Water → 4-[5-[[3-methyl-2-[3-[5-[N-[(2-methylpropan-2-yl)oxycarbonyl]carbamimidoyl]-2-methylsulfanylthiophen-3-yl]sulfonylphenyl]-5-(2-trimethylsilylethoxycarbonylamino)phenyl]carbamoylamino]pentoxy]benzoic acid

HRID 723224Notes

Reaction equation

HRID 723224 reaction equation
[OH-].[Li+].C[O:4][C:5](=[O:65])[C:6]1[CH:11]=[CH:10][C:9]([O:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][NH:18][C:19]([NH:21][C:22]2[CH:27]=[C:26]([NH:28][C:29]([O:31][CH2:32][CH2:33][Si:34]([CH3:37])([CH3:36])[CH3:35])=[O:30])[CH:25]=[C:24]([CH3:38])[C:23]=2[C:39]2[CH:44]=[CH:43][CH:42]=[C:41]([S:45]([C:48]3[CH:52]=[C:51]([C:53]([NH:55][C:56]([O:58][C:59]([CH3:62])([CH3:61])[CH3:60])=[O:57])=[NH:54])[S:50][C:49]=3[S:63][CH3:64])(=[O:47])=[O:46])[CH:40]=2)=[O:20])=[CH:8][CH:7]=1.O>O1CCOCC1>[C:59]([O:58][C:56]([NH:55][C:53](=[NH:54])[C:51]1[S:50][C:49]([S:63][CH3:64])=[C:48]([S:45]([C:41]2[CH:40]=[C:39]([C:23]3[C:24]([CH3:38])=[CH:25][C:26]([NH:28][C:29]([O:31][CH2:32][CH2:33][Si:34]([CH3:35])([CH3:36])[CH3:37])=[O:30])=[CH:27][C:22]=3[NH:21][C:19](=[O:20])[NH:18][CH2:17][CH2:16][CH2:15][CH2:14][CH2:13][O:12][C:9]3[CH:10]=[CH:11][C:6]([C:5]([OH:65])=[O:4])=[CH:7][CH:8]=3)[CH:44]=[CH:43][CH:42]=2)(=[O:46])=[O:47])[CH:52]=1)=[O:57])([CH3:62])([CH3:60])[CH3:61]

Participants

5

Reactant 3

HCID 962WaterHCID 3939Lithium HydroxideHCID 145857710HCID 145857710, compound

Product 1

HCID 1458576514-[5-[[3-methyl-2-[3-[5-[N-[(2-methylpropan-2-yl)oxycarbonyl]carbamimidoyl]-2-methylsulfanylthiophen-3-yl]sulfonylphenyl]-5-(2-trimethylsilylethoxycarbonylamino)phenyl]carbamoylamino]pentoxy]benzoic acidYield 100%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

Lithium hydroxide (45.8 mg, 2.08 mmol) was added to a solution of 4-(5-{3-[3′-[5-(tert-butoxycarbonylamino-imino-methyl)-2-methylsulfanyl-thiophene-3-sulfonyl]-6-methyl-4-(2-trimethylsilanyl-ethoxycarbonylamino)-biphenyl-2-yl]-ureido}-pentyloxy)-benzoic acid methyl ester (280 mg, 0.298 mmol, Example 283: step c) in 1,4-dioxane:water (10 mL, 2:1) over 2 days at rt. The solvents were removed in vacuo. The residue was diluted in water, acidified to pH˜5 with acetic acid, and extracted with EtOAc. The organic layer was washed with brine and dried over magnesium sulfate. The solvents were removed in vacuo to afford the title compound as a yellow solid (276 mg, quantitative). 1H-NMR (CDCl3/CD3OD): δ 7.93–7.99 (m, 3H), 7.83–7.86 (m, 2H), 7.52–7.59 (m, 2H), 7.15–7.20 (m, 2H), 6.85–6.89 (m, 2H), 4.21–4.26 (m, 2H), 3.99 (t, 2H, J=6.43 Hz), 3.13–3.24 (m, 2H), 2.61 (s, 3H), 2.02 (s, 3H), 1.75–1.83 (m, 2H), 1.43–1.56 (m, 13H), 1.02–1.08 (m, 2H), 0.07 (s, 9H).

Workup

  1. customThe solvents were removed in vacuo
  2. additionThe residue was diluted in water
  3. extractionextracted with EtOAc
  4. washThe organic layer was washed with brine
  5. dry with materialdried over magnesium sulfate
  6. customThe solvents were removed in vacuo

Sources & evidence

ORD record
ord-26dba131e2784075ba9c39a58892c2c6
Source dataset
uspto-grants-2006_11
Patent number
US07138530B2

Reaction notes

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