Water → HCID 69663549, compound

HRID 1830853Notes

Reaction equation

HRID 1830853 reaction equation
[C:1]1(=[O:7])[O:6][C:4](=O)[CH2:3][CH2:2]1.[NH2:8][CH2:9][C:10]1[N:15]=[C:14]2[S:16][C:17]3[CH2:22][S@@:21](=[O:23])[CH2:20][CH2:19][C:18]=3[C:13]2=[C:12]([C:24]2[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][CH:25]=2)[C:11]=1[Cl:32].C(N1C=CN=C1)(N1C=CN=C1)=O.O>CN(C=O)C>[Cl:32][C:11]1[C:12]([C:24]2[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][CH:25]=2)=[C:13]2[C:18]3[CH2:19][CH2:20][S@:21](=[O:23])[CH2:22][C:17]=3[S:16][C:14]2=[N:15][C:10]=1[CH2:9][N:8]1[C:1](=[O:7])[CH2:2][CH2:3][C:4]1=[O:6]

Participants

6

Reactant 4

HCID 962WaterHCID 7922Succinic anhydrideHCID 682631,1'-CarbonyldiimidazoleHCID 69662788HCID 69662788, compound

Product 1

HCID 69663549HCID 69663549, compoundYield 72.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of succinic anhydride (303.25 g) in DMF (3.5.L) was added (S)-2-(aminomethyl)-3-chloro-4-(4-methoxyphenyl)-7-oxido-5,8-dihydro-6H-thiopyrano-[4′,3′:4,5]thieno[2,3-b]pyridine (1134 g) and the mixture was stirred for 1 hour. To the mixture was slowly added carbonyldiimidazole (935.5 g), and stirred at room temperature for 22 hours and further at 36 to 38° C. for 5 hours. The reaction mixture was added dropwise to water (20 L). After stirring for 2.5 hours, crystals deposited were filtered off and washed with water (1277 g, 86.4%). This product was dissolved in a mixture of acetonitrile (8.7 L) and water (2.9 L) and treated with active carbon. Water (45 L) was added and crystals were filtered off. The crystals were suspended in acetone (2.9 L), stirred at 48 to 52° C. for 1 hour and cooled to room temperature. Crystals were filtered off to obtain the titled compound (997 g). Melting point 217–218.5° C. (decomp.) [α]D20−123.63 (c=0.00490, CHCl3).

Workup

  1. stirringstirred at room temperature for 22 hours and further at 36 to 38° C. for 5 hours
  2. stirringAfter stirring for 2.5 hours
  3. filtrationcrystals deposited were filtered off
  4. washwashed with water (1277 g, 86.4%)
  5. dissolutionThis product was dissolved in a mixture of acetonitrile (8.7 L) and water (2.9 L)
  6. additiontreated with active carbon
  7. additionWater (45 L) was added
  8. filtrationcrystals were filtered off
  9. stirringstirred at 48 to 52° C. for 1 hour
  10. filtrationCrystals were filtered off

Sources & evidence

ORD record
ord-8fd54130e7e24ac4b696537524575808
Source dataset
uspto-grants-2006_06
Patent number
US07067527B2

Reaction notes

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