Diisopropylethylamine → Methyl 2-[4-((2S)-3-[3-bromo-4-(1,1-dioxido-3-oxoisothiazolidin-5-yl)phenyl]-2-[(phenylsulfonyl)-amino]propanoylamino)butoxy]-6-hydroxybenzoate

HRID 724665Notes

Reaction equation

HRID 724665 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([CH2:16][C@H:17]([NH:21][S:22]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)(=[O:24])=[O:23])[C:18](O)=[O:19])[CH:5]=[CH:6][C:7]=1[CH:8]1[S:12](=[O:14])(=[O:13])[NH:11][C:10](=[O:15])[CH2:9]1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.Cl.[NH2:68][CH2:69][CH2:70][CH2:71][CH2:72][O:73][C:74]1[CH:83]=[CH:82][CH:81]=[C:80]([OH:84])[C:75]=1[C:76]([O:78][CH3:79])=[O:77]>CN(C=O)C>[Br:1][C:2]1[CH:3]=[C:4]([CH2:16][C@H:17]([NH:21][S:22]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)(=[O:24])=[O:23])[C:18]([NH:68][CH2:69][CH2:70][CH2:71][CH2:72][O:73][C:74]2[CH:83]=[CH:82][CH:81]=[C:80]([OH:84])[C:75]=2[C:76]([O:78][CH3:79])=[O:77])=[O:19])[CH:5]=[CH:6][C:7]=1[CH:8]1[S:12](=[O:14])(=[O:13])[NH:11][C:10](=[O:15])[CH2:9]1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 69597617Methyl 2-(4-aminobutoxy)-6-hydroxybenzoate hydrochlorideHCID 69597760(2S)-3-[3-Bromo-4-(1,1-dioxido-3-oxoisothiazolidin-5-yl)phenyl]-2-[(phenylsulfonyl)-amino]propanoic acid

Product 1

HCID 69597679Methyl 2-[4-((2S)-3-[3-bromo-4-(1,1-dioxido-3-oxoisothiazolidin-5-yl)phenyl]-2-[(phenylsulfonyl)-amino]propanoylamino)butoxy]-6-hydroxybenzoateYield 62.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

(2S)-3-[3-bromo-4-(1,1-dioxido-3-oxoisothiazolidin-5-yl)phenyl]-2-[(phenylsulfonyl)-amino]-propanoic acid (10.3 mg, 0.020 mmol) in DMF (1 mL) was treated with benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (10.6 mg, 0.024 mmol). After stirring 5 minutes at rt a solution of N,N-diisopropylethylamine (17.4 L, 0.10 mmol) and methyl 2-(4-aminobutoxy)-6-hydroxybenzoate hydrochloride (8.27 mg, 0.030 mmol) in DMF (1 mL) was added. The solution stirred at rt for 2 h. Purification by preparative LCMS afforded product as a white solid (9.2 mg, 62%). 1H NMR (400 MHz, CD3OD): δ 7.96 (brs, 1H), 7.69–7.65 (m, 2H), 7.52–7.14 (m, 7H), 6.51–6.46 (m, 2H), 5.62–5.59 (m, 1H), 4.00–3.94 (m, 13H), 3.87 (s, 3H), 3.44–3.38 (m, 1H), 3.36–3.30 (m. 1H), 3.06–3.00 (m, 1H), 2.98–2.91 (m, 2H), 2.81–2.72 (m, 1H), 1.64–1.60 (m, 2H), 1.51–1.47 (m, 2H); LCMS found for C30H33BrN3O10S2 (M+H)+: m/z=738.

Workup

  1. additionwas added
  2. customPurification by preparative LCMS

Sources & evidence

ORD record
ord-e6064df250554990b458c37fda9767a7
Source dataset
uspto-grants-2006_11
Patent number
US07141596B2

Reaction notes

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