Lithium Hydroxide → HCID 71062246, compound

HRID 528812Notes

Reaction equation

HRID 528812 reaction equation
[Cl:1][C:2]1[C:3]([C:47](=[O:57])[N:48]([CH2:53][CH2:54][CH2:55][CH3:56])[CH2:49][CH2:50][CH2:51][CH3:52])=[N:4][N:5]([C:8]2[CH:34]=[CH:33][C:11]([C:12]([NH:14][S:15]([C:18]3[CH:27]=[C:26]4[C:21]([CH:22]=[CH:23][C:24]([C:28]([O:30]CC)=[O:29])=[CH:25]4)=[CH:20][CH:19]=3)(=[O:17])=[O:16])=[O:13])=[CH:10][C:9]=2[C:35]([N:37]2[CH2:46][CH2:45][C:44]3[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=3)[CH2:38]2)=[O:36])[C:6]=1[CH3:7].[Li+].[OH-]>CCO.C1COCC1>[Cl:1][C:2]1[C:3]([C:47](=[O:57])[N:48]([CH2:53][CH2:54][CH2:55][CH3:56])[CH2:49][CH2:50][CH2:51][CH3:52])=[N:4][N:5]([C:8]2[CH:34]=[CH:33][C:11]([C:12]([NH:14][S:15]([C:18]3[CH:27]=[C:26]4[C:21]([CH:22]=[CH:23][C:24]([C:28]([OH:30])=[O:29])=[CH:25]4)=[CH:20][CH:19]=3)(=[O:17])=[O:16])=[O:13])=[CH:10][C:9]=2[C:35]([N:37]2[CH2:46][CH2:45][C:44]3[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=3)[CH2:38]2)=[O:36])[C:6]=1[CH3:7]

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 71062261HCID 71062261, compound

Product 1

HCID 71062246HCID 71062246, compoundYield 72.7%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
40 °C

Procedure

To a solution of ethyl 7-(N-(4-(4-chloro-3-(dibutylcarbamoyl)-5-methyl-1H-pyrazol-1-yl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzoyl)sulfamoyl)-2-naphthoate (Example 16, 84 mg, 0.10 mmol) in EtOH (0.5 mL) and THF (0.5 mL) was added 2N LiOH (0.5 mL, 1.03 mmol). The reaction mixture was stirred for 2 h at 40° C., concentrated to remove volatiles, diluted with water and quenched with 1N HCl. The solution was concentrated in vacuo and purified by preparative HPLC to afford the title compound (57 mg, 68%) as a white solid. 1H NMR (DMSO-d6, 2:1 mixture of amide rotamers) δ 8.41 (s, 1H), 8.36 (s, 1H), 8.07 (t, J=7.3 Hz, 2H), 7.99 (d, J=1.3 Hz, 1H), 7.88 (s, 2H), 7.79 (d, J=8.8 Hz, 1H), 7.55-7.51 (m, 1H), 7.20-7.07 (m, 3.5H), 6.97 (d, J=7.5 Hz, 0.5H), 4.10 (br s, 6H), 2.97 (br s, 1.5H), 2.74 (br s, 1.5H), 2.19 (s, 2H), 2.14 (s, 1H), 1.38 (br s, 1H), 1.29-1.12 (m, 6H), 1.01-0.91 (m, 2H), 0.88-0.82 (m, 3H), 0.68-0.61 (m, 3H); MS(ESI+) m/z 784.2 (M+H)+.

Workup

  1. concentrationconcentrated
  2. customto remove volatiles
  3. additiondiluted with water
  4. customquenched with 1N HCl
  5. concentrationThe solution was concentrated in vacuo
  6. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-b9b0faf306db46339f029487d2b8b0e6
Source dataset
uspto-grants-2016_05
Patent number
US09346795B2

Reaction notes

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