Hydrochloric Acid → (R)-2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-hexanoic acid [1-((R)-2,3-dihydroxy-propyl)-1H-pyrazol-3-yl]-amide

HRID 19413노트

반응식

HRID 19413 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])[C@H:15]([N:21]3[CH2:25][C:24]([O:26][C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=4[Cl:33])=[CH:23][C:22]3=[O:34])[CH2:16][CH:17]([CH3:20])[CH2:18][CH3:19])=[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])[C@H:15]([N:21]2[CH2:25][C:24]([O:26][C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=3[Cl:33])=[CH:23][C:22]2=[O:34])[CH2:16][CH:17]([CH3:20])[CH2:18][CH3:19])=[N:9]1

참가 물질

4

반응물 2

HCID 313Hydrochloric AcidHCID 66899124(R)-2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-hexanoic acid [1-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-1H-pyrazol-3-yl]-amide

생성물 1

HCID 66899668(R)-2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-hexanoic acid [1-((R)-2,3-dihydroxy-propyl)-1H-pyrazol-3-yl]-amide수율 90.4%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

A solution of (R)-2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-hexanoic acid [1-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-1H-pyrazol-3-yl]-amide (prepared in Example 252, 600 mg, 1.16 mmol) in tetrahydrofuran (25 mL) was treated with 2N aqueous hydrochloric acid (12 mL) and stirred at room temperature for 2 h. At this time the mixture was concentrated in vacuo and the residue partitioned between 17% ethyl acetate/hexanes and water. The layers were separated and the organic layer was washed with brine and dried with sodium sulfate. The mixture was filtered and concentrated in vacuo which afforded (R)-2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-hexanoic acid [1-((R)-2,3-dihydroxy-propyl)-1H-pyrazol-3-yl]-amide (500 mg, 90.4%) as a fluffy powder: HR-ES-MS (m/z) calculated for C23H29ClN4O5 [M+H]+ 477.1899, observed 477.1896. 1H NMR (300 MHz, DMSO-d6) δ ppm 0.86 (br. s., 3H), 1.29 (br. s., 6H), 1.78 (br. s., 2H), 3.14-3.58 (m, 4H), 3.70-3.93 (m, 2H), 4.09 (dd, J=13.4, 2.6 Hz, 1H), 4.21 (d, J=18.4 Hz, 1H), 4.58 (d, J=18.4 Hz, 1H), 4.69-4.79 (m, 1H), 4.79 (s, 1H), 6.41 (br. s., 1H), 7.37 (t, J=7.2 Hz, 1H), 7.41-7.58 (m, 3H), 7.65 (d, J=7.8 Hz, 1H), 10.70 (br. s., 1H).

후처리

  1. concentrationAt this time the mixture was concentrated in vacuo
  2. customthe residue partitioned between 17% ethyl acetate/hexanes and water
  3. customThe layers were separated
  4. washthe organic layer was washed with brine
  5. dry with materialdried with sodium sulfate
  6. filtrationThe mixture was filtered
  7. concentrationconcentrated in vacuo which

출처 및 근거

ORD 기록
ord-73de2e58f6584063a2e7b1730647fcc8
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07741327B2

반응 노트

불러오는 중…