Ammonia → (3r)-3-[2-Benzyl-6-[(3r,4r)-3,4-difluoropyrrolidine-1-yl]-3-pyridyl]ethynyl-3-quinuclidinol

HRID 1359344ノート

反応式

HRID 1359344 の反応式
[CH2:1]([C:8]1[C:13](I)=[CH:12][CH:11]=[C:10]([N:15]2[CH2:19][C@@H:18]([F:20])[C@H:17]([F:21])[CH2:16]2)[N:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:22]([C@:24]1([OH:32])[CH:29]2[CH2:30][CH2:31][N:26]([CH2:27][CH2:28]2)[CH2:25]1)#[CH:23].C(N(CC)CC)C.N>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CO>[CH2:1]([C:8]1[C:13]([C:23]#[C:22][C@:24]2([OH:32])[CH:29]3[CH2:30][CH2:31][N:26]([CH2:27][CH2:28]3)[CH2:25]2)=[CH:12][CH:11]=[C:10]([N:15]2[CH2:19][C@@H:18]([F:20])[C@H:17]([F:21])[CH2:16]2)[N:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

参加物

7

反応物 4

HCID 222AmmoniaHCID 8471TriethylamineHCID 946095(3R)-3-ethynyl-1-azabicyclo[2.2.2]octan-3-olHCID 697590462-benzyl-6-[(3R,4R)-3,4-difluoropyrrolidine-1-yl]-3-iodopyridine

生成物 1

HCID 59077824(3r)-3-[2-Benzyl-6-[(3r,4r)-3,4-difluoropyrrolidine-1-yl]-3-pyridyl]ethynyl-3-quinuclidinol収率 40.4%

試薬・触媒・溶媒 2

HCID 178418397HCID 178418397、化合物触媒HCID 887Methanol溶媒

反応条件

温度
75 °C

実験手順

A mixture of 152 mg of 2-benzyl-6-[(3R,4R)-3,4-difluoropyrrolidine-1-yl]-3-iodopyridine, 60 mg of (3R)-3-ethynyl-3-quinuclidinol, 22 mg of tetrakis(triphenylphosphine)palladium(0), 7 mg of cuprous iodide, 106 μl of triethylamine and 1.5 ml of methanol was heated under stirring for 3 hours at 75° C. in a nitrogen atmosphere. The reaction solution was poured into an aqueous dilute ammonia and then extracted with ethyl acetate. The extract was washed with brine and the solvent was removed. The residue was subjected to NH-silica gel (Fuji Silicia) column chromatography, eluted with hexane/ethyl acetate (1:1) and then with ethyl acetate/methanol (15:1) and crystallized from hexane/ethyl acetate, to give 65 mg of the target compound.

後処理

  1. temperaturewas heated
  2. extractionextracted with ethyl acetate
  3. washThe extract was washed with brine
  4. customthe solvent was removed
  5. washeluted with hexane/ethyl acetate (1:1)
  6. customwith ethyl acetate/methanol (15:1) and crystallized from hexane/ethyl acetate

出典と根拠

ORDレコード
ord-eb90d345477c41f7823cd30dd8ae279d
出典データセット
uspto-grants-2003_07
特許番号
US06599917B1

反応ノート

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