Sodium Hydroxide → 4-[2-(2-Methyl-2-methyldisulfanyl-propylamino)-ethoxy]-2,6-bis-(hydroxymethyl)-pyridine

HRID 2173748ノート

反応式

HRID 2173748 の反応式
[NH2:1][CH2:2][CH2:3][O:4][C:5]1[CH:10]=[C:9]([CH2:11][OH:12])[N:8]=[C:7]([CH2:13][OH:14])[CH:6]=1.[C:15](OC(NCCOC1C=C(CO)N=C(CO)C=1)=O)([CH3:18])([CH3:17])[CH3:16].[CH3:36][S:37][S:38]C(C)(C)C=O.C([BH3-])#N.[Na+].[OH-].[Na+]>C1COCC1.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-].C(O)C>[CH3:16][CH:15]([CH3:18])[CH2:17][N:1]([S:38][S:37][CH3:36])[CH2:2][CH2:3][O:4][C:5]1[CH:6]=[C:7]([CH2:13][OH:14])[N:8]=[C:9]([CH2:11][OH:12])[CH:10]=1

参加物

9

反応物 5

HCID 14798Sodium HydroxideHCID 1062172-(Methyldithio)isobutyraldehyde2 回HCID 5003444Sodium cyanoborohydride2 回HCID 57570863HCID 57570863、化合物HCID 57570979HCID 57570979、化合物

生成物 1

HCID 871207774-[2-(2-Methyl-2-methyldisulfanyl-propylamino)-ethoxy]-2,6-bis-(hydroxymethyl)-pyridine

試薬・触媒・溶媒 3

HCID 11026Titanium isopropoxide触媒2 回HCID 702Ethanol溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

To a suspension of 390 mg of 4-[2-amino-ethoxy]-2,6-bis-(hydroxymethyl)-pyridine (prepared after deprotection of the boc group of 4-(2-tert-butoxycarbonylamino-ethoxy)-2,6-bis-(hydroxymethyl)-pyridine described on page 101 of WO 07085930) in 2 mL of THF was added 270 μl of 2-(methyldithio)-isobutyraldehyde and 730 μL of titanium isopropoxide. After 20 min, a further 270 μl of 2-(methyldithio)-isobutyraldehyde and 730 μL of titanium isopropoxide were added and the mixture was stirred for 2 hours at room temperature. The mixture was then supplemented with 6 mL of ethanol, stirred for 20 min at room temperature and then supplemented with 124 mg of sodium cyanoborohydride. After stirring for 45 minutes, a further 124 mg of sodium cyanoborohydride were added and after stirring for 1 hour, the mixture was concentrated under reduced pressure, and diluted with EtOAc and water. The resulting precipitate was filtered off, and dissolved in aqueous 1M HCl solution. The aqueous phase obtained was brought to basic pH with aqueous 5M sodium hydroxide solution, extracted 3× with DCM and the combined organic phases were concentrated under reduced pressure. 322 mg of 4-[2-(2-methyl-2-methyldisulfanyl-propylamino)-ethoxy]-2,6-bis-(hydroxymethyl)-pyridine were obtained. 1H NMR (400 MHz, DMSO-d6): 1.26 (s, 6H); 1.81 (broad m, 1H); 2.39 (s, 3H); 2.67 (broad s, 2H); 2.94 (broad t, J=5.7 Hz, 2H); 4.11 (t, J=5.7 Hz, 2H); 4.45 (d, J=5.5 Hz, 4H); 5.32 (t, J=5.5 Hz, 2H); 6.85 (s, 2H). LC/MS (A): tr=0.24 min; [M+H]+: m/z 347.

後処理

  1. stirringstirred for 20 min at room temperature
  2. stirringAfter stirring for 45 minutes
  3. stirringafter stirring for 1 hour
  4. concentrationthe mixture was concentrated under reduced pressure
  5. additiondiluted with EtOAc and water
  6. filtrationThe resulting precipitate was filtered off
  7. dissolutiondissolved in aqueous 1M HCl solution
  8. customThe aqueous phase obtained
  9. extractionextracted 3× with DCM
  10. concentrationthe combined organic phases were concentrated under reduced pressure

出典と根拠

ORDレコード
ord-72de46c9828f4496bc055452411e3a70
出典データセット
uspto-grants-2015_06
特許番号
US09056914B2

反応ノート

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