Water → (S)-(1-(6-(1-(6-(piperazin-1-yl)pyridin-2-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl)pyrazin-2-yl)pyrrolidin-2-yl)methanol dihydrochloride

HRID 57998

反応式

HRID 57998 の反応式
[NH:1]1[CH2:5][CH2:4][CH2:3][C@H:2]1[CH2:6][OH:7].[Cl:8][C:9]1[N:14]=[C:13]([C:15]2[N:20]=[CH:19][C:18]3[CH:21]=[N:22][N:23]([C:24]4[N:29]=[C:28]([N:30]5[CH2:35][CH2:34][N:33](C(OC(C)(C)C)=O)[CH2:32][CH2:31]5)[CH:27]=[CH:26][CH:25]=4)[C:17]=3[CH:16]=2)[CH:12]=[N:11][CH:10]=1.[F-].[Cs+].O>CS(C)=O>[ClH:8].[ClH:8].[N:30]1([C:28]2[N:29]=[C:24]([N:23]3[C:17]4[CH:16]=[C:15]([C:13]5[N:14]=[C:9]([N:1]6[CH2:5][CH2:4][CH2:3][C@H:2]6[CH2:6][OH:7])[CH:10]=[N:11][CH:12]=5)[N:20]=[CH:19][C:18]=4[CH:21]=[N:22]3)[CH:25]=[CH:26][CH:27]=2)[CH2:31][CH2:32][NH:33][CH2:34][CH2:35]1

参加物

6

反応物 4

HCID 962WaterHCID 25953Cesium fluorideHCID 640091L-ProlinolHCID 86707183tert-butyl 4-(6-(6-(6-chloropyrazin-2-yl)-1H-pyrazolo[4,3-c]pyridin-1-yl)pyridin-2-yl)piperazine-1-carboxylate

生成物 1

HCID 86707185(S)-(1-(6-(1-(6-(piperazin-1-yl)pyridin-2-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl)pyrazin-2-yl)pyrrolidin-2-yl)methanol dihydrochloride

試薬・触媒・溶媒 1

HCID 679Dimethyl Sulfoxide溶媒

反応条件

温度
105 °C

実験手順

A mixture of 3-5 eq. of (S)-pyrrolidin-2-ylmethanol, 1 eq. of tert-butyl 4-(6-(6-(6-chloropyrazin-2-yl)-1H-pyrazolo[4,3-c]pyridin-1-yl)pyridin-2-yl)piperazine-1-carboxylate, 6-10 eq of cesium fluoride in DMSO was heated at 105° C. for 12-24 hours. The mixture was mixed with water and extracted with ethyl acetate. The organic extracts were washed with water, brine, dried over sodium sulfate and concentrated in vacuum. The crude products were purified on a silica gel column eluting with gradient of ethyl acetate in heptane or DCM. The Boc group was deprotected with 4 M HCl in dioxane in methanol. The crude product was collected by filtration, dissolved in water and lyophilized to give 280. 1H NMR (400 MHz, DMSO-d6) δ 9.37 (s, 1H), 9.31-9.19 (m, 2H), 9.10 (s, 1H), 8.80 (s, 1H), 8.73 (s, 1H), 8.19 (s, 1H), 7.89 (t, J=8.1 Hz, 1H), 7.35 (d, J=7.8 Hz, 1H), 6.97 (d, J=8.5 Hz, 1H), 4.21 (d, J=6.0 Hz, 1H), 3.93 (t, J=5.3 Hz, 4H), 3.58 (m, 1H), 3.49 (m, 2H), 3.22 (d, J=5.4 Hz, 4H), 2.06 (m, 4H). MS (ESI) m/z: 458.3.

後処理

  1. extractionextracted with ethyl acetate
  2. washThe organic extracts were washed with water, brine
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated in vacuum
  5. customThe crude products were purified on a silica gel column
  6. washeluting with gradient of ethyl acetate in heptane or DCM
  7. filtrationThe crude product was collected by filtration
  8. dissolutiondissolved in water

出典と根拠

ORDレコード
ord-ee71eea13f904307891ff7f453a0464c
出典データセット
uspto-grants-2016_09
特許番号
US09434725B2

関連ノート

読み込み中…