Diisopropylethylamine → 4-[7-(3-Methanesulfonylamino-propoxy)-quinazolin-4-yl]-piperidine-1-carboxylic acid (4-isopropoxy-phenyl)-amide

HRID 657241ノート

反応式

HRID 657241 の反応式
C(O)(C(F)(F)F)=O.C(Cl)(Cl)Cl.C(O[C:17]([N:19]1[CH2:24][CH2:23][CH:22]([C:25]2[C:34]3[C:29](=[CH:30][C:31]([O:35][CH2:36][CH2:37][CH2:38][NH:39][S:40]([CH2:43]C)(=[O:42])=[O:41])=[CH:32][CH:33]=3)[N:28]=[CH:27][N:26]=2)[CH2:21][CH2:20]1)=[O:18])(C)(C)C.[Al].CCN(C(C)C)C(C)C.[N+](C1C=CC(OC(=O)[NH:66][C:67]2[CH:72]=[CH:71][C:70]([O:73][CH:74]([CH3:76])[CH3:75])=[CH:69][CH:68]=2)=CC=1)([O-])=O>C(Cl)Cl.CC(C)=O.C(Cl)(Cl)Cl>[CH:74]([O:73][C:70]1[CH:71]=[CH:72][C:67]([NH:66][C:17]([N:19]2[CH2:20][CH2:21][CH:22]([C:25]3[C:34]4[C:29](=[CH:30][C:31]([O:35][CH2:36][CH2:37][CH2:38][NH:39][S:40]([CH3:43])(=[O:41])=[O:42])=[CH:32][CH:33]=4)[N:28]=[CH:27][N:26]=3)[CH2:23][CH2:24]2)=[O:18])=[CH:68][CH:69]=1)([CH3:76])[CH3:75]

参加物

8

反応物 5

HCID 81531DiisopropylethylamineHCID 5359268AluminumHCID 19978452Chloroform trifluoroacetic acidHCID 58769998(4-Isopropoxy-phenyl)-carbamic acid 4-nitrophenyl esterHCID 693027414-[7-(3-Ethanesulfonylamino-propoxy)-quinazolin-4-yl]-piperidine-1-carboxylic acid tert-butyl ester

生成物 1

HCID 587706584-[7-(3-Methanesulfonylamino-propoxy)-quinazolin-4-yl]-piperidine-1-carboxylic acid (4-isopropoxy-phenyl)-amide

試薬・触媒・溶媒 2

HCID 6212Chloroform溶媒HCID 21584124Propan-2-one--dichloromethane (1/1)溶媒

実験手順

A premixed solution of 1:1 TFA/CHCl3 (80 μL, 539 μmol TFA) was added to 4-[7-(3-ethanesulfonylamino-propoxy)-quinazolin-4-yl]-piperidine-1-carboxylic acid tert-butyl ester (38.7 mg, 83.4 μmol), prepared as described in the previous step, and the tightly capped reaction was stirred under air at 100° C. (aluminum block) for 10 min. After cooling to rt, DIEA (117 μL, 709 μmol) was added dropwise, followed by CHCl3 (0.5 mL), and the resulting homogeneous solution was stirred at rt while (4-isopropoxy-phenyl)-carbamic acid 4-nitro-phenyl ester (32.9 mg, 104 μmol), as prepared in Example 1a, was added in one portion. The resulting homogeneous dark yellow solution was stirred at rt overnight, and then directly loaded onto a flash silica column (5:3 DCM/acetone eluent) to afford impure title compound. This material was taken up in EtOAc (2 mL) and washed with 1.0 M NaHCO3 (3×2 mL), 1.0 M NaH2PO4 (2×2 mL), and again 1.0 M NaHCO3 (2×2 mL). One contaminant was removed (apparently protonated DIEA), but another substantially remained (apparently nitrophenol), so the EtOAc layer was directly loaded onto a flash silica column (5:3 DCM/acetone eluent) to afford the title compound as a white foam (16.0 mg, 35%). 1H-NMR (400 MHz, CDCl3) δ 9.13 (s, 1H), 8.06 (d, 1H), 7.32 (d, 1H), 7.27-7.21 (m, 3H), 6.84 (m, 2H), 6.34 (br s, 1H), 4.69 (br t, 1H), 4.48 (heptet, 1H), 4.26 (m, 4H), 3.67 (tt, 1H), 3.42 (q, 2H), 3.13 (td, 2H), 2.97 (s, 3H), 2.21-2.05 (m, 4H), 2.00-1.91 (m, 2H), 1.32 (d, 6H). LC/MS (ESI): calcd mass 541.2, found 542.1 (MH)+. Anal. Calcd for C27H35N5O5S: C, 59.87; H, 6.51; N, 12.93. Found: C, 60.03; H, 6.51; N, 12.78.

後処理

  1. customprepared
  2. customthe tightly capped reaction
  3. customas prepared in Example 1a
  4. additionwas added in one portion

出典と根拠

ORDレコード
ord-1089123e82b045f089a54fbe51a815ee
出典データセット
uspto-grants-2011_12
特許番号
US08071768B2

反応ノート

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