Tetrahydrofuran → HCID 11563265, compound

HRID 2261913Notes

Reaction equation

HRID 2261913 reaction equation
[C:1]([C:4]1[N:5]=[N:6][N:7]([C:9]2[CH:10]=[C:11]([CH:24]=[C:25]([N:27]([S:31]([CH3:34])(=[O:33])=[O:32])[CH2:28][CH2:29][CH3:30])[CH:26]=2)[C:12]([NH:14][C@@H:15]([C:17]2[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=2)[CH3:16])=[O:13])[CH:8]=1)(=[O:3])[CH3:2].C([Li])[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1.[CH2:43]1COCC1>CCOCC>[F:23][C:20]1[CH:19]=[CH:18][C:17]([C@H:15]([NH:14][C:12](=[O:13])[C:11]2[CH:24]=[C:25]([N:27]([S:31]([CH3:34])(=[O:32])=[O:33])[CH2:28][CH2:29][CH3:30])[CH:26]=[C:9]([N:7]3[CH:8]=[C:4]([C:1]([OH:3])([CH3:43])[CH2:2][C:36]4[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=4)[N:5]=[N:6]3)[CH:10]=2)[CH3:16])=[CH:22][CH:21]=1

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 58990126HCID 58990126, compoundHCID 178506850HCID 178506850, compound2×

Product 1

HCID 11563265HCID 11563265, compound

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

To a solution of 0.013 g (0.027 mmol) 3-(4-acetyl-1H-1,2,3-triazol-1-yl)-N-[(1R)-1-(4-fluorophenyl)ethyl]-5-[(methylsulfonyl)(propyl)amino]benzamide in 1 mL THF at 0° C. was added 0.3 mL (approx. 0.06 mmol) benzyllithium in ether. After 30 min, another 0.3 mL benzyllithium was added and after a further 30 min the reaction mixture was quenched with 10 mL saturated NH4Cl, extracted w. 20 mL EtOAc, washed with 10 mL brine, dried over MgSO4, filtered, and concentrated. Purification by preparative HPLC (5->95% CH3CN/H2O over 30 min, 0.1% added TFA, C18 PRO YMC 20×150 nm) afforded 2 mg N-[(1R)-1-(4-fluorophenyl)ethyl]-3-[4-(1-hydroxy-1-methyl-2-phenylethyl)-1H-1,2,3-triazol-1-yl]-5-[(methylsulfonyl)(propyl)amino]benzamide as a white solid. NMR 1H NMR (CDCl3) δ 8.06 (s, 1H), 7.82 (m, 3H), 7.39 (m, 2H) 7.30 (m, 1H), 7.24 (m, 2H), 7.06 (m, 4H), 6.59 (br d, J=7.14 Hz, 1H), 5.30 (m, 1H), 3.71 (t, J=7.14 Hz, 2H), 3.34 (br d, J=13 Hz, 1H), 3.15 (m, 1H), 2.93 (s, 3H), 1.65 (m, 6H), 1.52 (m, 2H), 0.92 (t, J=7.33 Hz, 3H). High resolution mass spec (FT/ICR) calc M+H=580.2389 found 580.2400.

Workup

  1. customwas quenched with 10 mL saturated NH4Cl
  2. extractionextracted w
  3. wash20 mL EtOAc, washed with 10 mL brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification by preparative HPLC (5->95% CH3CN/H2O over 30 min
  8. addition0.1% added TFA

Sources & evidence

ORD record
ord-a836566ed9ac408788af650a8c825db2
Source dataset
uspto-grants-2010_12
Patent number
US07847100B2

Reaction notes

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