Benzyl 4-((5-bromo-2-pivalamidopyridin-4-ylamino)methyl)piperidine-1-carboxylate → 5-bromo-N4-(piperidin-4-ylmethyl)pyridine-2,4-diamine

HRID 556860ノート

反応式

HRID 556860 の反応式
[Br:1][C:2]1[C:3]([NH:15][CH2:16][CH:17]2[CH2:22][CH2:21][N:20](C(OCC3C=CC=CC=3)=O)[CH2:19][CH2:18]2)=[CH:4][C:5]([NH:8]C(=O)C(C)(C)C)=[N:6][CH:7]=1>Cl>[Br:1][C:2]1[C:3]([NH:15][CH2:16][CH:17]2[CH2:18][CH2:19][NH:20][CH2:21][CH2:22]2)=[CH:4][C:5]([NH2:8])=[N:6][CH:7]=1

参加物

3

反応物 1

HCID 59613492Benzyl 4-((5-bromo-2-pivalamidopyridin-4-ylamino)methyl)piperidine-1-carboxylate

生成物 1

HCID 667464985-bromo-N4-(piperidin-4-ylmethyl)pyridine-2,4-diamine収率 92.2%

試薬・触媒・溶媒 1

HCID 313Hydrochloric Acid溶媒

反応条件

温度
105 °C

実験手順

A mixture of benzyl 4-((5-bromo-2-pivalamidopyridin-4-ylamino)methyl)piperidine-1-carboxylate (0.695 g, 1.24 mmol) and 6M HCl (10 mL) was heated at 105° C. for 45 mins by microwave irradiation. After cooling the volatiles were removed in vacuo. The residue was redissolved in MeOH and adsorbed onto (solute SCX-II acidic resin. The resin was washed with methanol, then 2M ammonia in methanol. The basic fractions were concentrated to give crude 5-bromo-N4-(piperidin-4-ylmethyl)pyridine-2,4-diamine (0.326 g, 92%), LCMS (4) Rt=0.51 min; m/z (ESI+) 285/287 (MH+). A solution of di-tert-butyl dicarbonate (0.249 g, 1 eq.) in dichloromethane (1 mL) was added dropwise to an ice-cooled solution of 5-bromo-N4-(piperidin-4-ylmethyl)pyridine-2,4-diamine (0.326 g, 1.14 mmol) and triethylamine (0.48 mL, 3 eq.) in dichloromethane (7.79 mL). The solution was stirred at 0° C. for 30 mis and then warmed to room temperature and stirred for a further 30 min. The mixture was concentrated. The crude product was purified by preparative TLC, eluting with 7% MeOH, 1% NH3, 92% dichloromethane, to give tert-butyl 4-((2-amino-5-bromopyridin-4-ylamino)methyl)piperidine-1-carboxylate (234 mg, 53%) as a white powder.

後処理

  1. temperatureAfter cooling the volatiles
  2. customwere removed in vacuo
  3. dissolutionThe residue was redissolved in MeOH
  4. washThe resin was washed with methanol
  5. concentrationThe basic fractions were concentrated

出典と根拠

ORDレコード
ord-e7fe488871934e8a97122f8b587b88e4
出典データセット
uspto-grants-2011_11
特許番号
US08058045B2

反応ノート

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