Diethyl Ether → N-[3-(7-hydroxy-6-{6-[methyl-(2,2,6,6-tetramethyl-piperidin-4-yl)-amino]-pyridazin-3-yl}-naphthalen-2-yloxy)-propyl]-acetamide

HRID 1027202

反応式

HRID 1027202 の反応式
[C:1](ON1C(=O)CCC1=O)(=[O:3])[CH3:2].[NH2:12][CH2:13][CH2:14][CH2:15][O:16][C:17]1[CH:26]=[C:25]2[C:20]([CH:21]=[C:22]([C:28]3[N:29]=[N:30][C:31]([N:34]([CH3:45])[CH:35]4[CH2:40][C:39]([CH3:42])([CH3:41])[NH:38][C:37]([CH3:44])([CH3:43])[CH2:36]4)=[CH:32][CH:33]=3)[C:23]([OH:27])=[CH:24]2)=[CH:19][CH:18]=1.CCOCC>CS(C)=O>[OH:27][C:23]1[CH:24]=[C:25]2[C:20]([CH:19]=[CH:18][C:17]([O:16][CH2:15][CH2:14][CH2:13][NH:12][C:1](=[O:3])[CH3:2])=[CH:26]2)=[CH:21][C:22]=1[C:28]1[N:29]=[N:30][C:31]([N:34]([CH3:45])[CH:35]2[CH2:40][C:39]([CH3:41])([CH3:42])[NH:38][C:37]([CH3:44])([CH3:43])[CH2:36]2)=[CH:32][CH:33]=1

参加物

5

反応物 3

HCID 3283Diethyl EtherHCID 84460Acetic acid N-hydroxysuccinimide esterHCID 1366337287-(3-Amino-propoxy)-3-{6-[methyl-(2,2,6,6-tetramethyl-piperidin-4-yl)-amino]-pyridazin-3-yl}-naphthalen-2-ol

生成物 1

HCID 136598208N-[3-(7-hydroxy-6-{6-[methyl-(2,2,6,6-tetramethyl-piperidin-4-yl)-amino]-pyridazin-3-yl}-naphthalen-2-yloxy)-propyl]-acetamide収率 55%

試薬・触媒・溶媒 1

HCID 679Dimethyl Sulfoxide溶媒

実験手順

N-Acetoxysuccinimide (98 mg, 0.624 mmol) was added to a solution of Example 20-5 (50 mg, 0.108 mmol) and TEA (0.747 ml, 5.39 mmol) in DMSO (2 ml) at RT. The reaction mixture was stirred at RT for 30 min then concentrated in vacuo to remove excess Et3N. The resulting residue was purified by preparative HPLC (eluting with 5-80% MeCN/H2O with 0.1% TFA modifier). The appropriate fractions containing product were combined then adsorbed onto a MeOH conditioned SCX column (5 g, BSA Varian brand). The column was washed several times with MeOH then eluted with 3 N NH3 in MeOH. Evaporation of the solvent afforded a yellow oil. Et2O was added to the oil then concentrated to dryness affording the title compound as a yellowish orange solid (30 mg, 55% yield). LCMS Rt=0.52 min (LCMS method Q); MS (M+1)=506.2. 1H NMR (400 MHz, DMSO-d6) δ ppm 13.27 (br. s, 1H), 8.35 (s, 1H), 8.28 (d, J=10.10 Hz, 1H), 7.77 (d, J=9.09 Hz, 2H), 7.35 (d, J=9.60 Hz, 1H), 7.17 (s, 1H), 7.09 (d, J=2.02 Hz, 1H), 6.95 (dd, J=9.09, 2.53 Hz, 1H), 4.92-5.04 (m, 1H), 4.11 (t, J=6.32 Hz, 2H), 3.20-3.28 (m, 2H), 2.98 (s, 3H), 1.87-1.96 (m, 2H), 1.82 (s, 3H), 1.55-1.63 (m, 2H), 1.44-1.55 (m, 2H), 1.30 (s, 6H), 1.14 (s, 6H).

後処理

  1. concentrationthen concentrated in vacuo
  2. customto remove excess Et3N
  3. customThe resulting residue was purified by preparative HPLC (eluting with 5-80% MeCN/H2O with 0.1% TFA modifier)
  4. additionThe appropriate fractions containing product
  5. washThe column was washed several times with MeOH
  6. washthen eluted with 3 N NH3 in MeOH
  7. customEvaporation of the solvent
  8. customafforded a yellow oil
  9. concentrationthen concentrated to dryness

出典と根拠

ORDレコード
ord-80eb54301c5a4eb08113125195fe1462
出典データセット
uspto-grants-2014_05
特許番号
US08729263B2

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