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

反応式

HRID 55902 の反応式
[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

参加物

8

反応物 4

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

生成物 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

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒

反応条件

温度
25 °C

実験手順

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]+.

後処理

  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

出典と根拠

ORDレコード
ord-d1ec5b01d08449ee9879680854a6a02f
出典データセット
uspto-grants-2016_09
特許番号
US09433684B2

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