Pyridine → (S)-2-[2-(Benzo[1,2,5]thiadiazole-4-sulfonylamino)-4-iodo-benzoylamino]-3-(3,4-dichloro-phenyl)-propionic acid

HRID 1593845Notes

Reaction equation

HRID 1593845 reaction equation
C[O:2][C:3](=[O:37])[C@@H:4]([NH:14][C:15](=[O:36])[C:16]1[CH:21]=[CH:20][C:19]([I:22])=[CH:18][C:17]=1[NH:23][S:24]([C:27]1[C:32]2=[N:33][S:34][N:35]=[C:31]2[CH:30]=[CH:29][CH:28]=1)(=[O:26])=[O:25])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([Cl:12])=[C:8]([Cl:13])[CH:7]=1.COC(=O)[C@@H](NC(=O)C1C=CC(I)=CC=1N)CC1C=CC(Cl)=C(Cl)C=1.ClS(C1C2C(=NSN=2)C=CC=1)(=O)=O.N1C=CC=CC=1.NCCN(CCN)CCN>C(Cl)Cl>[N:35]1[S:34][N:33]=[C:32]2[C:27]([S:24]([NH:23][C:17]3[CH:18]=[C:19]([I:22])[CH:20]=[CH:21][C:16]=3[C:15]([NH:14][C@@H:4]([CH2:5][C:6]3[CH:11]=[CH:10][C:9]([Cl:12])=[C:8]([Cl:13])[CH:7]=3)[C:3]([OH:37])=[O:2])=[O:36])(=[O:25])=[O:26])=[CH:28][CH:29]=[CH:30][C:31]=12

Participants

7

Reactant 5

HCID 1049PyridineHCID 77731Tris(2-aminoethyl)amineHCID 27354592,1,3-Benzothiadiazole, 4-chlorosulfonyl-HCID 58999935(S)-2-[2-(Benzo[1,2,5]thiadiazole-4-sulfonylamino)-4-iodo-benzoylamino]-3-(3,4-dichloro-phenyl)-propionic acid methyl esterHCID 68770882(S)-2-(2-amino-4-iodo-benzoylamino)-3-(3,4-dichloro-phenyl)-propionic acid methyl ester

Product 1

HCID 11693225(S)-2-[2-(Benzo[1,2,5]thiadiazole-4-sulfonylamino)-4-iodo-benzoylamino]-3-(3,4-dichloro-phenyl)-propionic acidYield 99%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(S)-2-[2-(Benzo[1,2,5]thiadiazole-4-sulfonylamino)-4-iodo-benzoylamino]-3-(3,4-dichloro-phenyl)-propionic acid methyl ester. To a solution of (S)-2-(2-amino-4-iodo-benzoylamino)-3-(3,4-dichloro-phenyl)-propionic acid methyl ester (39 mg, 0.079 mmol) in DCM (1 mL) was added 4-chlorosulfonyl-2,1,3-benzothiadiazole (37 mg, 0.158 mmol) and pyridine (30 μL, 0.371 mmol). The mixture was-shaken overnight at rt, then polymer bound tris(2-aminoethyl)amine resin was added. The resulting mixture was shaken for 2 h, and the resin was removed by filtration and rinsed with DCM. TBD methyl polystyrene resin was then added and the mixture was shaken for 2 h. The liquid was drained and the resin was washed with DCM (3×). A solution of 10% TFA in DCM (3 mL) was added to the resin and the mixture was shaken for 1.5 h. The resin was removed by filtration, washed with 10% TFA in DCM and the filtrate was concentrated to provide the desired product as a white solid (55 mg, 99%). 1H NMR (400 MHz, CDCl3): 11.10 (s, 1H), 8.36 (dd, J=7.0, 0.8, 1H), 8.24 (dd, J=8.8, 0.8, 1H), 8.02 (d, J=1.5, 1H), 7.75 (dd, J=8.8, 7.1, 1H), 7.37-7.32 (m, 2H), 7.16 (d, J=2.0, 1H), 6.96 (d, J=8.3, 1H), 6.92 (dd, J=8.2, 2.0, 1H), 6.67 (d, J=7.3, 1H), 4.96 (q, J=5.7, 1H), 3.83 (s, 3H), 3.20-3.12 (m, 2H).

Workup

  1. additionwas added
  2. stirringThe resulting mixture was shaken for 2 h
  3. customthe resin was removed by filtration
  4. washrinsed with DCM
  5. additionTBD methyl polystyrene resin was then added
  6. stirringthe mixture was shaken for 2 h
  7. washthe resin was washed with DCM (3×)
  8. additionA solution of 10% TFA in DCM (3 mL) was added to the resin
  9. stirringthe mixture was shaken for 1.5 h
  10. customThe resin was removed by filtration
  11. washwashed with 10% TFA in DCM
  12. concentrationthe filtrate was concentrated

Sources & evidence

ORD record
ord-5be5acd5b1df44b6b16d88e97ada3871
Source dataset
uspto-grants-2007_11
Patent number
US07297816B2

Reaction notes

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