Triethylamine → HCID 66710459、化合物

HRID 1777501ノート

反応式

HRID 1777501 の反応式
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([OH:10])=O)=[N:6][CH:7]=1.Cl.Cl.[C:13]([C:15]1[CH:28]=[CH:27][C:18]([CH2:19][N:20]2[CH2:25][CH2:24][CH:23]([NH2:26])[CH2:22][CH2:21]2)=[CH:17][CH:16]=1)#[N:14].C(N(CC)CC)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C)C=O>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([NH:26][CH:23]2[CH2:24][CH2:25][N:20]([CH2:19][C:18]3[CH:27]=[CH:28][C:15]([C:13]#[N:14])=[CH:16][CH:17]=3)[CH2:21][CH2:22]2)=[O:10])=[N:6][CH:7]=1

参加物

6

反応物 4

HCID 8471TriethylamineHCID 6085445-Bromopyridine-2-carboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 44120478HCID 44120478、化合物

生成物 1

HCID 66710459HCID 66710459、化合物

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

To a solution of 5-bromopicolinic acid (0.50 g, 2.48 mmol, 1.0 eq) and 1-(4-cyanobenzyl)-4-aminopiperidine dihydrochloride (0.71 g, 2.48 mmol, 1.0 eq) in dimethylformamide (10 mL) was added triethylamine (1.21 mL, 8.66 mmol, 3.5 eq) and HATU (1.13 g, 2.97 mmol, 1.2 eq). The reaction mixture was stirred at room temperature 14 hours before partitioning between EtOAc (120 mL) and water (100 mL). The organics were washed with brine (100 mL), water (100 mL) and brine (100 mL), dried (Na2SO4) and concentrated under reduced pressure. MPLC (0%, 5%, 10% MeOH—CH2Cl2, 0→5→25→35 min) yielded 5-bromo-N-(1-(4-cyanobenzyl)piperidin-4-yl)picolinamide as a waxy brown solid: 1H nmr (CDCl3) 8.60 (1H, d, J 2.0 Hz, pyH-6), 8.07 (1H, d, J 8.5 Hz, pyH-3), 7.97 (1H, dd, J 8.5, 2.0 Hz, pyH-4), 7.84 (1H, d, J 7.5 Hz, NH), 7.63 (2H, d, J 8.5 Hz, 2H of C6H4CN), 7.50 (2H, d, J 8.0 Hz, 2H of C6H4CN), 4.00 (1H, m, pipH-4), 3.63 (2H, s, CH2C6H4CN), 2.88 (2H, m, 2H of pip), 2.30 (2H, m, 2H of pip), 2.04 (2H, m, 2H of pip), 1.70 (2H, m, 2H of pip); m/z 399, 401 [M+H]+. To a mixture of the 5-bromo-N-(1-(4-cyanobenzyl)piperidin-4-yl)picolinamide (0.040 g, 0.100 mmol, 1.0 eq) 4-(4-piperidinyloxy)benzonitrile (0.024 g, 0.120 mmol, 1.2 eq), sodium t-butoxide (0.019 g, 0.201 mmol, 2.0 eq) and S-Phos (0.004 g, 0.010 mmol, 0.1 eq) was added toluene (1.0 mL). The resulting mixture was degassed by bubbling argon through the mixture.

後処理

  1. custombefore partitioning between EtOAc (120 mL) and water (100 mL)
  2. washThe organics were washed with brine (100 mL), water (100 mL) and brine (100 mL)
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated under reduced pressure

出典と根拠

ORDレコード
ord-4cbcb5ba93b94ceaa67c7f9d64e12f3e
出典データセット
uspto-grants-2016_02
特許番号
US09266856B2

反応ノート

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