Sodium Bicarbonate → {4-[2-(4-methoxyphenyl)-pyrimidin-4-yl]-phenyl}-carbamic acid (2S,3R,4R,5S,6S)-3,4,5-trimethoxy-6-methyl-tetrahydropyran-2-yl ester

HRID 1475166Notes

Reaction equation

HRID 1475166 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:14]=[C:13]([C:15]3[CH:20]=[CH:19][C:18]([NH2:21])=[CH:17][CH:16]=3)[CH:12]=[CH:11][N:10]=2)=[CH:5][CH:4]=1.C[Si](C)(C)[N-][Si](C)(C)C.[K+].[CH3:32][O:33][CH:34]1[CH:39]([O:40][CH3:41])[CH:38]([O:42][CH3:43])[CH:37]([CH3:44])[O:36][CH:35]1[O:45][C:46](=O)[O:47]C1C=CC([N+]([O-])=O)=CC=1.C(=O)(O)[O-].[Na+]>C1COCC1.C1(C)C=CC=CC=1>[CH3:32][O:33][C@@H:34]1[C@H:39]([O:40][CH3:41])[C@@H:38]([O:42][CH3:43])[C@H:37]([CH3:44])[O:36][C@H:35]1[O:45][C:46](=[O:47])[NH:21][C:18]1[CH:19]=[CH:20][C:15]([C:13]2[CH:12]=[CH:11][N:10]=[C:9]([C:6]3[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:8][CH:7]=3)[N:14]=2)=[CH:16][CH:17]=1

Participants

7

Reactant 4

HCID 516892Sodium BicarbonateHCID 3251421Potassium bis(trimethylsilyl)amideHCID 67519234Carbonic acid 4-nitrophenyl ester 3,4,5-trimethoxy-6-methyl-tetrahydropyran-2-yl esterHCID 675194204-[2-(4-Methoxyphenyl)-pyrimidin-4-yl]-phenylamine

Product 1

HCID 44230218{4-[2-(4-methoxyphenyl)-pyrimidin-4-yl]-phenyl}-carbamic acid (2S,3R,4R,5S,6S)-3,4,5-trimethoxy-6-methyl-tetrahydropyran-2-yl esterYield 8.1%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a mixture cooled in an ice bath of 112 mg (0.404 mmol) of 4-[2-(4-methoxyphenyl)-pyrimidin-4-yl]-phenylamine in 1.5 mL of dry THF was added dropwise via syringe 0.81 mL (0.40 mmol) of a 0.5 M solution of potassium hexamethyldisilazide in toluene over a 10-15 minute period. This solution was then added dropwise via syringe to a solution cooled in an ice bath of 126 mg (0.386 mmol) of carbonic acid 4-nitrophenyl ester 3,4,5-trimethoxy-6-methyl-tetrahydropyran-2-yl ester in 2 mL of THF. The contents were allowed to gradually warm to room temperature and stir overnight and were added to cold saturated sodium bicarbonate. The mixture was extracted two times with ethyl ether and the combined extracts were dried (MgSO4). Concentration gave a red oil which was purified by chromatography on silica gel using 1:1 hexanes/EtOAc to afford 16 mg (8%) of Compound 234. 1H NMR (300 MHz, CDCl3) δ 8.79 (d, J=5.2 Hz, 1H), 8.55 (d, J=8.8 Hz, 2H), 8.25 (d, J=8.8 Hz, 2H), 7.62 (d, J=8.5 Hz, 2H), 7.53 (d, J=5.5 Hz, 1H), 7.05 (d, J=9.0 Hz, 2H), 6.84 (br s, 1H), 6.26 (d, J=1.7 Hz, 1H), 3.92 (s, 3H), 3.71-3.69 (m, 2H), 3.61 (s, 3H), 3.60 (s, 3H), 3.57 (s, 3H), 3.55-3.47 (m, 1H), 3.24 (t, J=9.4 Hz, 1H), 1.36 (d, J=6.1 Hz, 3H); MS (API-ES+) 510 ([M+H]+, 100).

Workup

  1. additionThis solution was then added dropwise via syringe to a solution
  2. extractionThe mixture was extracted two times with ethyl ether
  3. dry with materialthe combined extracts were dried (MgSO4)
  4. concentrationConcentration
  5. customgave a red oil which
  6. customwas purified by chromatography on silica gel using 1:1 hexanes/EtOAc

Sources & evidence

ORD record
ord-a36c482830704e298fbc63cb3f1a03fb
Source dataset
uspto-grants-2015_04
Patent number
US09018363B2

Reaction notes

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