2,4,6-Trimethylpyridine → Plasma kallikrein-IN-3

HRID 928386

反応式

HRID 928386 の反応式
[NH2:1][CH2:2][C:3]1[C:4]([CH3:18])=[CH:5][C:6]([NH:10]C(=O)OC(C)(C)C)=[N:7][C:8]=1[CH3:9].C1C=NC2N(O)N=NC=2C=1.N1C(C)=CC(C)=CC=1C.[CH3:38][O:39][C:40]1[CH:54]=[CH:53][C:43]([CH2:44][N:45]2[CH:49]=[C:48]([C:50](O)=[O:51])[CH:47]=[N:46]2)=[CH:42][CH:41]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl>[NH2:10][C:6]1[N:7]=[C:8]([CH3:9])[C:3]([CH2:2][NH:1][C:50]([C:48]2[CH:47]=[N:46][N:45]([CH2:44][C:43]3[CH:53]=[CH:54][C:40]([O:39][CH3:38])=[CH:41][CH:42]=3)[CH:49]=2)=[O:51])=[C:4]([CH3:18])[CH:5]=1

参加物

7

反応物 5

HCID 79532,4,6-TrimethylpyridineHCID 181649HOAtHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 22475372N-[5-(aminomethyl)-4,6-dimethyl(2-pyridyl)] (tert-butoxy)carboxamideHCID 435653621-[(4-methoxyphenyl)methyl]-1H-pyrazole-4-carboxylic acid

生成物 1

HCID 56836258Plasma kallikrein-IN-3

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

To a mixture of tert-butyl 5-(aminomethyl)-4,6-dimethylpyridin-2-ylcarbamate (80.0 mg, 0.318 mmol) in DCM (3 ml) were added HOAt (87.0 mg, 0.637 mmol), collidine (0.127 ml, 0.955 mmol), 1-(4-methoxybenzyl)-1H-pyrazole-4-carboxylic acid (73.9 mg, 0.318 mmol) and HATU (81.0 mg, 0.212 mmol). After stirring for 2 h at rt, all volatiles were removed in vacuo. The crude intermediate was purified by column chromatography (CombiFlash Companion, 12 g SiO2, TBME to TBME+10% MeOH), dissolved in DCM (3 ml) and TFA (1 ml), kept for 14 h at rt, and concentrated. Purification by column chromatography (CombiFlash Rf, 13 g RediSep Rf C18, MeCN:water 5:95+0.1% TFA to MeCN) afforded the title compound as. 1H-NMR (DMSO-d6, 400 MHz): 2.37 (s, 3H), 3.73 (s, 3H), 4.27 (d, 2H), 5.24 (s, 1H), 6.64 (s, 1H), 6.91 (d, 2H), 7.23 (d, 2H), 7.70 (br, s, 2H), 7.84 (s, 1H), 8.14-8.19 (m, 2H), 13.59 (s, 1H). LCMS RtK=0.71 min, [M+H]+=366.4.

後処理

  1. customall volatiles were removed in vacuo
  2. customThe crude intermediate was purified by column chromatography (CombiFlash Companion, 12 g SiO2, TBME to TBME+10% MeOH)
  3. dissolutiondissolved in DCM (3 ml)
  4. waitTFA (1 ml), kept for 14 h at rt
  5. concentrationconcentrated
  6. customPurification by column chromatography (CombiFlash Rf, 13 g RediSep Rf C18, MeCN:water 5:95+0.1% TFA to MeCN)

出典と根拠

ORDレコード
ord-e5299a8db0764af3a2a8efb53e6a0711
出典データセット
uspto-grants-2016_03
特許番号
US09290485B2

関連ノート

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