Hexachloroethane → 3-(4-Aza-spiro[2.5]oct-4-yl)-6-fluoro-[1,2,4]triazolo[4,3-a]pyridine

HRID 1402413ノート

反応式

HRID 1402413 の反応式
[F:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][NH:9][C:10]([N:12]2[CH2:19][CH2:18][CH2:17][CH2:16][C:13]32[CH2:15][CH2:14]3)=O)=[N:6][CH:7]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(N(CC)CC)C.ClC(Cl)(Cl)C(Cl)(Cl)Cl>O1CCOCC1>[CH2:15]1[C:13]2([CH2:16][CH2:17][CH2:18][CH2:19][N:12]2[C:10]2[N:6]3[CH:7]=[C:2]([F:1])[CH:3]=[CH:4][C:5]3=[N:8][N:9]=2)[CH2:14]1

参加物

6

反応物 4

HCID 6214HexachloroethaneHCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 866872644-Aza-spiro[2,5]octane-4-carboxylic acid N'-(5-fluoro-pyridin-2-yl)-hydrazide

生成物 1

HCID 866872653-(4-Aza-spiro[2.5]oct-4-yl)-6-fluoro-[1,2,4]triazolo[4,3-a]pyridine収率 82%

試薬・触媒・溶媒 1

HCID 312751,4-Dioxane溶媒

実験手順

To a solution of Intermediate 148b (587 mg, 2.22 mmol), triphenyl phosphine (1.17 g, 4.44 mmol) and triethylamine (1.24 mL, 8.88 mmol) in dioxane (25 mL) at RT was added hexachloroethane (1.05 g, 4.44 mmol). The resulting opaque solution was stirred at RT for 30 min, and at reflux for 16 h. The cooled solution was filtered, and the filter-cake washed with THF (5 mL). The combined organics were applied to an SCX-2 cartridge, which was washed with MeOH (100 mL). The product was eluted with 2M NH3 in MeOH (75 mL); concentration in vacuo left a brown oil. Flash chromatography (silica 40 g, 1.5-4.5% MeOH in DCM) gave the title compound as a brown gum (82%). LCMS (Method 3): Rt 2.92 min, m/z 247 [MH+].

後処理

  1. temperatureat reflux for 16 h
  2. filtrationThe cooled solution was filtered
  3. washthe filter-cake washed with THF (5 mL)
  4. washwas washed with MeOH (100 mL)
  5. washThe product was eluted with 2M NH3 in MeOH (75 mL)
  6. concentrationconcentration in vacuo
  7. waitleft a brown oil

出典と根拠

ORDレコード
ord-dd0ee8448ec24bbf8678b9a6a5db051d
出典データセット
uspto-grants-2014_12
特許番号
US08907094B2

反応ノート

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