2,6-Di-tert-butylpyridine → Tert-butyl [1-benzyl-2-({2-chloro-6-[(methylsulfonyl)(propyl)amino]pyridin-4-yl}methoxy)-1-methylethyl]carbamate

HRID 899448Notes

Reaction equation

HRID 899448 reaction equation
[CH2:1]([C:8]([NH:12][C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16])([CH3:11])[CH2:9][OH:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br[CH2:21][C:22]1[CH:27]=[C:26]([Cl:28])[N:25]=[C:24]([N:29]([CH2:34][CH2:35][CH3:36])[S:30]([CH3:33])(=[O:32])=[O:31])[CH:23]=1.C(C1C=CC=C(C(C)(C)C)N=1)(C)(C)C>ClCCl.[O-]S(C(F)(F)F)(=O)=O.[Ag+]>[CH2:1]([C:8]([NH:12][C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16])([CH3:11])[CH2:9][O:10][CH2:21][C:22]1[CH:23]=[C:24]([N:29]([S:30]([CH3:33])(=[O:32])=[O:31])[CH2:34][CH2:35][CH3:36])[N:25]=[C:26]([Cl:28])[CH:27]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 685102,6-Di-tert-butylpyridine2×HCID 59650918N-[4-(bromomethyl)-6-chloropyridin-2-yl]-N-propylmethanesulfonamideHCID 59694437tert-butyl N-(2-benzyl-1-hydroxypropan-2-yl)carbamate2×

Product 1

HCID 58856338Tert-butyl [1-benzyl-2-({2-chloro-6-[(methylsulfonyl)(propyl)amino]pyridin-4-yl}methoxy)-1-methylethyl]carbamate

Reagents, catalysts & solvents 2

HCID 76223Silver(I) trifluoromethanesulfonateCatalyst2×HCID 6344DichloromethaneSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of tert-butyl (1-benzyl-2-hydroxy-1-methylethyl)carbamate (250 mg, 0.94 mmol, intermediate IV) and N-[4-(bromomethyl)-6-chloropyridin-2-yl]-N-propylmethanesulfonamide (290 mg, 0.85 mmol) in dichloromethane (20 mL) was added silver triflate (290 mg, 1.13 mmol) and 2,6-ditertbutylpyridine polymer bound (1.84 g, 2.83 mmol, Aldrich 37, 782-1). The reaction mixture was stirred at 50° C. in an oil bath for 16 h and then irradiated under microwave (Smith Synthesizer) at 90° C. for 45, 60 and 90 min intervals (3 runs, with addition of additional silver triflate and 2,6-ditertbutylpyridine polymer bound before 2nd and 3rd run). The reaction mixture was filtered on celite, rinsed with dichloromethane, concentrated in vacuo and purified by flash chromatography (silica, 0-30% EtOAc/hexanes) to provide tert-butyl [1-benzyl-2-({2-chloro-6-[(methylsulfonyl)(propyl)amino]pyridin-4-yl}methoxy)-1-methylethyl]carbamate. 1H NMR (400 MHz, CDCl3) δ 7.34-7.16 (m, 7H), 4.56 (s, 2H), 4.50 (s, 1H), 3.83 (t, J=6.8 Hz, 2H), 3.66 (A of AB, d, J=9.2 Hz, 1H), 3.54 (B of AB, d, J=9.2 Hz, 1H), 3.15 (A of AB, d, J=13.2 Hz, 1H), 3.03 (s, 3H), 2.90 (B of AB, d, J=13.2 Hz, 1H), 1.64-1.50 (m, 2H), 1.47 (s, 9H), 1.26 (s, 3H), 0.92 (t, J=7.2 Hz, 3H).

Workup

  1. filtrationThe reaction mixture was filtered on celite
  2. washrinsed with dichloromethane
  3. concentrationconcentrated in vacuo
  4. custompurified by flash chromatography (silica, 0-30% EtOAc/hexanes)

Sources & evidence

ORD record
ord-0c0a6221b1474f27aa4390c502719ba5
Source dataset
uspto-grants-2008_04
Patent number
US07354942B2

Reaction notes

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