Methanesulfonyl chloride → 2-Amino-5-(4-chloromethyl-2-methoxybenzyl)-6-methylpyrimidin-4-yl 2,4,6-triisopropylbenzenesulfonate

HRID 2207105Notes

Reaction equation

HRID 2207105 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([OH:8])[C:5]([CH2:9][C:10]2[CH:15]=[CH:14][C:13]([CH2:16]O)=[CH:12][C:11]=2[O:18][CH3:19])=[C:4]([CH3:20])[N:3]=1.C(N(CC)C(C)C)(C)C.[CH:30]([C:33]1[CH:38]=[C:37]([CH:39]([CH3:41])[CH3:40])[CH:36]=[C:35]([CH:42]([CH3:44])[CH3:43])[C:34]=1[S:45](Cl)(=[O:47])=[O:46])([CH3:32])[CH3:31].[Cl-].[Li+].CS([Cl:55])(=O)=O>O1CCCC1.O>[CH:42]([C:35]1[CH:36]=[C:37]([CH:39]([CH3:40])[CH3:41])[CH:38]=[C:33]([CH:30]([CH3:32])[CH3:31])[C:34]=1[S:45]([O:8][C:6]1[C:5]([CH2:9][C:10]2[CH:15]=[CH:14][C:13]([CH2:16][Cl:55])=[CH:12][C:11]=2[O:18][CH3:19])=[C:4]([CH3:20])[N:3]=[C:2]([NH2:1])[N:7]=1)(=[O:47])=[O:46])([CH3:43])[CH3:44]

Participants

8

Reactant 5

HCID 31297Methanesulfonyl chlorideHCID 810422,4,6-Tris(1-methylethyl)benzenesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 433294Lithium ChlorideHCID 178492557HCID 178492557, compound

Product 1

HCID 1179927752-Amino-5-(4-chloromethyl-2-methoxybenzyl)-6-methylpyrimidin-4-yl 2,4,6-triisopropylbenzenesulfonateYield 66.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-amino-5-(4-hydroxymethyl-2-methoxybenzyl)-6-methylpyrimidin-4-ol (5.0 g) and N,N-diisopropylethylamine (11.7 g) in tetrahydrofuran (50 g), 2,4,6-triisopropylbenzenesulfonyl chloride (8.3 g) was added and refluxed for 10 h. After cooling to RT, lithium chloride (2.3 g) was added to the reaction mixture and stirred for 0.5 h, methanesulfonyl chloride (4.2 g) was added over 0.25 h dropwise and the reaction mixture was stirred for 4 h at RT. To the reaction mixture, water (25 g) was added and extracted with ethyl acetate (25 g). The organic layer was washed with water (25 mL) and concentrated in vacuo. To the residue, toluene (20 g) was added and concentrated on vacuo to obtain a light brown solid. The solid was precipitated with toluene (30 g) to obtain sub-title compound (6.8 g). 1H-NMR (300 MHz, CDCl3) δ 7.17 (2H, s), 6.90-6.82 (3H, m), 5.16 (2H, brs), 4.55 (2H, s), 4.10 (2H, septet, J=6.8 Hz), 3.82 (3H, s), 3.81 (2H, s), 2.91 (1H, septet, J=6.8 Hz), 2.32 (3H, s), 1.25 (6H, d, J=7.2 Hz), 1.19 (12H, d, J=6.8 Hz)

Workup

  1. temperaturerefluxed for 10 h
  2. stirringthe reaction mixture was stirred for 4 h at RT
  3. extractionextracted with ethyl acetate (25 g)
  4. washThe organic layer was washed with water (25 mL)
  5. concentrationconcentrated in vacuo
  6. additionTo the residue, toluene (20 g) was added
  7. concentrationconcentrated on vacuo
  8. customto obtain a light brown solid
  9. customThe solid was precipitated with toluene (30 g)

Sources & evidence

ORD record
ord-d2d4a30109c24b33aac73bffec4f2ed0
Source dataset
uspto-grants-2016_06
Patent number
US09376398B2

Reaction notes

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