4-Methylmorpholine → (S)-4-(4-(2-(2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl)benzamido)-5-(benzyloxy)-5-oxopentanoic acid

HRID 55902

반응식

HRID 55902 반응식
[NH2:1][C:2]1[NH:7][C:6]2[NH:8][CH:9]=[C:10]([CH2:11][CH2:12][C:13]3[CH:21]=[CH:20][C:16](C(O)=O)=[CH:15][CH:14]=3)[C:5]=2[C:4](=[O:22])[N:3]=1.CN1CCOCC1.ClC1N=[C:35]([O:37]C)[N:34]=C(OC)N=1.[CH:41]1[CH:46]=[CH:45][C:44]([CH2:47][O:48][C:49]([CH2:51][CH2:52][C@H:53](N)[C:54]([OH:56])=[O:55])=[O:50])=[CH:43][CH:42]=1>CN(C=O)C.O.C(Cl)Cl>[NH2:1][C:2]1[NH:3][C:4](=[O:22])[C:5]2[C:10]([CH2:11][CH2:12][C:13]3[CH:14]=[CH:15][C:16]([C:35]([NH:34][C@H:51]([C:49]([O:48][CH2:47][C:44]4[CH:45]=[CH:46][CH:41]=[CH:42][CH:43]=4)=[O:50])[CH2:52][CH2:53][C:54]([OH:56])=[O:55])=[O:37])=[CH:20][CH:21]=3)=[CH:9][NH:8][C:6]=2[N:7]=1

참가 물질

8

반응물 4

HCID 79724-MethylmorpholineHCID 184502-Chloro-4,6-dimethoxy-1,3,5-triazineHCID 122337L-Glutamic acid, 5-(phenylmethyl) esterHCID 178508847HCID 178508847, 화합물

생성물 1

HCID 135544186(S)-4-(4-(2-(2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl)benzamido)-5-(benzyloxy)-5-oxopentanoic acid

시약·촉매·용매 3

HCID 962Water용매HCID 6228Dimethylformamide용매HCID 6344Dichloromethane용매

반응 조건

온도
25 °C

실험 절차

To a solution of 4-[2-(2-amino-4,7-dihydro-4-oxo-1H-pyrrolo[2,3-d]-pyrimidin-5-yl)ethyl]benzoic acid (38.4 mg, 0.129 mmol) in 5 mL of DMF was added N-methylmorpholine (40.4 mg, 0.399 mmol), followed by the addition of 2-chloro-4,6-dimethoxy-1,3,5-triazine (22.64 mg, 0.129 mmol). The resulting mixture was stirred for 1.5 hours at 25° C., at which time HPLC showed that the reaction was complete. L-glutamic acid γ-benzyl ester (30.6 mg, 0.129 mmol) was added, and stirring was continued at 25° C. until complete conversion of precursor was determined by HPLC (around two hours). To the reaction mixture was added 10 mL of methylene chloride and 10 ml of deionized water, and the mixture was stirred for 15 minutes. The layers were separated. The aqueous layer was extracted with DCM (10 ml×2). The organic phases were combined. The solution was concentrated on rotary-evaporator under reduced pressure. The resulting residue was subjected to flash chromatography on a Biotage system. Yield: 55 mg, 82%. 1HNMR in d6-DMSO, δ ppm: 10.61 (1H, s), 10.20 (1H, s), 8.72 (1H, d, J=10 Hz), 7.78 (2H, d, J=5 Hz), 7.35 (5H, m), 7.30 (2H, m), 6.30 (1H, s), 6.07 (2H, s), 5.14 (2H, s), 3.86 (1H, m), 2.97 (2H, t), 2.84 (2H, t), 2.20 (2H, s), 2.02 (1H, m), 1.95 (1H, m). ESI-MS: 518 [M+H]+.

후처리

  1. stirringstirring
  2. customwas continued at 25° C. until complete conversion of precursor
  3. customwas determined by HPLC (around two hours)
  4. stirringthe mixture was stirred for 15 minutes
  5. customThe layers were separated
  6. extractionThe aqueous layer was extracted with DCM (10 ml×2)
  7. concentrationThe solution was concentrated on rotary-evaporator under reduced pressure

출처 및 근거

ORD 기록
ord-d1ec5b01d08449ee9879680854a6a02f
출처 데이터셋
uspto-grants-2016_09
특허 번호
US09433684B2

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