Maleic Anhydride → HCID 178498080, 화합물

HRID 2095170노트

반응식

HRID 2095170 반응식
Cl.[CH3:2][O:3][C:4](=[O:10])[C@@H:5]1[CH2:9][CH2:8][CH2:7][NH:6]1.C(N(CC)CC)C.[C:18]1(=[O:24])O[C:21](=[O:22])[CH:20]=[CH:19]1.ON1C(=O)CCC1=O.C1CCC(N=C=NC2CCCCC2)CC1.[NH2:48][CH2:49][C:50]1[C:51](=[N:56][NH:57][C:58]2[CH:63]=[CH:62][CH:61]=[C:60]([F:64])[CH:59]=2)[C:52]([NH2:55])=[N:53][N:54]=1>COCCOC.C(OCC)C.CN(C=O)C>[CH3:2][O:3][C:4]([CH:5]1[CH2:9][CH2:8][CH2:7][N:6]1[C:18](=[O:24])[CH:19]=[CH:20][C:21](=[O:22])[NH:48][CH2:49][C:50]1[C:51](=[N:56][NH:57][C:58]2[CH:63]=[CH:62][CH:61]=[C:60]([F:64])[CH:59]=2)[C:52]([NH2:55])=[N:53][N:54]=1)=[O:10]

참가 물질

10

반응물 6

HCID 7923Maleic AnhydrideHCID 8471Triethylamine2회HCID 10868DicyclohexylcarbodiimideHCID 80170N-HydroxysuccinimideHCID 2733200methyl L-prolinate hydrochlorideHCID 178510679HCID 178510679, 화합물

생성물 1

HCID 178498080HCID 178498080, 화합물수율 38%

시약·촉매·용매 3

HCID 3283Diethyl Ether용매HCID 6228Dimethylformamide용매HCID 80711,2-Dimethoxyethane용매2회

실험 절차

To a suspension of L-proline methyl ester hydrochloride (200 mg, 1.21 mmole) in 8 mL of ethylene glycol dimethyl ether was added triethylamine (244 mg, 2.4 mmole). The white cloudy mixture was stirred at ambient temperature for 20 min, and was then treated with maleic anhydride in 1 mL of diethyl ether. After 1 hour, the reaction mixture was filtered. The filtrate was mixed with a solution of N-hydroxysuccinimide (172 mg, 1.5 mmole) in ethylene glycol dimethyl ether, and then DCC (412 mg, 2 mmole) was added. The reaction mixture was stirred at ambient temperature overnight. After filtration, the solution of the NHS ester was added in 4 mL portions to a solution of 5-(aminomethyl)-4-(3-fluorophenylhydrazono)-3-amino-4H-pyrazole (60 mg, 0.25 mmole) and triethylamine (0.51 mmole, 52 mg) in 4 mL of DMF at 45° C. After stirring at ambient temperature for 45 minutes, the reaction was quenched by the addition of saline and ethyl acetate. The ethyl acetate extracts were concentrated and the resulting crude material was purified by preparative TLC (CH2Cl2:CH3OH=12:1) to yield 44 mg (38%) of the title compound as a yellow powder. MS (m/z, ES+): 444 (M+1, 56%), 445 (M+2, 13%); 1H NMR (ppm, 300 MHz, DMSO-d6) δ 11.92 (br s, 1H), 8.80 (br s, 1H), 7.35-7.62 (m, 3H), 7.10 (d, J=14.8 Hz, 1H), 7.09 (br s, NH2), 6.90 (d, J=14.8 Hz, 1H), 4.56 (dd, J=8.5 Hz, 1H), 4.36 (dd, J=8.5, 4.0 Hz, 1H), 3.66 (m, 1H), 3.60 (s, OCH3), 3.45 (m, 1H), 3.34 (m, 1H), 2.17 (m, 1H), 1.75-2.00 (m, 3H).

후처리

  1. waitAfter 1 hour
  2. filtrationthe reaction mixture was filtered
  3. stirringThe reaction mixture was stirred at ambient temperature overnight
  4. filtrationAfter filtration
  5. stirringAfter stirring at ambient temperature for 45 minutes
  6. customthe reaction was quenched by the addition of saline and ethyl acetate
  7. concentrationThe ethyl acetate extracts were concentrated
  8. customthe resulting crude material was purified by preparative TLC (CH2Cl2:CH3OH=12:1)

출처 및 근거

ORD 기록
ord-2a35f2c2381c46a6bc37fb3e78aea041
출처 데이터셋
uspto-grants-2013_05
특허 번호
US08445694B2

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