Tetrahydrofuran → [5-{[2-({4-[(Diethoxyphosphoryl)methyl]-2-methoxyphenyl}amino)-5-(trifluoromethyl)pyrimidin-4-yl]amino}-3-methyl-4-oxoquinolin-1(4H)-yl]acetic acid

HRID 1948107Notes

Reaction equation

HRID 1948107 reaction equation
C([O:3][C:4](=[O:47])[CH2:5][N:6]1[C:15]2[C:10](=[C:11]([NH:16][C:17]3[C:22]([C:23]([F:26])([F:25])[F:24])=[CH:21][N:20]=[C:19]([NH:27][C:28]4[CH:33]=[CH:32][C:31]([CH2:34][P:35]([O:40][CH2:41][CH3:42])([O:37][CH2:38][CH3:39])=[O:36])=[CH:30][C:29]=4[O:43][CH3:44])[N:18]=3)[CH:12]=[CH:13][CH:14]=2)[C:9](=[O:45])[C:8]([CH3:46])=[CH:7]1)C.C1COCC1.O[Li].O>CO>[CH2:41]([O:40][P:35]([CH2:34][C:31]1[CH:32]=[CH:33][C:28]([NH:27][C:19]2[N:18]=[C:17]([NH:16][C:11]3[CH:12]=[CH:13][CH:14]=[C:15]4[C:10]=3[C:9](=[O:45])[C:8]([CH3:46])=[CH:7][N:6]4[CH2:5][C:4]([OH:47])=[O:3])[C:22]([C:23]([F:24])([F:26])[F:25])=[CH:21][N:20]=2)=[C:29]([O:43][CH3:44])[CH:30]=1)([O:37][CH2:38][CH3:39])=[O:36])[CH3:42]

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 168937Lithium hydroxide, monohydrateHCID 58292890ethyl[5-{[2-({4-[(diethoxyphosphoryl)methyl]-2-methoxyphenyl}amino)-5-(trifluoromethyl)pyrimidin-4-yl]amino}-3-methyl-4-oxoquinolin-1(4H)-yl]acetate

Product 1

HCID 58293027[5-{[2-({4-[(Diethoxyphosphoryl)methyl]-2-methoxyphenyl}amino)-5-(trifluoromethyl)pyrimidin-4-yl]amino}-3-methyl-4-oxoquinolin-1(4H)-yl]acetic acidYield 61%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of ethyl[5-{[2-({4-[(diethoxyphosphoryl)methyl]-2-methoxyphenyl}amino)-5-(trifluoromethyl)pyrimidin-4-yl]amino}-3-methyl-4-oxoquinolin-1(4H)-yl]acetate (Example 300, 41 mg, 0.061 mmol) in MeOH (0.5 mL), and THF (0.5 mL) was charged with LiOH H2O (25.6 mg, 0.61 mmol). The resulting mixture was stirred at room temperature for 5 h. The reaction mixture was concentrated under reduced pressure. The material was purified by prep TLC (5% MeOH in DCM) to give 24.1 mg of the desired product (yield: 61%). 1H NMR (DMSO-d6, 400 MHz): δ=1.20 (m, 6H), 1.99 (s, 3H), 3.24 (d, J=21.2 Hz, 2H), 3.78 (s, 3H), 3.99 (m, 2H), 6.90 (d, 1H), 7.03 (s, 1H), 7.43 (s, br, 1H), 7.61 (d, J=7.2 Hz, 1H), 7.94 (s, br, 1H). 8.36 (s, 1H), 8.51-8.56 (m, 2H). MS (ES+): m/z 651.19 [MH+]. HPLC: tR=1.32 min (UPLC TOF, polar—3 min).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. customThe material was purified by prep TLC (5% MeOH in DCM)

Sources & evidence

ORD record
ord-846e16c2a725476fac0275f88be886c6
Source dataset
uspto-grants-2013_03
Patent number
US08399433B2

Reaction notes

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