Trifluoroacetic acid → 3-[2-[3-Amino-6-[4-(4-piperidylsulfonyl)phenyl]pyrazin-2-yl]ethynyl]phenol

HRID 869041Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 869041
[NH2:1][C:2]1[N:3]=[CH:4][C:5]([C:17]2[CH:22]=[CH:21][C:20]([S:23]([CH:26]3[CH2:31][CH2:30][N:29](C(OC(C)(C)C)=O)[CH2:28][CH2:27]3)(=[O:25])=[O:24])=[CH:19][CH:18]=2)=[N:6][C:7]=1[C:8]#[C:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([OH:16])[CH:11]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:1][C:2]1[C:7]([C:8]#[C:9][C:10]2[CH:11]=[C:12]([OH:16])[CH:13]=[CH:14][CH:15]=2)=[N:6][C:5]([C:17]2[CH:22]=[CH:21][C:20]([S:23]([CH:26]3[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]3)(=[O:24])=[O:25])=[CH:19][CH:18]=2)=[CH:4][N:3]=1

Komponenten

4

Edukt 2

HCID 6422Trifluoroacetic acidHCID 67478804Tert-butyl 4-[4-[5-amino-6-[2-(3-hydroxyphenyl)ethynyl]pyrazin-2-yl]phenyl]sulfonylpiperidine-1-carboxylate

Produkt 1

HCID 546708463-[2-[3-Amino-6-[4-(4-piperidylsulfonyl)phenyl]pyrazin-2-yl]ethynyl]phenolAusbeute 6,9 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

Crude tert-butyl 4-[4-[5-amino-6-[2-(3-hydroxyphenyl)ethynyl]pyrazin-2-yl]phenyl]sulfonylpiperidine-1-carboxylate (184.3 mg, 0.3447 mmol—assumed quantitative yield from Step 3) was dissolved in DCM (5 mL) and TFA (1 mL, 12.98 mmol) was added. The reaction mixture was stirred at ambient temperature for 4 hours. The solvent was removed in vacuo and the residue azeotroped with DCM (×2) and ether (×2). The material was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 μM, 100 Å column, gradient 10%-95% B (solvent A: 0.05% TFA in water; solvent B: CH3CN) over 16 minutes at 25 mL/min]. The fractions were collected and freeze-dried to give the mono-TFA salt of the title compound as a yellow solid (10.3 mg, 5% Yield). 1H NMR (400.0 MHz, DMSO) δ 1.65-1.74 (m, 2H), 2.06 (d, 2H), 2.85-2.90 (m, 2H), 3.36 (d, 2H), 3.59-3.65 (m, 1H), 6.89 (dd, 1H), 7.14-7.21 (m, 2H), 7.27 (t, 1H), 7.90 (d, 2H), 8.23 (br s, 1H), 8.28 (d, 2H), 8.54 (br s, 1H), 8.77 (s, 1H) and 9.78 (s, 1H) ppm; MS (ES+) 435.1.

Aufarbeitung

  1. customThe solvent was removed in vacuo
  2. customthe residue azeotroped with DCM (×2) and ether (×2)
  3. customThe material was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 μM, 100 Å column, gradient 10%-95% B (solvent A: 0.05% TFA in water; solvent B: CH3CN) over 16 minutes at 25 mL/min]
  4. customThe fractions were collected
  5. customfreeze-dried

Quellen und Nachweise

ORD-Eintrag
ord-8a0f00a8838e414bb954db562d5be8f1
Quelldatensatz
uspto-grants-2015_03
Patentnummer
US08969356B2

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