Hydrochloric Acid → 4-[4-(4-methanesulfonyl-phenoxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid (R)-sec-butyl ester

HRID 1931710

반응식

HRID 1931710 반응식
Cl[C:2](Cl)([O:4]C(=O)OC(Cl)(Cl)Cl)Cl.[CH3:13][C@@H:14]([OH:17])[CH2:15][CH3:16].N1C=CC=CC=1.Cl.FC(F)(F)C(O)=O.[CH3:32][S:33]([C:36]1[CH:57]=[CH:56][C:39]([O:40][C:41]2[N:46]=[CH:45][N:44]=[C:43]3[N:47]([CH:50]4[CH2:55][CH2:54][NH:53][CH2:52][CH2:51]4)[N:48]=[CH:49][C:42]=23)=[CH:38][CH:37]=1)(=[O:35])=[O:34].C(N(C(C)C)CC)(C)C>ClCCCl.O>[C@H:14]([O:17][C:2]([N:53]1[CH2:52][CH2:51][CH:50]([N:47]2[C:43]3=[N:44][CH:45]=[N:46][C:41]([O:40][C:39]4[CH:38]=[CH:37][C:36]([S:33]([CH3:32])(=[O:35])=[O:34])=[CH:57][CH:56]=4)=[C:42]3[CH:49]=[N:48]2)[CH2:55][CH2:54]1)=[O:4])([CH2:15][CH3:16])[CH3:13]

참가 물질

9

반응물 6

HCID 313Hydrochloric AcidHCID 1049PyridineHCID 81531DiisopropylethylamineHCID 84682(-)-2-ButanolHCID 94429TriphosgeneHCID 669153264-(4-methanesulfonyl-phenoxy)-1-piperidin-4-yl-1H-pyrazolo[3,4-d]pyrimidine trifluoroacetate salt2회

생성물 1

HCID 579648874-[4-(4-methanesulfonyl-phenoxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid (R)-sec-butyl ester수율 36.6%

시약·촉매·용매 2

HCID 111,2-Dichloroethane용매HCID 962Water용매

반응 조건

온도
40 °C

실험 절차

Triphosgene (217 mg, 0.73 mmol) was added to a solution of (R)-(−)-2-butanol (Aldrich Chemical Company, Inc., Milwaukee, Wis., USA 148 mg, 2 mmol) in a mixture of pyridine (190 μL, 2.3 mmol) and 1,2-dichloroethane (10 mL). The solution was stirred at 40° C. for 3 h and then cooled to room temperature. 1 M aqueous hydrochloric acid (2.5 mL) and water (3 mL) were added. The layers were separated and the organic phase was dried (magnesium sulfate), filtered, and evaporated. 4-(4-Methanesulfonyl-phenoxy)-1-piperidin-4-yl-1H-pyrazolo[3,4-d]pyrimidine trifluoroacetate salt (Intermediate 27; 220 mg, 0.45 mmol) and diisopropylethylamine (250 μL) were added and the mixture was stirred for 30 min and then chromatographed, eluting with 50-75% ethyl acetate/hexanes, to give 4-[4-(4-methanesulfonyl-phenoxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid (R)-sec-butyl ester (78 mg, 36%) as an off-white foam/solid.

후처리

  1. temperaturecooled to room temperature
  2. customThe layers were separated
  3. dry with materialthe organic phase was dried (magnesium sulfate)
  4. filtrationfiltered
  5. customevaporated
  6. stirringthe mixture was stirred for 30 min
  7. customchromatographed
  8. washeluting with 50-75% ethyl acetate/hexanes

출처 및 근거

ORD 기록
ord-6176f9f9d84f4f64b679d351adaca44f
출처 데이터셋
uspto-grants-2012_05
특허 번호
US08188098B2

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