacetic acid → HCID 58020248, compound

HRID 1632110Notes

Reaction equation

HRID 1632110 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[C:13]([O:14][CH3:15])=[CH:12][CH:11]=[C:10]([CH2:16][C:17]3[CH:22]=[CH:21][N:20]=[C:19]([N:23]4[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]4)[CH:18]=3)[C:9]=2[F:29])[CH:5]=[CH:6][CH:7]=1.FC(F)(F)[C:32]([OH:34])=[O:33]>ClCCl>[C:4]([O:34][C:32]([N:26]1[CH2:27][CH2:28][N:23]([C:19]2[CH:18]=[C:17]([CH2:16][C:10]3[C:9]([F:29])=[C:8]([C:4]4[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[CH:3]=4)[C:13]([O:14][CH3:15])=[CH:12][CH:11]=3)[CH:22]=[CH:21][N:20]=2)[CH2:24][CH2:25]1)=[O:33])([CH3:8])([CH3:5])[CH3:3]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 58019969HCID 58019969, compound

Product 1

HCID 58020248HCID 58020248, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Synthesis of 1-[4-(3′-Chloro-2-fluoro-6-methoxy-biphenyl-3-ylmethyl)-pyridin-2-yl]-piperazine (P-515) In a 40 mL vial equipped with a stir bar was placed I-274 (360 mg, 0.703 mmol) and dichlormethane (2.3 mL). The solution was cooled in an ice-water bath for 10 minutes and then trifluoroacetic acid (522 μL, 7.03 mmol) was added. The solution was stirred at room temperature for 3 hours and then concentrated by a stream of nitrogen. To the oil was added water (50 mL), a saturated sodium bicarbonate solution (till pH 8) followed by extractions with dichloromethane (2×75 mL). The organic portions were combined, washed with brine (50 mL), dried (MgSO4) and concentrated. The residue was purified by column utilizing 10%, 15% and then 20% methanol/dichloromethane as the eluent to produce 120 mg of P-515 as an off-white solid in 41% yield. 1H NMR (400 MHz, DMSO-d6) δ 2.80 (t, J=5 Hz, 4H), 3.39 (t, J=5 Hz, 4H), 3.73 (s, 3H), 3.84 (s, 2H), 6.46 (d, J=5 Hz, 1H), 6.69 (s, 1H), 6.94 (d, J=8 Hz, 1H), 7.28 (bd, J=7 Hz, 1H), 7.32 (t, J=9 Hz, 1H), 7.36 (s, 1H), 7.41-7.47 (m, 2H), 7.98 (d, J=5 Hz, 1H) ppm. MS (APCI+): 412.1 (M+1); LC-MS: >99%.

Workup

  1. customvial equipped with a stir bar
  2. temperatureThe solution was cooled in an ice-water bath for 10 minutes
  3. concentrationconcentrated by a stream of nitrogen
  4. additionTo the oil was added water (50 mL)
  5. extractiona saturated sodium bicarbonate solution (till pH 8) followed by extractions with dichloromethane (2×75 mL)
  6. washwashed with brine (50 mL)
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated
  9. customThe residue was purified by column
  10. custom20% methanol/dichloromethane as the eluent to produce 120 mg of P-515 as an off-white solid in 41% yield

Sources & evidence

ORD record
ord-0b149d03999d4076b34941e436cde5de
Source dataset
uspto-grants-2014_07
Patent number
US08791267B2

Reaction notes

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