Hydrochloric Acid → (S)-4-methyl-2-(1-oxo-4-trifluoromethyl-1,3-dihydro-isoindol-2-yl)-pentanoic acid [5-((S)-1,2-dihydroxy-ethyl)-pyrazin-2-yl]-amide

HRID 2365748노트

반응식

HRID 2365748 반응식
CC1(C)[O:6][C@@H:5]([C:7]2[N:8]=[CH:9][C:10]([NH:13][C:14](=[O:34])[C@@H:15]([N:20]3[CH2:28][C:27]4[C:22](=[CH:23][CH:24]=[CH:25][C:26]=4[C:29]([F:32])([F:31])[F:30])[C:21]3=[O:33])[CH2:16][CH:17]([CH3:19])[CH3:18])=[N:11][CH:12]=2)[CH2:4][O:3]1.Cl>O1CCCC1>[OH:6][C@@H:5]([C:7]1[N:8]=[CH:9][C:10]([NH:13][C:14](=[O:34])[C@@H:15]([N:20]2[CH2:28][C:27]3[C:22](=[CH:23][CH:24]=[CH:25][C:26]=3[C:29]([F:32])([F:30])[F:31])[C:21]2=[O:33])[CH2:16][CH:17]([CH3:19])[CH3:18])=[N:11][CH:12]=1)[CH2:4][OH:3]

참가 물질

4

반응물 2

HCID 313Hydrochloric AcidHCID 86673402(S)-4-methyl-2-(1-oxo-4-trifluoromethyl-1,3-dihydro-isoindol-2-yl)-pentanoic acid [5-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl)-pyrazin-2-yl]-amide

생성물 1

HCID 70674680(S)-4-methyl-2-(1-oxo-4-trifluoromethyl-1,3-dihydro-isoindol-2-yl)-pentanoic acid [5-((S)-1,2-dihydroxy-ethyl)-pyrazin-2-yl]-amide수율 88%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

A solution of afford (S)-4-methyl-2-(1-oxo-4-trifluoromethyl-1,3-dihydro-isoindol-2-yl)-pentanoic acid [5-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl)-pyrazin-2-yl]-amide (53 mg, 0.11 mmol) in tetrahydrofuran (1 mL) was treated with a 1N aqueous hydrochloric acid solution (1 mL) and stirred at room temperature overnight. The reaction mixture was then concentrated in vacuo to remove the tetrahydrofuran and the remaining material was partitioned between ethyl acetate and a saturated aqueous sodium bicarbonate solution. The organic layer was separated and dried over magnesium sulfate, filtered to remove the drying agent and the filtrate concentrated in vacuo to afford (S)-4-methyl-2-(1-oxo-4-trifluoromethyl-1,3-dihydro-isoindol-2-yl)-pentanoic acid [5-((S)-1,2-dihydroxy-ethyl)-pyrazin-2-yl]-amide (43 mg, 88%) as a cream colored foam: [α]29D=+22.9° (c=0.14, methanol); HR-ES(+) m/e calcd for C21H23N4O4F3 [M+H]+ 453.1744, observed 453.1744; 1H NMR (400 MHz, DMSO-d6) δ 11.26 (s, 1H), 9.16 (s, 1H), 8.45 (d, J=1.07 Hz, 1H), 8.02 (dd, J=7.67, 11.29 Hz, 2H), 7.67-7.85 (m, 1H), 5.55 (d, J=4.90 Hz, 1H), 5.28 (dd, J=5.11, 10.65 Hz, 1H), 5.05 (d, J=18.33 Hz, 1H), 4.66-4.78 (m, 2H), 4.62 (q, J=4.90 Hz, 1H), 3.67 (td, J=5.30, 10.92 Hz, 1H), 3.55 (td, J=5.78, 11.24 Hz, 1H), 1.95-2.09 (m, 1H), 1.71-1.88 (m, 1H), 1.49 (br. s., 1H), 0.90-1.00 (m, 6H).

후처리

  1. concentrationThe reaction mixture was then concentrated in vacuo
  2. customto remove the tetrahydrofuran
  3. customthe remaining material was partitioned between ethyl acetate
  4. customThe organic layer was separated
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. customto remove the drying agent
  8. concentrationthe filtrate concentrated in vacuo

출처 및 근거

ORD 기록
ord-406e5736552b42bf88450b4aaa99b220
출처 데이터셋
uspto-grants-2014_04
특허 번호
US08697705B2

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