Lithium hydroxide, monohydrate → HCID 178476857, compound

HRID 1948117Notes

Reaction equation

HRID 1948117 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 178472347HCID 178472347, compound

Product 1

HCID 178476857HCID 178476857, compoundYield 38%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of ethyl cis-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 305, 61.7 mg, 0.083 mmol) in THF (0.11 mL) and MeOH (0.11 mL) was charged with a solution of lithium hydroxide, monohydrate (17.4 mg, 0.41 mmol) in H2O (0.11 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 22.3 mg (38%) of the desired product. 1H NMR (400 MHz, MeOD) δ ppm 1.24-1.30 (m, 6H) 1.76-1.89 (m, 6H) 2.11-2.15 (m, 3H) 2.34 (d, J=4.80 Hz, 2H) 2.73 (br. s., 1H) 2.99 (s, 1H) 3.29 (br. s., 1H) 3.34 (s, 1H) 3.89-3.94 (m, 3H) 4.02-4.13 (m, 4H) 6.87 (dt, J=8.21, 2.34 Hz, 1H) 7.03 (t, J=2.02 Hz, 1H) 7.41 (d, J=8.59 Hz, 1H) 7.84 (d, J=0.76 Hz, 1H) 8.03 (d, J=8.34 Hz, 1H) 8.33 (s, 1H) 8.49 (d, J=6.32 Hz, 1H). MS (ES+): m/z 718.15/719.19 (100/98) [MH+]. HPLC: tR=1.47 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-79cba84f2bac42d897abeac5f46bdcae
Source dataset
uspto-grants-2013_03
Patent number
US08399433B2

Reaction notes

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