Formaldehyde → HCID 67317184, compound

HRID 1013005Notes

Reaction equation

HRID 1013005 reaction equation
[CH2:1]([N:8]([CH2:10][CH:11]1[C:16]2=[N:17][C:18]([C:23]([NH:25][CH2:26][C:27]3[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=3)=[O:24])=[C:19]([OH:22])[C:20](=[O:21])[N:15]2[CH2:14][CH2:13][N:12]1[C:34](OC(C)(C)C)=O)[CH3:9])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.C=O.C([BH3-])#N.[Na+]>C(Cl)Cl.FC(F)(F)C(O)=O.C(O)(=O)C>[CH2:1]([N:8]([CH2:10][CH:11]1[C:16]2=[N:17][C:18]([C:23]([NH:25][CH2:26][C:27]3[CH:28]=[CH:29][C:30]([F:33])=[CH:31][CH:32]=3)=[O:24])=[C:19]([OH:22])[C:20](=[O:21])[N:15]2[CH2:14][CH2:13][N:12]1[CH3:34])[CH3:9])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 712FormaldehydeHCID 8471TriethylamineHCID 5003444Sodium cyanoborohydrideHCID 67316844HCID 67316844, compound

Product 1

HCID 67317184HCID 67317184, compound

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 21863450Trifluoroacetic acid methylene chlorideSolvent

Procedure

A solution of compound of Step 7 in dry CH2Cl2/trifluoroacetic acid (8/2 v/v) was stirred at room temperature for 1.5 hours, then evaporated under reduced pressure. MS (ES) C24H26FN5O3 requires 451. Found: 452 (M+H+). The residue was taken in methanol and the solution was treated with 3 equivalents of triethylamine and stirred for 10 minutes. The mixture was acidified with some drops of acetic acid (pH=5) then treated with formaldehyde (3 eq.) and sodium cyanoborohydride. After over night stirring at room temperature, volatiles were removed by rotary evaporation and the resulting residue, dissolved in the minimum amount of MeOH, was applied on cation-exchange resin. The resin was washed with MeOH and the product was eluted with 1 M ammonia in methanol. The pooled fractions were concentrated to dryness under reduced pressure to get 9-{[benzyl(methyl)amino]methyl}-N-(4-fluorobenzyl)-3-hydroxy-8-methyl-4-oxo-6,7,8,9-tetrahydro-4H-pyrazino[1,2-a]pyrimidine-2-carboxamide as a brown oil. MS (ES) C25H28FN5O3 requires 465. Found: 466 (M+H+). The crude compound was dissolved in methanol, treated with 2.5 eq. of 1 N HCl and the solution was stirred overnight under a hydrogen atmosphere in the presence of catalytic 10% Pd/C. Catalyst was then filtered off through celite, and the filtrate was evaporated under reduced pressure to afford title compound as hydrochloric salt. MS (ES) C18H22FN5O3 requires 375. Found: 476 (M+H+).

Workup

  1. customevaporated under reduced pressure
  2. stirringAfter over night stirring at room temperature
  3. customvolatiles were removed by rotary evaporation
  4. dissolutionthe resulting residue, dissolved in the minimum amount of MeOH
  5. washThe resin was washed with MeOH
  6. washthe product was eluted with 1 M ammonia in methanol
  7. concentrationThe pooled fractions were concentrated to dryness under reduced pressure

Sources & evidence

ORD record
ord-f7346f50ebdf4f97b9d5a41093b99c6e
Source dataset
uspto-grants-2011_07
Patent number
US07981879B2

Reaction notes

Loading…