Diisopropylethylamine → Methyl 2-[4-((2S)-2-[(benzyloxy)carbonyl]amino-3-[6-(1,1-dioxido-3-oxoisothiazolidin-5-yl)biphenyl-3-yl]propanoylamino)butoxy]-6-hydroxybenzoate

HRID 724692Notes

Reaction equation

HRID 724692 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C@@H:12]([CH2:16][C:17]1[CH:18]=[C:19]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[C:20]([CH:23]2[S:27](=[O:29])(=[O:28])[NH:26][C:25](=[O:30])[CH2:24]2)=[CH:21][CH:22]=1)[C:13](O)=[O:14])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=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.[NH2:64][CH2:65][CH2:66][CH2:67][CH2:68][O:69][C:70]1[CH:79]=[CH:78][CH:77]=[C:76]([OH:80])[C:71]=1[C:72]([O:74][CH3:75])=[O:73].C(N(CC)C(C)C)(C)C>CN(C)C=O.C(#N)C>[CH2:1]([O:8][C:9]([NH:11][C@@H:12]([CH2:16][C:17]1[CH:18]=[C:19]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[C:20]([CH:23]2[S:27](=[O:29])(=[O:28])[NH:26][C:25](=[O:30])[CH2:24]2)=[CH:21][CH:22]=1)[C:13]([NH:64][CH2:65][CH2:66][CH2:67][CH2:68][O:69][C:70]1[CH:79]=[CH:78][CH:77]=[C:76]([OH:80])[C:71]=1[C:72]([O:74][CH3:75])=[O:73])=[O:14])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 11832643Methyl 2-(4-aminobutoxy)-6-hydroxybenzoateHCID 58746671(2S)-2-[(benzyloxy)carbonyl]amino-3-[6-(1,1-dioxido-3-oxoisothiazolidin-5-yl)biphenyl-3-yl]propanoic Acid

Product 1

HCID 58746511Methyl 2-[4-((2S)-2-[(benzyloxy)carbonyl]amino-3-[6-(1,1-dioxido-3-oxoisothiazolidin-5-yl)biphenyl-3-yl]propanoylamino)butoxy]-6-hydroxybenzoateYield 48%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolvent

Procedure

To a solution of (2S)-2-[(benzyloxy)carbonyl]amino-3-[6-(1,1-dioxido-3-oxoisothiazolidin-5-yl)biphenyl-3-yl]propanoic acid (18.0 mg, 0.0354 mmol) in N,N-dimethylformamide (1.00 mL) was added benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (16.4 mg, 0.0372 mmol) at 0° C. The reaction was stirred for 15 min and then methyl 2-(4-aminobutoxy)-6-hydroxybenzoate (9.32 mg, 0.0389 mmol) and N,N-diisopropylethylamine (18.5 μL, 0.106 mmol) was added. The resulting solution was stirred for 3 h and then diluted with acetonitrile and purified by preparative LCMS to afford a white solid (12.4 mg, 48%). 1H NMR (400 MHz, CD3OD): δ 8.07 (m, 1H), 7.56 (m, 1H), 7.29 (m, 13H), 6.46 (m, 2H), 5.05 (m, 3H), 4.35 (m, 1H), 3.94 (m, 2H), 3.84 (s, 3H), 3.19 (m, 5H), 2.96 (m, 1H), 1.60 (m, 4H). LCMS found for C38H40N3O10S (M+H)+: m/z=730.

Workup

  1. stirringThe resulting solution was stirred for 3 h
  2. custompurified by preparative LCMS

Sources & evidence

ORD record
ord-9af3062ac95a4da1a65c6bf96b803837
Source dataset
uspto-grants-2006_11
Patent number
US07141596B2

Reaction notes

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