Citric Acid → HCID 19808383, compound

HRID 373859Notes

Reaction equation

HRID 373859 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]2[S:14][CH2:13][C:12]3[C:11]([C:15](=[O:28])[CH:16]([C:26]#[N:27])[C:17]([NH:19][C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)=[O:18])=[N:10][N:9]([C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=4)[C:8]=3[C:6]=2[CH:7]=1.[CH2:35]([N:37]([CH2:40][CH3:41])[CH2:38]C)[CH3:36].C(O)(=O)CC(CC(O)=O)(C(O)=O)[OH:45]>O1CCCC1>[C:26]([CH:16]([C:15]([C:11]1[C:12]2[CH2:13][S:14][C:5]3[CH:4]=[CH:3][C:2]([N:1]=[CH:38][N:37]4[CH2:40][CH2:41][O:45][CH2:36][CH2:35]4)=[CH:7][C:6]=3[C:8]=2[N:9]([C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=2)[N:10]=1)=[O:28])[C:17]([NH:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)=[O:18])#[N:27]

Participants

5

Reactant 3

HCID 311Citric AcidHCID 8471TriethylamineHCID 18962912HCID 18962912, compound

Product 1

HCID 19808383HCID 19808383, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-15 °C

Procedure

N-Formylmorpholine (7.58 g) dissolved in anhydrous ethyl ether (200 ml) is reacted with oxalyl chloride (8.02 g) under stirring at room temperature for 20 hours. The precipitate is filtered, washed with anhydrous ethyl ether and dried in vacuo at room temperature for 1 hour to yield 8.9 g of 4-chloromethylene-morpholinium chloride. This compound (5.47 g) is added portionwise at -15°60 C. to a stirred solution of 3-(8-amino-1,4-dihydro-1-phenyl-[1]-benzothiopyrano[4,3-c]pyrazol-3-yl)-2-cyano-3-oxo-N-phenyl-propanamide (3 g) in anhydrous tetrahydrofuran (130 ml) containing triethylamine (8.96 ml). The reaction mixture is kept under stirring at -15° C. for 2 hours and then at about 0° C. for 2 hours again. Finally it is diluted with ice water and acidified to pH 4 with citric acid. The precipitate is filtered, fired in vacuo at 50° C. and then purified over a SiO2 column using chloroform/methanol30% NH4OH 85/12/0.5 as eluent. The recovered product is crystallized from methanol to yield 1.4 g of 2-cyano-3(1,4-dihydro-8-morpholinomethyleneamino-1-phenyl-[1]-benzothiopyrano[4,3-c]pyrazol-3-yl)-3-oxo-N-phenyl-propanamide, m.p. 205°-210° C.

Workup

  1. waitat about 0° C. for 2 hours again
  2. filtrationThe precipitate is filtered
  3. customfired in vacuo at 50° C.
  4. custompurified over a SiO2 column
  5. customThe recovered product is crystallized from methanol

Sources & evidence

ORD record
ord-44f2a0cb7f1e48ee9a67e6c52cf5d9bf
Source dataset
uspto-grants-1992_11
Patent number
US05166152

Reaction notes

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