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Hydrogen Peroxide → 5-((2R,4S)-4-carbamoyl-2-(3-fluorophenyl)pyrrolidin-1-yl)-N,N-bis(4-methoxybenzyl)pyrazolo[1,5-a]pyridine-3-carboxamide

HRID 513056
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HRID 513056 반응식
[C:1]([C@@H:3]1[CH2:7][N:6]([C:8]2[CH:13]=[CH:12][N:11]3[N:14]=[CH:15][C:16]([C:17]([N:19]([CH2:29][C:30]4[CH:35]=[CH:34][C:33]([O:36][CH3:37])=[CH:32][CH:31]=4)[CH2:20][C:21]4[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][CH:22]=4)=[O:18])=[C:10]3[CH:9]=2)[C@@H:5]([C:38]2[CH:43]=[CH:42][CH:41]=[C:40]([F:44])[CH:39]=2)[CH2:4]1)#[N:2].[OH-:45].[Na+].OO>CO>[C:1]([C@@H:3]1[CH2:7][N:6]([C:8]2[CH:13]=[CH:12][N:11]3[N:14]=[CH:15][C:16]([C:17]([N:19]([CH2:29][C:30]4[CH:35]=[CH:34][C:33]([O:36][CH3:37])=[CH:32][CH:31]=4)[CH2:20][C:21]4[CH:22]=[CH:23][C:24]([O:27][CH3:28])=[CH:25][CH:26]=4)=[O:18])=[C:10]3[CH:9]=2)[C@@H:5]([C:38]2[CH:43]=[CH:42][CH:41]=[C:40]([F:44])[CH:39]=2)[CH2:4]1)(=[O:45])[NH2:2]
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참가 물질

5

반응물 3

HCID 784Hydrogen PeroxideHCID 14798Sodium HydroxideHCID 682824635-((2R,4S)-4-cyano-2-(3-fluorophenyl)pyrrolidin-1-yl)-N,N-bis(4-methoxybenzyl)pyrazolo[1,5-a]pyridine-3-carboxamide

생성물 1

HCID 682821825-((2R,4S)-4-carbamoyl-2-(3-fluorophenyl)pyrrolidin-1-yl)-N,N-bis(4-methoxybenzyl)pyrazolo[1,5-a]pyridine-3-carboxamide

시약·촉매·용매 1

HCID 887
Methanol
용매

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온도
0 °C

실험 절차

A solution of 5-((2R,4S)-4-cyano-2-(3-fluorophenyl)pyrrolidin-1-yl)-N,N-bis(4-methoxybenzyl)pyrazolo[1,5-a]pyridine-3-carboxamide (I-35) (25 mg, 0.042 mmol) in MeOH (1 mL) was cooled to 0° C. A 1M NaOH solution (0.17 mL, 0.17 mmol) and 30% H2O2 (0.01 mL) were added to the reaction and stirred at 0° C. for 1 hour followed by room temperature for 1 hour. The reaction was concentrated to dryness and the residue was partitioned between EtOAc and H2O. The aqueous layer was extracted twice with EtOAc and the combined organics were dried over Na2SO4, filtered, and concentrated. The residue was purified by silica chromatography with EtOAc/hexane gradient as eluent to yield 5-((2R,4S)-4-carbamoyl-2-(3-fluorophenyl)pyrrolidin-1-yl)-N,N-bis(4-methoxybenzyl)pyrazolo[1,5-a]pyridine-3-carboxamide (I-54). 1H NMR (400 MHz, CDCl3) δ 8.09 (d, J=7.7 Hz, 1 H), 7.78 (s, 1 H), 7.32-7.27 (m, 1H), 7.18 (d, J=8.5 Hz, 4 H), 7.14-7.09 (m, 1 H), 7.00-6.92 (m, 2 H), 6.89 (d, J=8.6 Hz, 4 H), 6.85 (s, 1 H), 6.15 (dd, J=2.7, 7.6 Hz, 1 H), 5.75 (bs, 1 H), 5.54 (bs, 1 H), 5.05 (d, J=7.7 Hz, 1 H), 4.72 (d, J=15.7 Hz, 2 H), 4.51 (d, J=15.8 Hz, 2 H), 4.04-3.97 (m, 1H), 3.88-3.82 (m, 1 H), 3.81 (s, 6 H), 3.23-3.11 (m, 1 H), 2.87-2.73 (m, 1 H), 2.19 (ddd, J=1.4, 6.5, 12.3 Hz, 1 H). MS m/z 608.3 (M+1)+.

후처리

  1. waitfollowed by room temperature for 1 hour
  2. concentrationThe reaction was concentrated to dryness
  3. customthe residue was partitioned between EtOAc and H2O
  4. extractionThe aqueous layer was extracted twice with EtOAc
  5. dry with materialthe combined organics were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by silica chromatography with EtOAc/hexane gradient as eluent

출처 및 근거

ORD 기록
ord-e788eaf700ca422eb0204ac819964154
출처 데이터셋
uspto-grants-2015_08
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09102671B2

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