Diisopropylethylamine → HCID 68410190, compound

HRID 1509788Notes

Reaction equation

HRID 1509788 reaction equation
[C:1]([O:5][C:6](=[O:39])[C@@H:7]([NH:13][C:14]([NH:16][C@@H:17]([CH2:25][CH2:26][CH2:27][CH2:28][NH:29][C:30](=[O:38])[C:31]1[CH:36]=[CH:35][CH:34]=[C:33]([I:37])[CH:32]=1)[C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])=[O:15])[CH2:8][CH2:9][C:10]([OH:12])=O)([CH3:4])([CH3:3])[CH3:2].NCC[C:43]1[CH:48]=[CH:47][C:46]([S:49]([NH2:52])(=[O:51])=[O:50])=[CH:45][CH:44]=1.C[N:54](C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[C:1]([O:5][C:6](=[O:39])[C@@H:7]([NH:13][C:14](=[O:15])[NH:16][C@@H:17]([CH2:25][CH2:26][CH2:27][CH2:28][NH:29][C:30](=[O:38])[C:31]1[CH:36]=[CH:35][CH:34]=[C:33]([I:37])[CH:32]=1)[C:18]([O:20][C:21]([CH3:22])([CH3:24])[CH3:23])=[O:19])[CH2:8][CH2:9][C:10](=[O:12])[NH:54][C:43]1[CH:48]=[CH:47][C:46]([S:49](=[O:51])(=[O:50])[NH2:52])=[CH:45][CH:44]=1)([CH3:3])([CH3:4])[CH3:2]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 1696824-(2-Aminoethyl)benzenesulfonamideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67420293HCID 67420293, compound

Product 1

HCID 68410190HCID 68410190, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of (S)-5-tert-butoxy-4-(3-((S)-1-tert-butoxy-6-(3-iodobenzamido)-1-oxohexan-2-yl)ureido)-5-oxopentanoic acid (212 mg, 0.32 mmol), 4-(2-aminoethyl)benzenesulfonamide (80 mg, 0.40 mmol), HATU (152 mg, 0.40 mmol), and DIPEA (0.50 mL) in DMF (5 mL) was stirred at 50° C. overnight. The solvents were evaporated under reduced pressure to give a residue, which was purified utilizing a Biotage SP4 with a gradient of 10-100% EtOAc in hexane to give (S)-tert-butyl 2-(3-((S)-1-tert-butoxy-1,5-dioxo-5-(4-sulfamoylphenylamino)pentan-2-yl)ureido)-6-(3-iodobenzamido)hexanoate. A solution of the above product was dissolved in TFA (2.0 mL)/DCM (2.0 mL) and stirred at room temperature for 3 h. The solvents were removed under reduced pressure to give a residue, which was purified by Amberchrom™ to give ((S)-2-(3-((S)-1-carboxy-4-oxo-4-(4-sulfamoylphenethylamino)butyl)ureido)-6-(3-iodobenzamido)hexanoic acid (40 mg, 17% over 2 steps) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ 8.54 (t, J=5.4 Hz, 1H), 8.17 (s, 1H), 7.97 (t, J=5.4 Hz, 1H), 7.86 (d, J=8.0 Hz, 1H), 7.83 (d, J=8.0 Hz, 1H), 7.72 (d, J=8.4 Hz, 2H), 7.37 (d, J=8.0 Hz, 2H), 7.28-7.23 (m, 3H), 6.32 (t, J=7.0 Hz, 2H), 4.07-3.99 (m, 2 H), 3.27-2.80 (m, 2H), 2.75 (t, J=7.2 Hz, 2H), 2.10-1.29 (m, 10H); ESMS m/z: 732.2 (M+H)+. Synthesis of Exemplary Formula IV Compounds

Workup

  1. customThe solvents were evaporated under reduced pressure
  2. customto give a residue, which
  3. customwas purified

Sources & evidence

ORD record
ord-112de822884e40b997d0e5cc8dc97606
Source dataset
uspto-grants-2012_07
Patent number
US08211402B2

Reaction notes

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