4-Methylmorpholine → 1,5-Dimethyl N-(4-(2-(2-amino-4,7-dihydro-4-oxo-3H-pyrrolo(2,3-d)pyrimidin-5-yl)ethyl)benzoyl)-L-glutamate

HRID 263707

반응식

HRID 263707 반응식
[NH2:1][C:2]1[NH:3][C:4](=[O:22])[C:5]2[C:10]([CH2:11][CH2:12][C:13]3[CH:21]=[CH:20][C:16]([C:17]([OH:19])=O)=[CH:15][CH:14]=3)=[CH:9][NH:8][C:6]=2[N:7]=1.CN1CCOCC1.ClC1C=C(OC)NN(OC)N=1.Cl.[CH3:42][O:43][C:44](=[O:53])[C@H:45]([CH2:47][CH2:48][C:49]([O:51][CH3:52])=[O:50])[NH2:46]>CN(C)C=O>[CH3:42][O:43][C:44](=[O:53])[C@H:45]([CH2:47][CH2:48][C:49]([O:51][CH3:52])=[O:50])[NH:46][C:17](=[O:19])[C:16]1[CH:20]=[CH:21][C:13]([CH2:12][CH2:11][C:10]2[C:5]3[C:4](=[O:22])[NH:3][C:2]([NH2:1])=[N:7][C:6]=3[NH:8][CH:9]=2)=[CH:14][CH:15]=1

참가 물질

6

반응물 4

HCID 79724-Methylmorpholine2회HCID 12917568Dimethyl L-glutamate hydrochlorideHCID 135405776Pemetrexed acidHCID 178491909HCID 178491909, 화합물

생성물 1

HCID 1361208391,5-Dimethyl N-(4-(2-(2-amino-4,7-dihydro-4-oxo-3H-pyrrolo(2,3-d)pyrimidin-5-yl)ethyl)benzoyl)-L-glutamate수율 43%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

To 2.00 g (6.74 mmol) of 4-[2-(2-amino-4,7-dihydro-4-oxo-3H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoic acid, prepared in Preparation 4, in 23 ml dimethylformamide under nitrogen was added 1.40 g (13.8 mmol) of N-methylmorpholine and 1.17 g (6.70 mmol) of 4-chloro-2,6-dimethoxytriazine. The formation of the active ester was monitored by the HPLC analysis of aliquots. After 40 minutes at room temperature 0.70 g (6.9 mmol) of N-methylmorpholine was added followed by 1.56 g (7.37 mmol) L-glutamic acid dimethyl ester hydrochloride. After 30 minutes HPLC analysis indicated substantially complete consumption of the active ester and formation of N-[4-[2-[2-Amino-4,7-dihydro-4-oxo-3H-pyrrolo[2,3-d]pyrimidin-5-yl]ethyl]benzoyl]glutamic acid dimethyl ester. The reaction mixture was filtered and the above product concentrated and purified by silica chromatography (elution 1:4 methanol:methylene chloride). The pure fractions were pooled and provided 1.30 g of the above product in a yield of 43 percent. 1H NMR (DMSO-d6) δ2.01 (m, 2H), 2.40 (t, J=7.4 Hz, 2H), 2.80 (m, 2H), 2.92 (m, 2H), 3.53 (s, 3H), 3.59 (s, 3H), 4.40 (m, 1H), 5.99 (s, 2H),6.26 (d, J=1.9 Hz, 1H), 7.23 (d, J=8.2 Hz, 2H), 7.73 (d, J=8.2 Hz, 2H), 8.62 (d, J=7.5 Hz, 1H), 10.15 (s, 1H), 10.57 (d, J=1.9 Hz, 1H).

후처리

  1. customconsumption of the active ester and formation of N-[4-[2-[2-Amino-4,7-dihydro-4-oxo-3H-pyrrolo[2,3-d]pyrimidin-5-yl]ethyl]benzoyl]glutamic acid dimethyl ester
  2. filtrationThe reaction mixture was filtered
  3. concentrationthe above product concentrated
  4. custompurified by silica chromatography (elution 1:4 methanol:methylene chloride)

출처 및 근거

ORD 기록
ord-f2a901ff654e402a8fae625acc8577fc
출처 데이터셋
uspto-grants-1997_07
특허 번호
US05644058

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