Hydrochloric Acid → 5-[({7-[3-(7-{[(3-Carboxy-4-hydroxyphenyl)amino]sulfonyl}(2-naphthyl))-2-oxoimidazolidinyl]-(2-naphthyl)}sulfonyl)amino]-2-hydroxybenzoic acid

HRID 1791075Notes

Reaction equation

HRID 1791075 reaction equation
[C:1]([C:4]1[CH:5]=[C:6]([NH:11][S:12]([C:15]2[CH:24]=[C:23]3[C:18]([CH:19]=[CH:20][C:21]([NH:25][CH2:26][CH2:27][NH:28][C:29]4[CH:38]=[C:37]5[C:32]([CH:33]=[CH:34][C:35]([S:39]([NH:42][C:43]6[CH:44]=[CH:45][C:46]([OH:52])=[C:47]([CH:51]=6)[C:48]([OH:50])=[O:49])(=[O:41])=[O:40])=[CH:36]5)=[CH:31][CH:30]=4)=[CH:22]3)=[CH:17][CH:16]=2)(=[O:14])=[O:13])[CH:7]=[CH:8][C:9]=1[OH:10])([OH:3])=[O:2].Cl[C:54](Cl)([O:56]C(=O)OC(Cl)(Cl)Cl)Cl.Cl>C(=O)([O-])[O-].[Na+].[Na+].O.C1COCC1.CS(C)=O.O.C(#N)C>[C:1]([C:4]1[CH:5]=[C:6]([NH:11][S:12]([C:15]2[CH:24]=[C:23]3[C:18]([CH:19]=[CH:20][C:21]([N:25]4[CH2:26][CH2:27][N:28]([C:29]5[CH:38]=[C:37]6[C:32]([CH:33]=[CH:34][C:35]([S:39]([NH:42][C:43]7[CH:44]=[CH:45][C:46]([OH:52])=[C:47]([CH:51]=7)[C:48]([OH:50])=[O:49])(=[O:41])=[O:40])=[CH:36]6)=[CH:31][CH:30]=5)[C:54]4=[O:56])=[CH:22]3)=[CH:17][CH:16]=2)(=[O:13])=[O:14])[CH:7]=[CH:8][C:9]=1[OH:10])([OH:3])=[O:2]

Participants

8

Reactant 3

HCID 313Hydrochloric AcidHCID 94429Triphosgene2×HCID 184210795-({[7-({2-[(7-{[(3-Carboxy-4-hydroxyphenyl)amino]sulfonyl}(2-naphthyl)) amino]-ethyl}-amino)(2-naphthyl)]sulfonyl}amino)-2-hydroxybenzoic acid

Product 1

HCID 233907445-[({7-[3-(7-{[(3-Carboxy-4-hydroxyphenyl)amino]sulfonyl}(2-naphthyl))-2-oxoimidazolidinyl]-(2-naphthyl)}sulfonyl)amino]-2-hydroxybenzoic acid

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 10340Sodium CarbonateSolventHCID 86584666DMSO MeCN waterSolvent

Procedure

To 8 mg (0.011 mmol) of compound 121 in 2 mL of saturated sodium carbonate and 2 mL of water was added 3 mg (0.010 mmol) of triphosgene dissolved in 0.5 mL of THF, dropwise. The addition was made over a period of 15 min. The reaction was judged incomplete by HPLC, so another 4.5 mg (0.015 mmol) of triphosgene in 0.5 mL of THF was added as before. After 2 hours, the reaction was acidified with 6N HCl and a precipitate formed. The suspension was frozen and lyophilized. The resulting solid was dissolved in dimethyl sulfoxide/water/acetonitrile and purified by reverse-phase HPLC (C18, 250×20 mm column) using trifluoroacetic acid (TFA) buffer system (Buffer A: 5% acetonitrile, 95% water, 0.05% TFA; Buffer B: 95% acetonitrile, 5% water, 0.05% TFA; 19 mL/min; 0–100% B in 20 min). This provided 1 mg of the desired compound 122.

Workup

  1. additionThe addition
  2. waitAfter 2 hours
  3. customa precipitate formed
  4. temperatureThe suspension was frozen
  5. custompurified by reverse-phase HPLC (C18, 250×20 mm column)
  6. wait0–100% B in 20 min)

Sources & evidence

ORD record
ord-85a8945eb96d4f8b9bad61099a78bf93
Source dataset
uspto-grants-2006_07
Patent number
US07071231B2

Reaction notes

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