Ammonia → (3R)-3-[2-Benzyl-6-[(3R,4S)-3-(fluoromethoxy)-4-methoxypyrrolidine-1-yl]-3-pyridyl]ethynyl-3-quinuclidinol

HRID 1359348ノート

反応式

HRID 1359348 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]([O:20][CH3:21])[C@H:17]([O:22][CH2:23][F:24])[CH2:16]2)[N:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:25]([C@:27]1([OH:35])[CH:32]2[CH2:33][CH2:34][N:29]([CH2:30][CH2:31]2)[CH2:28]1)#[CH:26].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.CN(C)C=O>[CH2:1]([C:8]1[C:13]([C:26]#[C:25][C@:27]2([OH:35])[CH:32]3[CH2:33][CH2:34][N:29]([CH2:30][CH2:31]3)[CH2:28]2)=[CH:12][CH:11]=[C:10]([N:15]2[CH2:19][C@H:18]([O:20][CH3:21])[C@H:17]([O:22][CH2:23][F:24])[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 697586932-benzyl-6-[(3R,4S)-3-(fluoromethoxy)-4-methoxypyrrolidine-1-yl]-3-iodopyridine

生成物 1

HCID 69759259(3R)-3-[2-Benzyl-6-[(3R,4S)-3-(fluoromethoxy)-4-methoxypyrrolidine-1-yl]-3-pyridyl]ethynyl-3-quinuclidinol収率 71.4%

試薬・触媒・溶媒 2

HCID 178418397HCID 178418397、化合物触媒HCID 6228Dimethylformamide溶媒

反応条件

温度
75 °C

実験手順

A mixture of 43.9 mg of 2-benzyl-6-[(3R,4S)-3-(fluoromethoxy)-4-methoxypyrrolidine-1-yl]-3-iodopyridine, 16.5 mg of (3R)-3-ethynyl-3-quinuclidinol, 11.5 mg of tetrakis(triphenylphosphine)palladium(0), 0.9 mg of cuprous iodide, 42 μl of triethylamine and 3.0 ml of N,N-dimethylformamide was heated under stirring for 1 hours at 75° C. in a nitrogen atmosphere. The reaction solution was poured into an aqueous dilute ammonia, and then the mixture was extracted with ethyl acetate. The organic phase was washed with brine and the solvent was removed. The residue was subjected to NH-silica gel (Fuji Silicia) column chromatography and eluted with hexane/ethyl acetate (1:1) and then with ethyl acetate/methanol (15:1), to give 33 mg of the target compound.

後処理

  1. temperaturewas heated
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe organic phase was washed with brine
  4. customthe solvent was removed
  5. washeluted with hexane/ethyl acetate (1:1)

出典と根拠

ORDレコード
ord-bd4495aabf03451da5520eebaebf52bd
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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