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 1527654Notes

Reaction equation

HRID 1527654 reaction equation
[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

Participants

8

Reactant 4

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

Product 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

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
25 °C

Procedure

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]+.

Workup

  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

Sources & evidence

ORD record
ord-991a51474d244ef08fc36aa1645e0d06
Source dataset
uspto-grants-2015_07
Patent number
US09089610B2

Reaction notes

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