Lithium hydroxide, monohydrate → HCID 178476858, compound

HRID 1948118Notes

Reaction equation

HRID 1948118 reaction equation
[CH2:1]([O:3][P:4]([CH2:9][C:10]1[CH:15]=[CH:14][C:13]([NH:16][C:17]2[N:22]=[C:21]([NH:23][C:24]3[CH:33]=[CH:32][C:31]([C@H:34]4[CH2:39][CH2:38][C@H:37]([C:40]([O:42]CC)=[O:41])[CH2:36][CH2:35]4)=[C:30]4[C:25]=3[C:26](=[O:46])[C:27]([CH3:45])=[CH:28][NH:29]4)[C:20]([C:47]([F:50])([F:49])[F:48])=[CH:19][N:18]=2)=[C:12]([O:51][CH3:52])[CH:11]=1)([O:6][CH2:7][CH3:8])=[O:5])[CH3:2].O.[OH-].[Li+]>C1COCC1.CO.O>[CH2:7]([O:6][P:4]([CH2:9][C:10]1[CH:15]=[CH:14][C:13]([NH:16][C:17]2[N:22]=[C:21]([NH:23][C:24]3[CH:33]=[CH:32][C:31]([C@H:34]4[CH2:35][CH2:36][C@H:37]([C:40]([OH:42])=[O:41])[CH2:38][CH2:39]4)=[C:30]4[C:25]=3[C:26](=[O:46])[C:27]([CH3:45])=[CH:28][NH:29]4)[C:20]([C:47]([F:48])([F:50])[F:49])=[CH:19][N:18]=2)=[C:12]([O:51][CH3:52])[CH:11]=1)([O:3][CH2:1][CH3:2])=[O:5])[CH3:8]

Participants

6

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 178472348HCID 178472348, compound

Product 1

HCID 178476858HCID 178476858, compoundYield 64.6%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of Ethyl trans-4-(5-{[2-({4-[(diethoxyphosphoryl)methyl]-2-methoxyphenyl}amino)-5-(trifluoromethyl)pyrimidin-4-yl]amino}-3-methyl-4-oxo-1,4-dihydroquinolin-8-yl)cyclohexanecarboxylate (Example 304, 72.0 mg, 0.097 mmol) in THF (0.125 mL) and MeOH (0.129 mL) was charged with a solution of lithium hydroxide, monohydrate (20.2 mg, 0.48 mmol) in H2O (0.129 mL) and allowed to stir at rt for 30 hrs. The reaction was concentrated under reduced pressure. The material was purified on an Isco combi-flash unit using DCM/MeOH (100:0→95:5) as eluent to afford 45 mg (60%) of the desired product. 1H NMR (400 MHz, MeOD) δ ppm 1.24-1.33 (m, 6H) 1.66-1.86 (m, 4H) 1.96-2.04 (m, 2H) 2.12-2.14 (m, 3H) 2.15-2.22 (m, 2H) 3.39-3.43 (m, 1H) 3.46-3.50 (m, 1H) 3.91-3.94 (m, 3H) 4.05-4.11 (m, 4H) 6.88-6.94 (m, 1H) 7.03-7.07 (m, 1H) 7.47-7.52 (m, 1H) 7.83-7.86 (m, 1H) 8.01-8.06 (m, 1H) 8.33-8.35 (m, 1H) 8.50-8.59 (m, 1H). MS (ES+): m/z 718.22/719.26 (100/98) [MH+]. HPLC: tR=1.43 min (Micromass TOF: polar—3 min).

Workup

  1. concentrationThe reaction was concentrated under reduced pressure
  2. customThe material was purified on an Isco combi-flash unit

Sources & evidence

ORD record
ord-fcb805357a434cfa8b7a55ea38bcab00
Source dataset
uspto-grants-2013_03
Patent number
US08399433B2

Reaction notes

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