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Ammonia → 2-(6-((3aR,6aS)-5-(2-hydroxyethyl)hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)pyridazin-3-yl)-5-(1H-pyrazol-4-yl)phenol

HRID 1027307
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HRID 1027307 반응식
[Si]([O:8][CH2:9][CH2:10][N:11]1[CH2:15][C@@H:14]2[CH2:16][N:17]([C:19]3[N:24]=[N:23][C:22]([C:25]4[CH:30]=[CH:29][C:28]([C:31]5[CH:32]=[N:33][NH:34][CH:35]=5)=[CH:27][C:26]=4[OH:36])=[CH:21][CH:20]=3)[CH2:18][C@@H:13]2[CH2:12]1)(C(C)(C)C)(C)C.Cl.N>O1CCOCC1.CO>[OH:8][CH2:9][CH2:10][N:11]1[CH2:12][C@@H:13]2[CH2:18][N:17]([C:19]3[N:24]=[N:23][C:22]([C:25]4[CH:30]=[CH:29][C:28]([C:31]5[CH:35]=[N:34][NH:33][CH:32]=5)=[CH:27][C:26]=4[OH:36])=[CH:21][CH:20]=3)[CH2:16][C@@H:14]2[CH2:15]1
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참가 물질

6

반응물 3

HCID 222AmmoniaHCID 313Hydrochloric AcidHCID 136377186HCID 136377186, 화합물

생성물 1

HCID 1363771872-(6-((3aR,6aS)-5-(2-hydroxyethyl)hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)pyridazin-3-yl)-5-(1H-pyrazol-4-yl)phenol수율 41%

시약·촉매·용매 2

HCID 887Methanol용매
HCID 31275
1,4-Dioxane
용매
2회

실험 절차

To a solution of 2-(6-((3aR,6aS)-5-(2-((tert-butyldimethylsilyl)oxy)ethyl)hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)pyridazin-3-yl)-5-(1H-pyrazol-4-yl)phenol (20 mg, 0.039 mmol) in dioxane (2 mL) was added 4N HCl in dioxane (1 mL, 4.00 mmol). The reaction mixture was stirred at RT overnight, then basified with 2N NH3 in MeOH and concentrated. The crude product was purified via preparative HPLC to give an off-white solid 2-(6-((3aR,6aS)-5-(2-hydroxyethyl)hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)pyridazin-3-yl)-5-(1H-pyrazol-4-yl)phenol (6.5 mg, 0.016 mmol, 41% yield). LCMS Rt=0.87 min [Method Q]; MS (M+1)=393.1. 1H NMR (400 MHz, METHANOL-d4) δ ppm 8.01 (d, J=9.60 Hz, 1H), 7.93 (s, 2H), 7.69 (d, J=8.08 Hz, 1H), 7.08-7.19 (m, 3H), 3.67-3.77 (m, 4H), 3.56 (d, J=11.12 Hz, 2H), 3.11 (br. s., 2H), 2.97-3.05 (m, 2H), 2.72 (t, J=5.81 Hz, 2H), 2.63-2.70 (m, 2H).

후처리

  1. concentrationconcentrated
  2. customThe crude product was purified via preparative HPLC

출처 및 근거

ORD 기록
ord-4ca9443b79ad41f492ffb3eb3090cb07
출처 데이터셋
uspto-grants-2014_05
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08729263B2

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