Tetrabutylammonium Fluoride → US10202371, Example 3

HRID 929958Notes

Reaction equation

HRID 929958 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[C:5]([C:12]2[CH:17]=[C:16]([N:18]3[C@@H:22]([CH2:23][O:24][Si](C(C)(C)C)(C4C=CC=CC=4)C4C=CC=CC=4)[C@H:21]([C:42]4[CH:47]=[CH:46][C:45]([O:48][CH3:49])=[CH:44][CH:43]=4)[O:20][C:19]3=[O:50])[N:15]=[C:14]([N:51]3[CH2:56][CH2:55][O:54][CH2:53][CH2:52]3)[N:13]=2)=[CH:4][N:3]=1.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[NH2:1][C:2]1[N:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[C:5]([C:12]2[CH:17]=[C:16]([N:18]3[C@@H:22]([CH2:23][OH:24])[C@H:21]([C:42]4[CH:43]=[CH:44][C:45]([O:48][CH3:49])=[CH:46][CH:47]=4)[O:20][C:19]3=[O:50])[N:15]=[C:14]([N:51]3[CH2:52][CH2:53][O:54][CH2:55][CH2:56]3)[N:13]=2)=[CH:4][N:3]=1

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 86718540(4S,5S)-3-(2'-Amino-2-morpholino-4'-(trifluoromethyl)-[4,5'-bipyrimidin]-6-yl)-4-(((tert-butyldiphenylsilyl)oxy)methyl)-5-(4-methoxyphenyl)oxazolidin-2-one

Product 1

HCID 86718541US10202371, Example 3Yield 50.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of (4S,5S)-3-(2′-amino-2-morpholino-4′-(trifluoromethyl)-[4,5′-bipyrimidin]-6-yl)-4-(((tert-butyldiphenylsilyl)oxy)methyl)-5-(4-methoxyphenyl)oxazolidin-2-one (68 mg, 65 μmol) in THF (2 mL) was added dopwise at 0° C. 1M TBAF in THF (0.05 ml, 0.05 mmol), and the resulting mixture was stirred for 30 min at 0° C. and 1 h at RT. The reaction mixture was concentrated, and the residue was purified by column chromatography using a ratio of hexane/CH2Cl2/MeOH from 100:100:5 to 0:100:5, followed by preparative HPLC (Waters Sun Fire C18, 30×100 mm, 5 um; 0.1% TFA-water/acetonitrile; gradient acetonitrile 30-50% in 20 min) to afford the title compound as white solid (18 mg, 50%); TLC (CH2Cl2/MeOH 19:1) Rf=0.40; tR=0.998 min (UPLC 1); LC-MS: [M+H] 548; Rt 0.96 min; (LCMS method 2). 1H NMR (600 MHz, DMSO-d6): 8.60 (s, 1H), 7.64 (br s, 2H), 7.53 (s, 1H), 7.34 (d, 2H), 7.00 (d, 2H), 5.58 (d, 1H), 5.32 (t, 1H), 4.59 (m, 1H), 4.00 (m, 1H), 3.82 (m, 1H), 3.76 (s, 3H), 3.75-3.55 (m, 81-1).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. customthe residue was purified by column chromatography
  3. customfollowed by preparative HPLC (Waters Sun Fire C18, 30×100 mm, 5 um; 0.1% TFA-water/acetonitrile; gradient acetonitrile 30-50% in 20 min)

Sources & evidence

ORD record
ord-24f79a0934444340aa377d3ff3ad25d5
Source dataset
uspto-grants-2016_03
Patent number
US09296733B2

Reaction notes

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