Benzylamine → Diisopropylethylamine

HRID 1432372Notes

Reaction equation

HRID 1432372 reaction equation
ClC1N=C(F)N=C2C=1NC=N2.C(N)[C:13]1[CH:18]=[CH:17]C=CC=1.N[CH2:21][C:22]1[CH:27]=C[CH:25]=[CH:24][N:23]=1.NCC1C=NC=CC=1.NCC1C=CN=CC=1>CCCCO>[CH3:25][CH2:24][N:23]([CH:18]([CH3:17])[CH3:13])[CH:22]([CH3:27])[CH3:21]

Participants

7

Reactant 5

HCID 7504BenzylamineHCID 195092-PyridinemethanamineHCID 310183-PyridinemethanamineHCID 773174-PyridinemethanamineHCID 52879146-Chloro-2-fluoropurine

Product 1

HCID 81531Diisopropylethylamine

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Procedure

For the synthesis of the 6-benzylamino-, 6-(pyridin-2-ylmethyl), 6-(pyridin-3-ylmethyl) and 6-(pyridin-2-ylmethyl)-intermediates, the initial step involved reaction of 6-chloro-2-fluoro-purine 29 [Gray, N. S.; Kwon, S.; Schultz, P. G. Tetrahedron Lett., 1997, 38 (7), 1161-1164] with either benzylamine, 2-(aminomethyl)pyridine, 3-(aminomethyl)pyridine or 4-(aminomethyl)pyridine, in n-BuOH the presence of DIPEA, to afford the corresponding 6-substituted intermediates 30. These compounds then underwent reaction with 2-bromopropane and K2CO3 in DMA [Havlicek, L.; Hunus, J.; Vesely, J.; Leclerc, S.; Meijer; L.; Shaw, G.; Strnad, M.; J Med Chem., 1997, 40 (4), 408412], to afford their corresponding N9-isopropyl substituted intermediates 31. These purine intermediates were finally reacted with the aminoalcohols (1-2, 15-22, and 27-28) in DMSO/n-BuOH/DIEA at 140° C. over 72 h to give their corresponding C2-substituted aminoalkyl analogues 32.

Sources & evidence

ORD record
ord-09e1f6e74f964d8e85ea94985ac7b919
Source dataset
uspto-grants-2009_11
Patent number
US07612079B2

Reaction notes

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