Sodium Chloride → (1-{[(2-chloro-4-pyrimidinyl)oxy]methyl}cyclobutyl)methyl (1S)-1-(1-hydroxy-2-oxo-2-{[(1R)-1-phenylethyl]amino}ethyl)pentylcarbamate

HRID 1180774

반응식

HRID 1180774 반응식
[Cl:1][C:2]1[N:7]=[C:6]([O:8][CH2:9][C:10]2([CH2:14][OH:15])[CH2:13][CH2:12][CH2:11]2)[CH:5]=[CH:4][N:3]=1.[C:16](Cl)(Cl)=[O:17].[NH2:20][C@@H:21]([CH2:35][CH2:36][CH2:37][CH3:38])[CH:22]([OH:34])[C:23]([NH:25][C@@H:26]([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[CH3:27])=[O:24].C(N(CC)C(C)C)(C)C.[Cl-].[Na+]>ClCCl.C1(C)C=CC=CC=1.O1CCCC1.C(OCC)(=O)C>[OH:34][CH:22]([C@@H:21]([NH:20][C:16](=[O:17])[O:15][CH2:14][C:10]1([CH2:9][O:8][C:6]2[CH:5]=[CH:4][N:3]=[C:2]([Cl:1])[N:7]=2)[CH2:13][CH2:12][CH2:11]1)[CH2:35][CH2:36][CH2:37][CH3:38])[C:23](=[O:24])[NH:25][C@@H:26]([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[CH3:27]

참가 물질

10

반응물 5

HCID 5234Sodium ChlorideHCID 6371PhosgeneHCID 81531DiisopropylethylamineHCID 11265560(3S)-3-amino-2-hydroxy-N-[(1R)-1-phenylethyl]heptanamideHCID 11413552(1-{[(2-Chloro-4-pyrimidinyl)oxy]methyl}cyclobutyl)methanol

생성물 1

HCID 11489253(1-{[(2-chloro-4-pyrimidinyl)oxy]methyl}cyclobutyl)methyl (1S)-1-(1-hydroxy-2-oxo-2-{[(1R)-1-phenylethyl]amino}ethyl)pentylcarbamate수율 828.5%

시약·촉매·용매 4

HCID 1140Toluene용매HCID 6344Dichloromethane용매HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매

실험 절차

To a solution of 0.106 g (0.05 mmol) of (1-{[(2-chloro-4-pyrimidinyl)oxy]methyl}cyclobutyl)methanol in 2 mL of dichloromethane cooled to 0° C. was added a 1.0 M solution of 0.937 mL (0.75 mmol) of phosgene in toluene and the contents stirred for 16 h. The reaction mixture was concentrated and the residue was dissolved in 4 mL of tetrahydrofuran and added to a 0° C. solution of 0.132 g (0.50 mmol) of (3S)-3-amino-2-hydroxy-N-[(1R)-1-phenylethyl]heptanamide and 0.259 mL (1.5 mmol) of N,N-diisopropylethylamine in 2 mL of tetrahydrofuran. After stirring for 5 h, ethyl acetate and saturated sodium chloride were added. The organic phase was isolated, dried using magnesium sulfate, concentrated under vacuum, and the residue was purified by silica gel chromatography eluting with ethyl acetate:hexane (7:3) to afford 0.215 g (89%) of (1-{[(2-chloro-4-pyrimidinyl)oxy]methyl}cyclobutyl)methyl (1S)-1-(1-hydroxy-2-oxo-2-{[(1R)-1-phenylethyl]amino}ethyl)pentylcarbamate as a colorless oil. 1H NMR (300 MHz, CDCl3) δ 8.29 (d, J=6 Hz, 1H), 7.32-7.10 (m, 6H), 6.67 (d, J=6 Hz, 1H), 5.61-5.53 (m, 1H), 5.13-5.08 (m, 1H), 4.79, 4.89 (2d, J=5, 6 Hz, 1H), 4.36, 4.39 (2s, 2H), 4.38-4.18 (m, 3H), 3.84 (m, 1H), 2.07-1.50 (m, 10 H), 1.47-1.26 (m, 5H), 0.88 (m, 3H). LC-MS m/z 519 (M+H).

후처리

  1. concentrationThe reaction mixture was concentrated
  2. dissolutionthe residue was dissolved in 4 mL of tetrahydrofuran
  3. stirringAfter stirring for 5 h
  4. customThe organic phase was isolated
  5. customdried
  6. concentrationconcentrated under vacuum
  7. customthe residue was purified by silica gel chromatography
  8. washeluting with ethyl acetate:hexane (7:3)

출처 및 근거

ORD 기록
ord-a7ca0f1c4b104f2aa1806a97b1e03648
출처 데이터셋
uspto-grants-2007_10
특허 번호
US07282512B2

연결된 노트

불러오는 중…