Diisopropylethylamine → ethyl 6-[[3-methyl-4-[3-[5-[N-[(2-methylpropan-2-yl)oxycarbonyl]carbamimidoyl]-2-methylsulfanylthiophen-3-yl]sulfonylphenyl]phenyl]carbamoylamino]hexanoate

HRID 723265Notes

Reaction equation

HRID 723265 reaction equation
C(N(C(C)C)CC)(C)C.[CH2:10]([O:12][C:13](=[O:22])[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][N:19]=[C:20]=[O:21])[CH3:11].[C:23]([O:27][C:28](=[O:56])[NH:29][C:30]([C:32]1[S:33][C:34]([S:54][CH3:55])=[C:35]([S:37]([C:40]2[CH:41]=[C:42]([C:46]3[CH:51]=[CH:50][C:49]([NH2:52])=[CH:48][C:47]=3[CH3:53])[CH:43]=[CH:44][CH:45]=2)(=[O:39])=[O:38])[CH:36]=1)=[NH:31])([CH3:26])([CH3:25])[CH3:24]>C(Cl)Cl>[CH2:10]([O:12][C:13](=[O:22])[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][NH:19][C:20]([NH:52][C:49]1[CH:50]=[CH:51][C:46]([C:42]2[CH:43]=[CH:44][CH:45]=[C:40]([S:37]([C:35]3[CH:36]=[C:32]([C:30]([NH:29][C:28]([O:27][C:23]([CH3:24])([CH3:25])[CH3:26])=[O:56])=[NH:31])[S:33][C:34]=3[S:54][CH3:55])(=[O:39])=[O:38])[CH:41]=2)=[C:47]([CH3:53])[CH:48]=1)=[O:21])[CH3:11]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 3445675Ethyl 6-isocyanatohexanoateHCID 145857675tert-butyl N-[4-[3-(4-amino-2-methylphenyl)phenyl]sulfonyl-5-methylsulfanylthiophene-2-carboximidoyl]carbamate

Product 1

HCID 145857680ethyl 6-[[3-methyl-4-[3-[5-[N-[(2-methylpropan-2-yl)oxycarbonyl]carbamimidoyl]-2-methylsulfanylthiophen-3-yl]sulfonylphenyl]phenyl]carbamoylamino]hexanoateYield 43%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Diisopropylethylamine (35 μL, 0.2 mmol), 6-isocyanato-hexanoic acid ethyl ester (40 μL, 0.2 mmol), and {[4-(4′-amino-2′-methyl-biphenyl-3-sulfonyl)-5-methylsulfanyl-thiophen-2-yl]-imino-methyl}-carbamic acid tert-butyl ester ((Example 220: step b) 20 mg, 0.04 mmol) were stirred for 24 h in DCM (1 mL). The solution was partitioned between EtOAc (40 mL) and 0.1 N HCl (10 mL) and was washed with additional 0.1N HCl (2×10 mL), NaHCO3 (10 mL), and brine (20 mL). The solution was dried, concentrated in vacuo, and purified by SiO2 preparative TLC to yield the product (12 mg, 43%). 1H-NMR (CDCl3): δ 8.06 (s, 1H), 7.94 (m, 1H), 7.81 (m, 1H), 7.46 (m, 2H), 7.23 (br t, 1H, J=5.4 Hz), 7.15 (m, 1H), 7.07 (m, 2H), 6.97 (m, 1H), 5.32 (br t, 1H), 4.15 (q, 2H, J=7.2 Hz), 2.40 (s, 3H), 2.30 (t, 2H, J=7.3 Hz), 2.11 (s, 3H), 1.54–1–70 (m, 4H), 1.51 (s, 9H) 1.35 (m, 2H), 1.25 (t, 3H, J=7.3 Hz).

Workup

  1. customThe solution was partitioned between EtOAc (40 mL) and 0.1 N HCl (10 mL)
  2. washwas washed with additional 0.1N HCl (2×10 mL), NaHCO3 (10 mL), and brine (20 mL)
  3. customThe solution was dried
  4. concentrationconcentrated in vacuo
  5. custompurified by SiO2 preparative TLC

Sources & evidence

ORD record
ord-d0ce0a1be6af47e7ab64a228bdd05e7b
Source dataset
uspto-grants-2006_11
Patent number
US07138530B2

Reaction notes

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