Triethylamine → 6-(2-fluoro-5-((1R)-1-(4-(methylsulfonyl)-1-piperazinyl)ethyl)-3-pyridinyl)-N,N-bis(4-methoxybenzyl)-2-methyl-4-pyrimidinamine

HRID 1621879Notes

Reaction equation

HRID 1621879 reaction equation
[F:1][C:2]1[C:7]([C:8]2[N:13]=[C:12]([CH3:14])[N:11]=[C:10]([N:15]([CH2:25][C:26]3[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][CH:27]=3)[CH2:16][C:17]3[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=3)[CH:9]=2)=[CH:6][C:5]([C@H:34]([N:36]2[CH2:41][CH2:40][NH:39][CH2:38][CH2:37]2)[CH3:35])=[CH:4][N:3]=1.CCN(CC)CC.[CH3:49][S:50](Cl)(=[O:52])=[O:51].[OH-].[Na+]>C(Cl)Cl>[F:1][C:2]1[C:7]([C:8]2[N:13]=[C:12]([CH3:14])[N:11]=[C:10]([N:15]([CH2:16][C:17]3[CH:18]=[CH:19][C:20]([O:23][CH3:24])=[CH:21][CH:22]=3)[CH2:25][C:26]3[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][CH:27]=3)[CH:9]=2)=[CH:6][C:5]([C@H:34]([N:36]2[CH2:37][CH2:38][N:39]([S:50]([CH3:49])(=[O:52])=[O:51])[CH2:40][CH2:41]2)[CH3:35])=[CH:4][N:3]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 31297Methanesulfonyl chlorideHCID 685113046-(2-fluoro-5-((1R)-1-(1-piperazinyl)ethyl)-3-pyridinyl)-N,N-bis(4-methoxybenzyl)-2-methyl-4-pyrimidinamine

Product 1

HCID 685155046-(2-fluoro-5-((1R)-1-(4-(methylsulfonyl)-1-piperazinyl)ethyl)-3-pyridinyl)-N,N-bis(4-methoxybenzyl)-2-methyl-4-pyrimidinamineYield 62.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-20 °C

Procedure

A solution of 6-(2-fluoro-5-((1R)-1-(1-piperazinyl)ethyl)-3-pyridinyl)-N,N-bis(4-methoxybenzyl)-2-methyl-4-pyrimidinamine (0.448 g, 0.805 mmol) in CH2Cl2 (4 mL) at −20° C. was treated with NEt3 (1.122 mL, 8.05 mmol) followed by methanesulfonyl chloride (0.190 mL, 2.414 mmol). The mixture stirred at −20° C. for 30 minutes and then 1 M NaOH (aq.) and CH2Cl2 were added. The layers were separated and the aqueous layer was extracted with CH2Cl2 (2×). The crude material was adsorbed onto a plug of silica gel and purified by chromatography through a silica gel column (12 g), eluting with a gradient of 75% to 100% EtOAc in hexane, to provide 6-(2-fluoro-5-((1R)-1-(4-(methylsulfonyl)-1-piperazinyl)ethyl)-3-pyridinyl)-N,N-bis(4-methoxybenzyl)-2-methyl-4-pyrimidinamine (0.317 g, 0.499 mmol, 62.1% yield) as a white foam. m/z (ESI, +ve) 635.2 (M+H)+. 1H NMR (400 MHz, CDCl3) δ 8.46 (d, J=9.00 Hz, 1H); 8.18 (s, 1H); 7.17 (d, J=7.63 Hz, 4H); 6.83-6.89 (m, 5H); 4.74 (br. s., 4H); 3.80 (s, 6H); 3.65 (m, 1H); 3.18-3.30 (m, 4H); 2.77 (s, 3H); 2.64 (s, 5H); 2.50-2.58 (m, 2H); 1.44 (d, J=6.65 Hz, 3H).

Workup

  1. customThe layers were separated
  2. extractionthe aqueous layer was extracted with CH2Cl2 (2×)
  3. custompurified by chromatography through a silica gel column (12 g)
  4. washeluting with a gradient of 75% to 100% EtOAc in hexane

Sources & evidence

ORD record
ord-d372e1d1d29344a9a695ac1ae4cf53c0
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

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