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

반응식

HRID 57998 반응식
[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

참가 물질

6

반응물 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

생성물 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

시약·촉매·용매 1

HCID 679Dimethyl Sulfoxide용매

반응 조건

온도
105 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-ee71eea13f904307891ff7f453a0464c
출처 데이터셋
uspto-grants-2016_09
특허 번호
US09434725B2

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