Hydrochloric Acid → 3-(1-(4-amino-3-(3-fluoro-5-hydroxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-4-(1-(azetidin-3-yl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-isochromen-1-one dihydrochloride

HRID 634507노트

반응식

HRID 634507 반응식
[ClH:1].O1CCOCC1.C(O)=O.[NH2:11][C:12]1[N:17]=[CH:16][N:15]=[C:14]2[N:18]([CH:29]([C:31]3[O:32][C:33](=[O:58])[C:34]4[C:39]([C:40]=3[C:41]3[CH2:46][CH2:45][N:44]([CH:47]5[CH2:50][N:49](C(OC(C)(C)C)=O)[CH2:48]5)[CH2:43][CH:42]=3)=[CH:38][CH:37]=[CH:36][CH:35]=4)[CH3:30])[N:19]=[C:20]([C:21]3[CH:26]=[C:25]([OH:27])[CH:24]=[C:23]([F:28])[CH:22]=3)[C:13]=12>O1CCOCC1CO.C(O)=O.O.CC#N>[ClH:1].[ClH:1].[NH2:11][C:12]1[N:17]=[CH:16][N:15]=[C:14]2[N:18]([CH:29]([C:31]3[O:32][C:33](=[O:58])[C:34]4[C:39]([C:40]=3[C:41]3[CH2:46][CH2:45][N:44]([CH:47]5[CH2:50][NH:49][CH2:48]5)[CH2:43][CH:42]=3)=[CH:38][CH:37]=[CH:36][CH:35]=4)[CH3:30])[N:19]=[C:20]([C:21]3[CH:26]=[C:25]([OH:27])[CH:24]=[C:23]([F:28])[CH:22]=3)[C:13]=12

참가 물질

7

반응물 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 118131307tert-butyl 3-(4-(3-(1-(4-amino-3-(3-fluoro-5-hydroxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-1-oxo-1H-isochromen-4-yl)-5,6-dihydropyridin-1(2 H)-yl)azetidine-1-carboxylate formate

생성물 1

HCID 1181314963-(1-(4-amino-3-(3-fluoro-5-hydroxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-4-(1-(azetidin-3-yl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-isochromen-1-one dihydrochloride수율 91%

시약·촉매·용매 3

HCID 284Formic Acid용매2회HCID 12655091(1,4-Dioxan-2-yl)methanol용매HCID 18373917Acetonitrile--water (1/1)용매2회

실험 절차

4.0 M HCl in 1,4-dioxane (0.5 ml, 2.000 mmol) was added to a solution of tert-butyl 3-(4-(3-(1-(4-amino-3-(3-fluoro-5-hydroxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-1-oxo-1H-isochromen-4-yl)-5,6-dihydropyridin-1(2 H)-yl)azetidine-1-carboxylate formate (70 mg, 0.100 mmol) in 1,4-dioxane-methanol 3:1 (4 ml). The mixture was stirred for 6 hrs at rt, then volatiles were removed under reduced pressure. Purification by RP-flash chromatography (Biotage 30 g C18 column, gradient elution from 100:0 to 60:40 A/B in 15 CV; A: water/MeCN 95/5+0.01% HCOOH, B: water/MeCN 5/95+0.01% HCOOH) yielded title compound (57 mg, 0.091 mmol, 91% yield) as a white powder.

후처리

  1. customvolatiles were removed under reduced pressure
  2. customPurification by RP-flash chromatography (Biotage 30 g
  3. washC18 column, gradient elution from 100:0 to 60:40 A/B in 15 CV

출처 및 근거

ORD 기록
ord-f9b18045c5154229ae9cdb6e06450d2e
출처 데이터셋
uspto-grants-2016_04
특허 번호
US09321776B2

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