Methanesulfonyl chloride → HCID 59853059, compound

HRID 1670257Notes

Reaction equation

HRID 1670257 reaction equation
[F:1][C:2]1[CH:18]=[C:17]([N+:19]([O-:21])=[O:20])[CH:16]=[CH:15][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][N:8]=[CH:7][C:6]=1[C:11]#[C:12][CH2:13]O.CCN(C(C)C)C(C)C.CS(Cl)(=O)=O.[C:36]([O:40][C:41](=[O:48])[NH:42][CH2:43][CH:44]1[CH2:47][NH:46][CH2:45]1)([CH3:39])([CH3:38])[CH3:37]>C1COCC1.CN(C=O)C>[F:1][C:2]1[CH:18]=[C:17]([N+:19]([O-:21])=[O:20])[CH:16]=[CH:15][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][N:8]=[CH:7][C:6]=1[C:11]#[C:12][CH2:13][N:46]1[CH2:47][CH:44]([CH2:43][NH:42][C:41](=[O:48])[O:40][C:36]([CH3:38])([CH3:37])[CH3:39])[CH2:45]1

Participants

7

Reactant 4

HCID 31297Methanesulfonyl chlorideHCID 81531Diisopropylethylamine2×HCID 15346872tert-butyl N-(azetidin-3-ylmethyl)carbamateHCID 59852955HCID 59852955, compound

Product 1

HCID 59853059HCID 59853059, compoundYield 48.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 3-(4-(2-fluoro-4-nitrophenoxy)pyridin-3-yl)prop-2-yn-1-ol (43 mg, 0.15 mmol) and DIPEA (45 μL, 0.26 mmol) in anhydrous THF (1.5 mL) was cooled to 0° C. and treated with methanesulfonyl chloride (15 mg, 0.11 mmol) in portions. After stirring at 0° C. for 1 h, the mixture was concentrated under reduced pressure. The residue was treated with DMF (1.0 mL), DIPEA (45 μL, 0.26 mmol) and azetidin-3-ylmethyl-carbamic acid tert-butyl ester (Beta Pharma Inc., 145 mg, 0.78 mmol) and stirred at rt for 2 h. The reaction mixture was partitioned between EtOAc and saturated aq. NaHCO3 solution and the EtOAc phase separated, washed with brine dried (MgSO4) and concentrated in vacuo. The residue was purified by flash chromatography on SiO2 eluting with 1-5% MeOH/CH2Cl2 to afford the title compound (33 mg, 48%) as a colorless oil. 1H NMR (DMSO-d6) δ 8.74 (s, 1H), 8.51 (d, 1H, J=5.6 Hz), 8.41 (dd, 1H, J=10.7, 2.5 Hz), 8.15 (d, 1H, J=9.2 Hz), 7.53 (t, 1H, J=8.6 Hz), 7.09 (d, 1H, J=6.1 Hz), 6.86 (t, 1H, J=5.6 Hz), 3.39 (s, 2H), 3.24-3.14 (m, 2H), 3.07-2.98 (m, 2H), 2.94-2.87 (m, 2H), 2.37-2.26 (m, 1H), 1.33 (s, 9H); MS (ESI+): m/z 401.20 (100), [(M-C4H9)]+; m/z 457.20 (25), (M+H)+.

Workup

  1. concentrationthe mixture was concentrated under reduced pressure
  2. stirringstirred at rt for 2 h
  3. customThe reaction mixture was partitioned between EtOAc and saturated aq. NaHCO3 solution
  4. customthe EtOAc phase separated
  5. washwashed with brine
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by flash chromatography on SiO2 eluting with 1-5% MeOH/CH2Cl2

Sources & evidence

ORD record
ord-8288fd79525f40df84f48cd2628f4692
Source dataset
uspto-grants-2011_08
Patent number
US07989477B2

Reaction notes

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