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

HRID 869041ノート

反応式

HRID 869041 の反応式
[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

参加物

4

反応物 2

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

生成物 1

HCID 546708463-[2-[3-Amino-6-[4-(4-piperidylsulfonyl)phenyl]pyrazin-2-yl]ethynyl]phenol収率 6.9%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-8a0f00a8838e414bb954db562d5be8f1
出典データセット
uspto-grants-2015_03
特許番号
US08969356B2

反応ノート

読み込み中…