4-Methylmorpholine → N-[4-[2-(2-amino-4,5,6,7-tetrahydro-4-oxo 3H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-L-glutamic acid diethyl ester

HRID 1656796Notes

Reaction equation

HRID 1656796 reaction equation
ClC1C(OC)=NN=NC=1OC.[NH2:12][C:13]1[NH:14][C:15](=[O:33])[C:16]2[CH:21]([CH2:22][CH2:23][C:24]3[CH:32]=[CH:31][C:27]([C:28](O)=[O:29])=[CH:26][CH:25]=3)[CH2:20][NH:19][C:17]=2[N:18]=1.CN1CCOCC1.Cl.[CH2:42]([O:44][C:45](=[O:55])[C@H:46]([CH2:48][CH2:49][C:50]([O:52][CH2:53][CH3:54])=[O:51])[NH2:47])[CH3:43]>CN(C)C=O>[CH2:42]([O:44][C:45](=[O:55])[C@H:46]([CH2:48][CH2:49][C:50]([O:52][CH2:53][CH3:54])=[O:51])[NH:47][C:28](=[O:29])[C:27]1[CH:31]=[CH:32][C:24]([CH2:23][CH2:22][CH:21]2[C:16]3[C:15](=[O:33])[NH:14][C:13]([NH2:12])=[N:18][C:17]=3[NH:19][CH2:20]2)=[CH:25][CH:26]=1)[CH3:43]

Participants

6

Reactant 4

HCID 79724-Methylmorpholine3×HCID 73960Glutamic acid diethyl ester hydrochlorideHCID 12493616Chloro-dimethoxy-triazine2×HCID 1355127464-(2-[2-amino-4,5,6,7-tetrahydro-4-oxo-3H-pyrrolo[2,3-d]pyrimidin-5-yl]ethyl)benzoic acid

Product 1

HCID 136062642N-[4-[2-(2-amino-4,5,6,7-tetrahydro-4-oxo 3H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-L-glutamic acid diethyl esterYield 52%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

1.12 Grams (6.36 mmol) of chlorodimethoxytriazine was added to a solution of 1.91 grams (6.36 mmol) of 4-(2-[2-amino-4,5,6,7-tetrahydro-4-oxo-3H-pyrrolo[2,3-d]pyrimidin-5-yl]ethyl)benzoic acid and 0.63 grams (6.3 mmol) of N-methylmorpholine (NMM) in 20 ml of dimethylformamide (DMF) at room temperature. The resulting mixture was stirred at room temperature for 2 hours. Next, an additional 0.3 grams (2.97 mmol) of NMM and 0.22 grams (1.25 mmol) of chlorodimethoxytriazine was added.to the solution and the mixture stirred for an additional 30 min. Then, 0.64 grams (6.3 mmol) of NMM and 1.52 grams (6.3 mmol) of diethyl-L-glutamate hydrochloride was added to the mixture. After stirring overnight at room temperature, the resulting suspension was mixed with 30 grams of silica gel and dried under vacuum. The residue was added to a column of 70 grams silica gel and eluted with 500 ml of CH2Cl2 -EtOH 90:10 followed by CH2Cl2 -EtOH 80:20. 1.62 Grams (52%) of purified N-[4-[2-(2-amino-4,5,6,7-tetrahydro-4-oxo-3H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-L-glutamic acid diethyl ester was obtained as a colorless powder. Selected data: 1H NMR (DMSO-d6) δ 9.55 (s, 1H), 8.60 (d, J=7.4 Hz, 1 H), 7.73 (d, J=8.3 Hz, 2H) 7.27 (d, J=8.3 Hz, 2H), 6.28 (s, 1H), 6.20 (s, 2H), 4.38 (m, 1H), 4.05 (q, J=7.1 Hz, 2H), 3.99 (q, J=7.1 Hz, 2H), 3.40 (m, 1H), 3.02 (m, 2H), 2.65 (t, J=7.6 Hz, 2H), 2.39 (t, J=7.5 Hz, 2H), 2.00 (m, 3H), 1.54 (m, 1H), 1.13 (t, J=7.1 Hz, 3H), 1.11 (t, J=7.1 Hz, 3H).

Workup

  1. stirringthe mixture stirred for an additional 30 min
  2. stirringAfter stirring overnight at room temperature
  3. additionthe resulting suspension was mixed with 30 grams of silica gel
  4. customdried under vacuum
  5. additionThe residue was added to a column of 70 grams silica gel
  6. washeluted with 500 ml of CH2Cl2 -EtOH 90:10

Sources & evidence

ORD record
ord-5849d46b239042229d27ba9b5414d166
Source dataset
uspto-grants-1993_10
Patent number
US05254716

Reaction notes

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