Methylamine → 4-Amino-1-[3,5-bis-O-(4-chlorobenzoyl)-2-deoxy-beta-D-erythro-pentofuranosyl]-1,3,5-triazin-2(1H)-one

HRID 2043792Notes

Reaction equation

HRID 2043792 reaction equation
C(OC1O[C@H](COC(=O)C2C=CC(Cl)=CC=2)[C@@H](OC(=O)C2C=CC(Cl)=CC=2)C1)(=O)C.C[Si](NC1N=C(O[Si](C)(C)C)N=CN=1)(C)C.[Si](OS(C(F)(F)F)(=O)=O)(C)(C)C.CN.[NH2:61][C:62]1[N:67]=[CH:66][N:65]([C@H:68]2[O:82][C@H:81]([CH2:83][O:84][C:85](=[O:93])[C:86]3[CH:91]=[CH:90][C:89]([Cl:92])=[CH:88][CH:87]=3)[C@@H:70]([O:71][C:72](=[O:80])[C:73]3[CH:78]=[CH:77][C:76]([Cl:79])=[CH:75][CH:74]=3)[CH2:69]2)[C:64](=[O:94])[N:63]=1>CO.ClCCl>[NH2:61][C:62]1[N:67]=[CH:66][N:65]([C@@H:68]2[O:82][C@H:81]([CH2:83][O:84][C:85](=[O:93])[C:86]3[CH:91]=[CH:90][C:89]([Cl:92])=[CH:88][CH:87]=3)[C@@H:70]([O:71][C:72](=[O:80])[C:73]3[CH:78]=[CH:77][C:76]([Cl:79])=[CH:75][CH:74]=3)[CH2:69]2)[C:64](=[O:94])[N:63]=1

Participants

8

Reactant 5

HCID 6329MethylamineHCID 65367Trimethylsilyl triflateHCID 529002N-(Trimethylsilyl)-4-((trimethylsilyl)oxy)-1,3,5-triazin-2-amineHCID 532591611-O-Acetyl-3,5-bis(4-chlorobenzoyl)-2-deoxy-D-riboseHCID 675340374-Amino-1-(3,5-bis-O-(4-chlorobenzoyl)-2-deoxy-alpha-D-erythro-pentofuranosyl)-1,3,5-triazin-2(1H)-one

Product 1

HCID 452568534-Amino-1-[3,5-bis-O-(4-chlorobenzoyl)-2-deoxy-beta-D-erythro-pentofuranosyl]-1,3,5-triazin-2(1H)-oneYield 40%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

1-O-Acetyl-3,5-di-O-(4-chloro-benzoyl)-2-deoxy-D-ribofuranose (3.603 Kg, 7.68 mol), 2-[(trimethylsilyl)amino]-4-[(trimethylsilyl)oxy]-s-triazine (1.970 Kg, 7.68 mol) and dichloromethane (71.6 Kg) were charged to a suitable reactor. The mixture was cooled to 0° C. TMSOTf (1.791 Kg, 8.06 mol) was added to the solution at 0° C. and stirred for 5 hours. 2M methyl amine in methanol solution (about 3.95 Kg) was then added to the mixture at 0° C. and stirred for 45 mins. The mixture was diluted with dichloromethane (71.6 Kg) and washed with saturated sodium bicarbonate solution (39.8 Kg) at 25° C. The organic layer was dried using molecule sieves (36 Kg). The molecule sieves were filtered and rinsed with dichloromethane (60.1 Kg). The organic layer was evaporated to dryness at 35° C. The solid was milled and vacuum dried at 45° C. to obtain 2.99 Kg (5.92 mol) of 4-amino-1-[3,5-di-O-(4-chloro-benzoyl)-2-deoxy-β-D-ribofuranosyl]-1H-[1,3,5]triazin-2-one (compound Ib) in 52% HPLC purity (40% yield based on 1-O-acetyl-3,5-di-O-(4-chloro-benzoyl)-2-deoxy-D-ribofuranose) and 4-amino-1-[3,5-di-O-(4-chloro-benzoyl)-2-deoxy-α-D-ribofuranosyl]-1H-[1,3,5]triazin-2-one (compound IVa) mixture in 27% HPLC purity. That α-anomer to β-anomer ratio was 1.0:1.91.

Workup

  1. stirringstirred for 45 mins
  2. washwashed with saturated sodium bicarbonate solution (39.8 Kg) at 25° C
  3. customThe organic layer was dried
  4. filtrationThe molecule sieves were filtered
  5. washrinsed with dichloromethane (60.1 Kg)
  6. customThe organic layer was evaporated to dryness at 35° C
  7. customThe solid was milled
  8. customvacuum dried at 45° C.

Sources & evidence

ORD record
ord-3dc3398bfa824444acc202beeafd8d69
Source dataset
uspto-grants-2013_11
Patent number
US08586729B2

Reaction notes

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