Sodium Bicarbonate → 3'-Chloro-4-(1,3,5-trimethyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyrazine

HRID 220549ノート

反応式

HRID 220549 の反応式
Cl.Cl.[Cl:3][C:4]1[C:5]([N:10]2[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]2)=[N:6][CH:7]=[CH:8][N:9]=1.[CH3:16][N:17]1[C:21]([CH3:22])=[C:20]([CH:23]=O)[C:19]([CH3:25])=[N:18]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)([O-])O.[Na+]>O1CCCC1>[Cl:3][C:4]1[C:5]([N:10]2[CH2:11][CH2:12][N:13]([CH2:23][C:20]3[C:19]([CH3:25])=[N:18][N:17]([CH3:16])[C:21]=3[CH3:22])[CH2:14][CH2:15]2)=[N:6][CH:7]=[CH:8][N:9]=1

参加物

6

反応物 4

HCID 516892Sodium BicarbonateHCID 7365151,3,5-trimethyl-1H-pyrazole-4-carboxaldehyde2 回HCID 5049666Sodium triacetoxyborohydrideHCID 866416583'-chloro-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl dihydrochloride

生成物 1

HCID 866416593'-Chloro-4-(1,3,5-trimethyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyrazine収率 99%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

To a suspension of 3′-chloro-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl dihydrochloride (2.11 g, 7.77 mmol, 1 eq) in tetrahydrofuran (20 mL) add 1,3,5-trimethyl-1H-pyrazole-4-carbaldehyde (1.61 g, 11.65 mmol, 1.5 eq). Stir for 10 min and add sodium triacetoxyborohydride (4.20 g, 19.40 mmol, 2.5 eq) in one portion. Stir at room temperature under nitrogen for 1 hr., then add additional 1,3,5-trimethyl-1H-pyrazole-4-carbaldehyde (0.50 g, 3.6 mmol, 0.47 eq). Stir for 30 min., add saturated aq. sodium hydrogen carbonate (100 mL) slowly, and then extract with DCM (3×50 mL). Pass the combined DCM extracts through an IST Phase Separator Frit®, concentrate and purify (silica gel chromatography, eluting with 2:98 to 5:95 methanol:DCM), to give 3′-chloro-4-(1,3,5-trimethyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl as a white powder (2.468 g, 98%). MS (ES): m/z=321 [M+H]+.

後処理

  1. stirringStir at room temperature under nitrogen for 1 hr
  2. stirringStir for 30 min.
  3. extractionextract with DCM (3×50 mL)
  4. concentrationconcentrate
  5. custompurify
  6. wash(silica gel chromatography, eluting with 2:98 to 5:95 methanol:DCM)

出典と根拠

ORDレコード
ord-6d50b6a3c555464791c405d2e1c2dac2
出典データセット
uspto-grants-2012_06
特許番号
US08202873B2

反応ノート

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