4-Methylmorpholine → (S)-2-({5-[3-(2-Amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-6-yl)-propyl]-thiophene-2-carbonyl}-amino)-pentanedioic acid diethyl ester

HRID 889076Notes

Reaction equation

HRID 889076 reaction equation
[NH2:1][C:2]1[NH:3][C:4](=[O:22])[C:5]2[CH:10]=[C:9]([CH2:11][CH2:12][CH2:13][C:14]3[S:18][C:17]([C:19]([OH:21])=O)=[CH:16][CH:15]=3)[NH:8][C:6]=2[N:7]=1.CN1CCOCC1.ClC1N=C(OC)N=C(OC)N=1.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=O)C>[CH2:42]([O:44][C:45](=[O:55])[C@@H:46]([NH:47][C:19]([C:17]1[S:18][C:14]([CH2:13][CH2:12][CH2:11][C:9]2[NH:8][C:6]3[N:7]=[C:2]([NH2:1])[NH:3][C:4](=[O:22])[C:5]=3[CH:10]=2)=[CH:15][CH:16]=1)=[O:21])[CH2:48][CH2:49][C:50]([O:52][CH2:53][CH3:54])=[O:51])[CH3:43]

Participants

6

Reactant 4

HCID 79724-Methylmorpholine2×HCID 184502-Chloro-4,6-dimethoxy-1,3,5-triazineHCID 73960Glutamic acid diethyl ester hydrochlorideHCID 1360441775-[3-(2-Amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-6-yl)-propyl]-thiophene-2-carboxylic acid

Product 1

HCID 136330210(S)-2-({5-[3-(2-Amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-6-yl)-propyl]-thiophene-2-carbonyl}-amino)-pentanedioic acid diethyl esterYield 63%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 9 (254 mg, 0.8 mmol) in anhydrous DMF (10 mL) was added N-methylmorpholine (145 mg, 1.44 mmol) and 2-chloro-4,6-dimethoxy-1,3,5-triazine (253 g, 1.44 mmol). The resulting mixture was stirred at room temperature for 2 h. To this mixture were added N-methylmorpholine (145 mg, 1.44 mmol) and L-glutamate diethyl ester hydrochloride (290 mg, 1.2 mmol). The reaction mixture was stirred for an additional 4 h at room temperature and then evaporated to dryness under reduced pressure. The residue was dissolved in the minimum amount of CHCl3/MeOH (4:1) and chromatographed on a silica gel column (2×15 cm) and with 5% CHCl3 in MeOH as the eluent. Fractions that showed the desired spot (TLC) were pooled and the solvent evaporated to dryness to afford 252 mg of 10 as yellow powder in 63% yield. 1H NMR (DMSO-d6): δ 1.14-1.21 (m, 6H), 1.81-2.05 (m, 4H), 2.32-2.39 (t, J=7.6 Hz, 2H), 2.49-2.52 (t, J=7.2 Hz, 2H), 2.78-2.81 (t, J=7.2 Hz, 2H), 4.02-4.07 (m, 4H), 4.30-4.35 (m, 1H), 5.88 (s, 1H), 5.94 (s, 2H), 6.89-6.90 (d, J=3.6 Hz, 1H), 7.68-7.69 (d, J=3.6 Hz, 1H), 8.61-8.63 (d, J=8 Hz, 1H), 10.71 (s, 1H), 11.19 (s, 1H).

Workup

  1. stirringThe reaction mixture was stirred for an additional 4 h at room temperature
  2. customevaporated to dryness under reduced pressure
  3. dissolutionThe residue was dissolved in the minimum amount of CHCl3/MeOH (4:1)
  4. customchromatographed on a silica gel column (2×15 cm) and with 5% CHCl3 in MeOH as the eluent
  5. customthe solvent evaporated to dryness

Sources & evidence

ORD record
ord-f313ae8895c04eb99ab84fc7a75d2279
Source dataset
uspto-grants-2012_08
Patent number
US08252804B2

Reaction notes

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