Succinic Acid → HCID 178457292, compound

HRID 386685Notes

Reaction equation

HRID 386685 reaction equation
[C:1]([OH:8])(=[O:7])[CH2:2][CH2:3][C:4]([OH:6])=[O:5].[CH2:9]([N:12]([CH2:55][CH2:56][CH3:57])[C:13]([CH2:15][O:16][C:17](=[O:54])[CH2:18][CH2:19][NH:20][S:21]([C:24]1[CH:29]=[CH:28][CH:27]=[C:26]([C:30]([N:32]2[CH2:53][CH2:52][C:35]3([NH:39]/[C:38](=[N:40]/[C:41]([C:43]4[C:48]([NH2:49])=[N:47][C:46]([NH2:50])=[C:45]([Cl:51])[N:44]=4)=[O:42])/[NH:37][CH2:36]3)[CH2:34][CH2:33]2)=[O:31])[CH:25]=1)(=[O:23])=[O:22])=[O:14])[CH2:10][CH3:11]>CC(C)=O>[C:1]([OH:8])(=[O:7])[CH2:2][CH2:3][C:4]([OH:6])=[O:5].[CH2:55]([N:12]([CH2:9][CH2:10][CH3:11])[C:13]([CH2:15][O:16][C:17](=[O:54])[CH2:18][CH2:19][NH:20][S:21]([C:24]1[CH:29]=[CH:28][CH:27]=[C:26]([C:30]([N:32]2[CH2:53][CH2:52][C:35]3([NH:39]/[C:38](=[N:40]/[C:41]([C:43]4[C:48]([NH2:49])=[N:47][C:46]([NH2:50])=[C:45]([Cl:51])[N:44]=4)=[O:42])/[NH:37][CH2:36]3)[CH2:34][CH2:33]2)=[O:31])[CH:25]=1)(=[O:23])=[O:22])=[O:14])[CH2:56][CH3:57]

Participants

4

Reactant 2

HCID 1110Succinic AcidHCID 178457291HCID 178457291, compound2×

Product 1

HCID 178457292HCID 178457292, compound

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent4×

Conditions

Temperature
45 °C

Procedure

The solution of succinic acid (0.50 g, 4.23 mmol) in acetone (20 ml) was heated at 45° C. for 1 h and treated with a portion of the solution of 3-(3-{2-[(E)-3,5-diamino-6-chloro-pyrazine-2-carbonylimino]-1,3,8-triaza-spiro[4.5]decane-8-carbonyl}-benzenesulfonyl amino)-propionic acid dipropylcarbamoylmethyl ester in acetone (1.62 g of solution) over 10 min. The resulting mixture was treated with a suspension of seed crystals of 3-(3-{2-[(E)-3,5-diamino-6-chloro-pyrazine-2-carbonylimino]-1,3,8-triaza-spiro[4.5]decane-8-carbonyl}-benzenesulfonylamino)-propionic acid dipropylcarbamoylmethyl ester (as prepared using method C, 20 mg) in acetone (300 mg) and stirred at 45° C. for 30 min. The remaining solution of 3-(3-{2-[(E)-3,5-diamino-6-chloro-pyrazine-2-carbonylimino]-1,3,8-triaza-spiro[4.5]decane-8-carbonyl}-benzenesulfonylamino)-propionic acid dipropylcarbamoyl methyl ester in acetone (31.38 g) was added to the mixture over 5 h and heating continued at 45° C. for 1 h. The suspension was cooled to 25° C. over 1 h and stirred for a further 1 h. The suspension was filtered over a glass frit and the filter cake was washed with acetone (2×5 g). The filter cake was dried at 50° C. to afford the title compound; HPLC Rt 4.02 min, method ii; 1H NMR (400 MHz, DMSO-d6) δ 7.87 (1H, m), 7.78 (1H, m), 7.69 (1H, m), 7.68 (1H, m), 6.85 (2H, br s), 4.73 (2H, s), 3.84-3.20 (6H and water, br hump), 3.17-3.09 (4H, m), 3.04 (2H, t), 2.53 (2H, under DMSO), 2.39 (4H, s), 1.80 (2H, br s), 1.70 (2H, br s), 1.55-1.37 (4H, m), 0.85 (3H, t), 0.78 (3H, t) (Please note: The two exchangeable succinate protons and 3-4 acidic NH resonances were not observed directly due to the very broad nature of some of the exchangeable resonances; Melting Temperature Tm (DSC)=149° C.

Workup

  1. temperatureheating
  2. waitcontinued at 45° C. for 1 h
  3. temperatureThe suspension was cooled to 25° C. over 1 h
  4. stirringstirred for a further 1 h
  5. filtrationThe suspension was filtered over a glass frit
  6. washthe filter cake was washed with acetone (2×5 g)
  7. customThe filter cake was dried at 50° C.

Sources & evidence

ORD record
ord-06b00c81c0b84308a38e1a46c568bcbb
Source dataset
uspto-grants-2013_02
Patent number
US08372845B2

Reaction notes

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