Acetic Acid → HCID 136207166, compound

HRID 2165718Notes

Reaction equation

HRID 2165718 reaction equation
C([NH:4][C:5]1[NH:6][C:7](=[O:39])[C:8]([CH2:15][CH2:16][CH2:17][NH:18][C:19]2[CH:38]=[CH:37][C:22]([C:23]([NH:25][C@H:26]([C:33]([O:35]C)=[O:34])[CH2:27][CH2:28][C:29]([O:31]C)=[O:30])=[O:24])=[CH:21][CH:20]=2)=[C:9]([NH:11]C(=O)C)[N:10]=1)(=O)C.C=O.[C:42]([BH3-])#N.[Na+].C(O)(=O)C>C(#N)C.CN(C)C=O>[NH2:4][C:5]1[NH:6][C:7](=[O:39])[C:8]([CH2:15][CH2:16][CH2:17][N:18]([C:19]2[CH:20]=[CH:21][C:22]([C:23]([NH:25][C@H:26]([C:33]([OH:35])=[O:34])[CH2:27][CH2:28][C:29]([OH:31])=[O:30])=[O:24])=[CH:37][CH:38]=2)[CH3:42])=[C:9]([NH2:11])[N:10]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 135990644HCID 135990644, compound

Product 1

HCID 136207166HCID 136207166, compoundYield 130.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolvent

Procedure

To a stirred solution of 1.99 g (3.6 mmol) of dimethyl N-[4-[3-(2,4-bis(acetamido)-1,6-dihydro-6-oxo-5-pyrimidinyl)propylamino]benzoyl]-L-glutamate in 50 ml of acetonitrile and 5 ml of dimethylformamide was added 2 ml of 37% aqueous formaldehyde followed by 0.50 g (8.0 mmol) of sodium cyanoborohydride and 2 ml of acetic acid. After 18 hours the mixture was filtered to remove the solids and the filtrate was spin evaporated in vacuo. The residue was diluted with 100 ml of ice water, and then extracted with four 25 ml portions of methylene dichloride. The combined extracts were filtered through glass wool and spin evaporated in vacuo to give 2.1 g of the title compound as an oil which was a single spot on TLC. The oil was dissolved in 50 ml of ethanol and 50 ml of 1N sodium hydroxide and stirred at 70° C. for 20 hours. The reaction was cooled and spin evaporated in vacuo to a syrup. The syrup was dissolved in 50 ml of water, cooled on ice, and acidified to pH 3-4 with concentrated hydrochloric acid. The white solids were collected, washed with water, and finally with ether; yield, 1.10 g (67%), mp 190°-200° C. (one spot on TLC). Recrystallization from ethanol gave the analytical sample; yield, 0.54 g (33%, mp (166°-1678° changes to hard foam) 198°-204°; TLC (pyridine:BuOH:H2O/1:1:1); NMR (DMSO-d6) δ 8.16 (d, 1H, ArCONH), 7.71 (d, 2H, Ar), 6.66 (d, 2H, Ar), 5.94 (s, 2H, NH2), 5.76 (s, 2H, NH2) 4.36 (m, 1H, CHCO2H), 3.34 (m, 2H, CH2N(CH3)Ar), 2.93 (s, 3H, NCH3).

Workup

  1. filtrationAfter 18 hours the mixture was filtered
  2. customto remove the solids
  3. customevaporated in vacuo
  4. additionThe residue was diluted with 100 ml of ice water
  5. extractionextracted with four 25 ml portions of methylene dichloride
  6. filtrationThe combined extracts were filtered through glass wool
  7. customspin evaporated in vacuo

Sources & evidence

ORD record
ord-f6a39e1597484b6b85499bc8df926a8a
Source dataset
uspto-grants-1990_07
Patent number
US04940713

Reaction notes

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