Diisopropylethylamine → 4-[(4-Methyl-1-piperazinyl)methyl]-N-[4-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]benzamide

HRID 468835

反応式

HRID 468835 の反応式
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([CH3:17])=[C:6]([B:8]2[O:16][C:13]([CH3:15])([CH3:14])[C:10]([CH3:12])([CH3:11])[O:9]2)[CH:7]=1.[CH3:18][N:19]1[CH2:24][CH2:23][N:22]([CH2:25][C:26]2[CH:34]=[CH:33][C:29]([C:30](O)=[O:31])=[CH:28][CH:27]=2)[CH2:21][CH2:20]1.F[P-](F)(F)(F)(F)F.N1(O[P+](N2CCCC2)(N2CCCC2)N2CCCC2)C2N=CC=CC=2N=N1.C(N(C(C)C)C(C)C)C>CN(C=O)C.O>[CH3:17][C:5]1[CH:4]=[CH:3][C:2]([NH:1][C:30](=[O:31])[C:29]2[CH:28]=[CH:27][C:26]([CH2:25][N:22]3[CH2:21][CH2:20][N:19]([CH3:18])[CH2:24][CH2:23]3)=[CH:34][CH:33]=2)=[CH:7][C:6]=1[B:8]1[O:16][C:13]([CH3:15])([CH3:14])[C:10]([CH3:11])([CH3:12])[O:9]1

参加物

7

反応物 4

HCID 81531DiisopropylethylamineHCID 47697824-(4-Methyl-1-piperazinylmethyl)benzoic acidHCID 11038641((7-Azabenzotriazol-1-YL)oxy)tris(pyrrolidino)phosphonium hexafluorophosphateHCID 160860894-Methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline

生成物 1

HCID 711151684-[(4-Methyl-1-piperazinyl)methyl]-N-[4-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]benzamide収率 24%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

実験手順

A solution of 5-amino-2-methylphenylboronic acid pinacol ester (1.001 g, 4.294 mmol), 4-((4-methylpiperazin-1-yl)methyl)benzoic acid (1.112 g, 4.746 mmol) and (7-azabenzotriazol-1-yloxy)tripyrrolidinophosphonium hexafluorophosphate (2.446 g, 4.691 mmol) in DMF (20 mL) at ambient temperature was added ethyldiisopropylamine (0.98 mL, 5.6 mmol), the mixture stirred at room temperature for 3 d and poured into water (100 ml). The aqueous phase was washed with diethyl ether, treated with saturated aqueous sodium bicarbonate and extracted twice with ethyl acetate. The combined ethyl acetate extracts were washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified by flash chromatography (silica, ISCO, 10-100% ethyl acetate in heptane, and then 0-20% methanol in DCM modified with 1% ammonia) to afford the title compound as a white solid (456 mg, 24%). 1H NMR (400 MHz, CDCl3) δ 7.97 (dd, J=8.2, 2.0 Hz, 1H), 7.80 (d, J=8.1 Hz, 2H), 7.74 (s, 1H), 7.64 (d, J=2.3 Hz, 1H), 7.44 (d, J=8.1 Hz, 2H), 7.19 (d, J=8.3 Hz, 1H), 3.57 (s, 2H), 2.52 (s, 3H), 2.5 (br s, 8H), 2.31 (s, 3H), 1.35 (s, 12H). LCMS: M+H+=450.4.

後処理

  1. washThe aqueous phase was washed with diethyl ether
  2. additiontreated with saturated aqueous sodium bicarbonate
  3. extractionextracted twice with ethyl acetate
  4. washThe combined ethyl acetate extracts were washed with brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by flash chromatography (silica, ISCO, 10-100% ethyl acetate in heptane

出典と根拠

ORDレコード
ord-6aa7bd2c30a84fef8c210090d5df105f
出典データセット
uspto-grants-2014_01
特許番号
US08623889B2

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