Diisopropylethylamine → Di-tert-butyl N-[4-[N-(2-amino-3-cyanopyrazin-5-yl) methylamino]-benzoyl]-L-glutamate

HRID 1032023Notes

Reaction equation

HRID 1032023 reaction equation
[NH2:1][C:2]1[C:7]([C:8]#[N:9])=[N:6][C:5]([CH2:10]Cl)=[CH:4][N:3]=1.[NH2:12][C:13]1[CH:38]=[CH:37][C:16]([C:17]([NH:19][C@H:20]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:21][CH2:22][C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])=[O:18])=[CH:15][CH:14]=1.CCN(C(C)C)C(C)C.[K+].[Br-]>CN(C=O)C>[NH2:1][C:2]1[C:7]([C:8]#[N:9])=[N:6][C:5]([CH2:10][NH:12][C:13]2[CH:38]=[CH:37][C:16]([C:17]([NH:19][C@H:20]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:21][CH2:22][C:23]([O:25][C:26]([CH3:29])([CH3:27])[CH3:28])=[O:24])=[O:18])=[CH:15][CH:14]=2)=[CH:4][N:3]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 253877Potassium BromideHCID 5837723-Amino-6-(chloromethyl)pyrazinecarbonitrileHCID 10691066L-Glutamic acid, N-(4-aminobenzoyl)-, bis(1,1-dimethylethyl) ester

Product 1

HCID 15616232Di-tert-butyl N-[4-[N-(2-amino-3-cyanopyrazin-5-yl) methylamino]-benzoyl]-L-glutamate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2-Amino-5-chloromethylpyrazine-3-carbonitrile (1.68 g, 0.01 mol) was added in small portions over 10 min to a stirred solution of di-tert-butyl N-(4-aminobenzoyl)-L-glutamate (3.78 g, 0.01 mol) and i-Pr2NEt (1.74 mL, 1.29 g, 0.01 mol) in dry DMF (25 mL). After 20 hours at room temperature, the solvent was evaporated under reduced pressure and the residue was partitioned between CH2Cl2 and H2O. The organic layer was evaporated and the product purified by column chromatography on a column of neutral Al2O3 (120 g, 3×24 cm) with 50:1 CHCl3 --MeOH as the eluent. Fractions containing the above-specified glutamate (Rf 0.4, silica gel, 9:1 CHCl3 --MeOH) were allowed to evaporate passively in the hood until yellow crystals were formed; yield 3.60 g (59%); mp 71°-78° C; IR (KBr) 3400, 3210, 2990, 2940, 2230 (C≡N), 1730 (ester (C=O), 1635, 1615, 1575, 1515, 1495sh, 1460, 1420, 1395, 1375, 1335, 1315, 1285, 1260 cm-1 ; NMR (CDCl3) δ 1.41 (s, γ-t-OBu), 1.48 (s, α-t-OBu), 2.0-2.4 (m, CH2CH2), 4.37 (m, 2H, CH2NH), 5.35 (m, α-CH and NH), 6.61 (d, J=9 Hz, 3'- and 5'H), 7.67 (d, 9 Hz, 2'- and 4'-H), 8.22 (s, 6--H). Anal. (C26H34N6O5 -0.8 CHCl3) Calcd: C, 53.11; H, 5.79; N, 13.87. Found: C, 53.23; H, 5.94; N, 13.76.

Workup

  1. customthe solvent was evaporated under reduced pressure
  2. customthe residue was partitioned between CH2Cl2 and H2O
  3. customThe organic layer was evaporated
  4. customthe product purified by column chromatography on a column of neutral Al2O3 (120 g, 3×24 cm) with 50:1 CHCl3
  5. additionFractions containing the above-specified glutamate (Rf 0.4, silica gel, 9:1 CHCl3 --MeOH)
  6. customto evaporate passively in the hood until yellow crystals
  7. customwere formed

Sources & evidence

ORD record
ord-cf962f5a694442f49a76726c0bb84984
Source dataset
uspto-grants-1990_09
Patent number
US04956461

Reaction notes

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