Triethylamine → (2R)-N-[(2R)-2-hydroxy-2-(3-pyridinyl)ethyl]-6-iodo-3,4-dihydro-2H-chromene-2-carboxamide

HRID 896864노트

반응식

HRID 896864 반응식
Cl.Cl.[NH2:3][CH2:4][C@@H:5]([C:7]1[CH:8]=[N:9][CH:10]=[CH:11][CH:12]=1)[OH:6].ON1C2C=CC=CC=2N=N1.C(N(CC)CC)C.[I:30][C:31]1[CH:32]=[C:33]2[C:38](=[CH:39][CH:40]=1)[O:37][C@@H:36]([C:41](O)=[O:42])[CH2:35][CH2:34]2>ClCCl>[OH:6][C@H:5]([C:7]1[CH:8]=[N:9][CH:10]=[CH:11][CH:12]=1)[CH2:4][NH:3][C:41]([C@H:36]1[CH2:35][CH2:34][C:33]2[C:38](=[CH:39][CH:40]=[C:31]([I:30])[CH:32]=2)[O:37]1)=[O:42]

참가 물질

6

반응물 4

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 9966213(2R)-6-Iodochromane-2-carboxylic acidHCID 69103521(1R)-2-amino-1-(3-pyridyl)ethanol dihydrochloride

생성물 1

HCID 59118145(2R)-N-[(2R)-2-hydroxy-2-(3-pyridinyl)ethyl]-6-iodo-3,4-dihydro-2H-chromene-2-carboxamide수율 74%

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

(1R)-2-Amino-1-(3-pyridinyl)ethanol dihydrochloride (U.S. Pat. No. 6,051,586) (5.73 g, 27.1 mmol), 1-hydroxybenzotriazole (6.67 g, 49.3 mmol), 1-(3-dimethylaminopropyl)-3-ethylcabodiimide hydrochloride (9.46 g, 49.3 mmol), and triethylamine (13.8 mL, 9.98 g, 98.7 mmol) were added successively to a stirred solution of (2R)-6-iodo-3,4-dihydro-2H-chromene-2-carboxylic acid (Example 7, Method A, 7.50 g, 24.7 mmol) in dichloromethane (100 mL). The reaction was stirred for 18 hours and then diluted with dichloromethane (300 mL). The solution was washed with saturated aqueous sodium bicarbonate (300 mL) and then the aqueous layer was back-extracted with dichloromethane (2×100 mL). The combined organic extracts were washed with brine, dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. Flash chromatography of the residue over silica gel using 5-10% methanol/ethyl acetate gave the product (7.80 g, 74%) as a white solid: 1H NMR (acetone-d6, δ): 8.55 (d, J=1.6 Hz, 1 H), 8.44 (dd, J=4.7, 1.6 Hz, 1 H), 7.71 (ddd, J=7.9, 1.8, 1.8 Hz, 1 H), 7.59 (s, 1 H), 7.35-7.42 (m, 2 H), 7.27 (dd, J=7.9, 4.7 Hz, 1 H), 6.63 (d, 9.6 Hz, 1 H), 4.98 (d, J=4.2 Hz, 1 H), 4.85-4.93 (m, 1 H), 4.53 (dd, J=8.8, 3.4 Hz, 1 H), 3.38-3.70 (m, 2 H), 2.61-2.91 (m, 4 H), 2.16-2.28 (m, 2 H), 1.85-1.99 (m, 1 H); mass spectroscopy gave m/z=425.1 [M+H]+.

후처리

  1. washThe solution was washed with saturated aqueous sodium bicarbonate (300 mL)
  2. extractionthe aqueous layer was back-extracted with dichloromethane (2×100 mL)
  3. washThe combined organic extracts were washed with brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

출처 및 근거

ORD 기록
ord-2aca2dedbcee4bcf966a5280dca8b0ed
출처 데이터셋
uspto-grants-2005_07
특허 번호
US06919371B2

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