Oxalic Acid → HCID 86753237, compound

HRID 399916Notes

Reaction equation

HRID 399916 reaction equation
[C:1]([OH:6])(=[O:5])[C:2]([OH:4])=[O:3].[CH3:7][C:8]1[O:32][C:11]2=[C:12]3[O:17][CH:16]([CH2:18][NH:19][CH2:20][CH2:21][CH2:22][NH:23][C:24]4[N:29]=[CH:28][CH:27]=[CH:26][N:25]=4)[CH2:15][CH2:14][C:13]3=[CH:30][CH:31]=[C:10]2[C:9]=1[CH3:33].C(O)(=O)C(O)=O>>[C:1]([OH:6])(=[O:5])[C:2]([OH:4])=[O:3].[N:25]1[CH:26]=[CH:27][CH:28]=[N:29][C:24]=1[NH:23][CH2:22][CH2:21][CH2:20][NH:19][CH2:18][CH:16]1[CH2:15][CH2:14][C:13]2=[CH:30][CH:31]=[C:10]3[CH:9]([CH3:33])[CH:8]([CH3:7])[O:32][C:11]3=[C:12]2[O:17]1

Participants

3

Reactant 2

HCID 971Oxalic AcidHCID 131720891HCID 131720891, compound

Product 1

HCID 86753237HCID 86753237, compoundYield 3.3%

Procedure

Intermediate 16-a (0.072 mol) was dissolved in methylbenzene (250 ml)/H (100 ml). The solution was cooled to -70° C. Diisobutylaluminium hydride, 1.5M solution in hexane (0.1 mol) was added dropwise and the mixture was stirred for 1 hour at -70° C. Methanol (15 ml) was added dropwise and the reaction mixture was allowed to warm to room temperature. The mixture was poured out into water, acidified with hydrochloric acid and extracted with diethyl ether. The separated organic layer was dried, filtered and the solvent evaporated. The residue was dissolved in methanol (150 ml). N-2-pyrimidinyl-1,3-propanediamine (0.06 mol) was added and the mixture was hydrogenated with palladium-on-charcoal (small amount) as a catalyst in the presence of thiophene, 4% solution (10 ml). After uptake of H2 (1 equiv), the catalyst was filtered off and the filtrate was evaporated. The residue was purified by column chromatography over silica gel (eluent: CH2Cl2 /CH3OH 90/10). Three fraction groups were collected and the solvent was evaporated, yielding residues (1), (2) and (3) (12 g). A sample of residue (3) (3.6 g) was dissolved in 2-propanone and converted into the ethanedioic acid salt (1:2) with a solution of ethanedioic acid.H2O (0.020 mol) in 2-propanone. The precipitate was filtered off and dried, yielding 4.5 g (46.1%) of (±)-N-[(7,8-dihydro-2,3-dimethyl-6H-furo[3,2-h][1]benzopyran-8-yl)methyl]-N'-2-pyrimidinyl-1,3-propanediamine ethanedioate(1:2); mp. 208.8° C. (comp. 7-a). Residue (2) was repurified by column chromatography over silica gel (eluent: CH2Cl2 /CH3OH 85/15). The desired fractions were collected and the solvent was evaporated. The residue (1.8 g) was dissolved in ethanol and converted into the ethanedioic acid salt (1:2) with ethanedioic acid (0.010 mol). The precipitate was filtered off and dried, yielding 1.1 g (3.3%) (±)-N-2-pyrimidinyl-N'-[(3,6,7,8-tetrahydro-2,3-dimethyl-2H-furo[3,2-h][1]benzopyran-8-yl)methyl]-1,3-propanediamine ethanedioate (1:2); mp. 171.2° C. (comp. 8-a).

Workup

  1. customResidue (2) was repurified by column chromatography over silica gel (eluent: CH2Cl2 /CH3OH 85/15)
  2. customThe desired fractions were collected
  3. customthe solvent was evaporated
  4. dissolutionThe residue (1.8 g) was dissolved in ethanol
  5. filtrationThe precipitate was filtered off
  6. customdried

Sources & evidence

ORD record
ord-31c595ccd58a4a59a4ec51cdc8dc3700
Source dataset
uspto-grants-1998_10
Patent number
US05824682

Reaction notes

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