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Hydrochloric Acid → 2-[4-(2-Chloro-phenylamino)-6-oxo-6h-pyridazin-1-yl]-4-methyl-pentanoic acid [1-((r)-2,3-dihydroxy-propyl)-1h-pyrazol-3-yl]-amide

HRID 2381546
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HRID 2381546 반응식
CC1(C)[O:6][C@H:5]([CH2:7][N:8]2[CH:12]=[CH:11][C:10]([NH:13][C:14](=[O:35])[CH:15]([N:20]3[C:25](=[O:26])[CH:24]=[C:23]([NH:27][C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=4[Cl:34])[CH:22]=[N:21]3)[CH2:16][CH:17]([CH3:19])[CH3:18])=[N:9]2)[CH2:4][O:3]1.Cl>O1CCCC1>[OH:6][C@@H:5]([CH2:4][OH:3])[CH2:7][N:8]1[CH:12]=[CH:11][C:10]([NH:13][C:14](=[O:35])[CH:15]([N:20]2[C:25](=[O:26])[CH:24]=[C:23]([NH:27][C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=3[Cl:34])[CH:22]=[N:21]2)[CH2:16][CH:17]([CH3:19])[CH3:18])=[N:9]1
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4

반응물 2

HCID 313Hydrochloric AcidHCID 668931232-[4-(2-chloro-phenylamino)-6-oxo-6H-pyridazin-1-yl]-4-methyl-pentanoic acid [1-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-1H-pyrazol-3-yl]-amide

생성물 1

HCID 579192422-[4-(2-Chloro-phenylamino)-6-oxo-6h-pyridazin-1-yl]-4-methyl-pentanoic acid [1-((r)-2,3-dihydroxy-propyl)-1h-pyrazol-3-yl]-amide수율 78%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

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온도
25 °C

실험 절차

A solution of 2-[4-(2-chloro-phenylamino)-6-oxo-6H-pyridazin-1-yl]-4-methyl-pentanoic acid [1-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-1H-pyrazol-3-yl]-amide (41.2 mg, 0.08 mmol) in tetrahydrofuran (2 mL) was treated with a 1 M aqueous hydrochloric acid solution (2 mL), and the reaction stirred at 25° C. overnight. At this point, the reaction was dried under nitrogen and suspended in ethyl acetate (20 mL), then washed with a 1:1 aqueous sodium bicarbonate/water solution (20 mL total) and a saturated aqueous sodium chloride solution (10 mL). The organics were dried over sodium sulfate, concentrated in vacuo, and dried from methylene chloride, ethanol, and diethyl ether, and in a vacuum oven at 50° C. for 3 h to afford 2-[4-(2-chloro-phenylamino)-6-oxo-6H-pyridazin-1-yl]-4-methyl-pentanoic acid [1-((R)-2,3-dihydroxy-propyl)-1H-pyrazol-3-yl]-amide as a light yellow solid (29.6 mg, 78%); ES+-HRMS m/e calcd for C22H27N6O4Cl [M+H+] 475.1855 found 475.1855. 1H NMR (300 MHz, DMSO-d6) δ ppm 0.86 (d, J=6.6 Hz, 3H), 0.88 (d, J=6.6 Hz, 3H), 1.44 (br. s., 1H), 1.62-1.81 (m, 1H), 2.00-2.22 (m, 1H), 3.20-3.32 (m, 2H), 3.70-3.92 (m, 2H), 4.08 (dd, J=13.4, 3.8 Hz, 1H), 4.71 (t, J=5.6 Hz, 1H), 4.94 (dd, J=5.1, 1.8 Hz, 1H), 5.49 (dd, J=11.0, 4.1 Hz, 1H), 5.54 (d, J=2.7 Hz, 1H), 6.35 (d, J=2.1 Hz, 1H), 7.28 (td, J=7.8, 1.2 Hz, 1H), 7.40 (td, J=7.8, 1.2 Hz, 1H), 7.47 (dd, J=7.8, 1.2 Hz, 1H), 7.52 (d, J=2.1 Hz, 1H), 7.60 (dd, J=7.8, 1.2 Hz, 1H), 7.86 (d, J=2.7 Hz, 1H), 8.94 (s, 1H), 10.65 (s, 1H).

후처리

  1. customAt this point, the reaction was dried under nitrogen
  2. washwashed with a 1:1 aqueous sodium bicarbonate/water solution (20 mL total)
  3. dry with materialThe organics were dried over sodium sulfate
  4. concentrationconcentrated in vacuo
  5. dry with materialdried from methylene chloride, ethanol, and diethyl ether

출처 및 근거

ORD 기록
ord-b8216088208a49d7a309d9b44b54e098
출처 데이터셋
uspto-grants-2012_09
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08258134B2

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