Trifluoroacetic acid → Dibutyl[4-({4-[({2-[methyl(methylsulfonyl)amino]pyridin-3-yl}methyl)amino]-5-(trifluoromethyl)pyrimidin-2-yl}amino)benzyl]phosphonate trifluoroacetate

HRID 1947823Notes

Reaction equation

HRID 1947823 reaction equation
[CH2:1]([O:5][P:6]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([NH2:20])=[CH:16][CH:15]=1)(=[O:12])[O:7][CH2:8][CH2:9][CH2:10][CH3:11])[CH2:2][CH2:3][CH3:4].Cl[C:22]1[N:27]=[C:26]([NH:28][CH2:29][C:30]2[C:31]([N:36]([CH3:41])[S:37]([CH3:40])(=[O:39])=[O:38])=[N:32][CH:33]=[CH:34][CH:35]=2)[C:25]([C:42]([F:45])([F:44])[F:43])=[CH:24][N:23]=1.[C:46]([OH:52])([C:48]([F:51])([F:50])[F:49])=[O:47]>>[F:49][C:48]([F:51])([F:50])[C:46]([OH:52])=[O:47].[CH2:8]([O:7][P:6]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([NH:20][C:22]2[N:27]=[C:26]([NH:28][CH2:29][C:30]3[C:31]([N:36]([CH3:41])[S:37]([CH3:40])(=[O:39])=[O:38])=[N:32][CH:33]=[CH:34][CH:35]=3)[C:25]([C:42]([F:43])([F:45])[F:44])=[CH:24][N:23]=2)=[CH:16][CH:15]=1)(=[O:12])[O:5][CH2:1][CH2:2][CH2:3][CH3:4])[CH2:9][CH2:10][CH3:11]

Participants

4

Reactant 3

HCID 6422Trifluoroacetic acidHCID 22221324Dibutyl(4-aminobenzyl)phosphonateHCID 57584561N-(3-((2-chloro-5-(trifluoromethyl)pyrimidin-4-ylamino)methyl)pyridin-2-yl)-N-methylmethanesulfonamide

Product 1

HCID 86654004Dibutyl[4-({4-[({2-[methyl(methylsulfonyl)amino]pyridin-3-yl}methyl)amino]-5-(trifluoromethyl)pyrimidin-2-yl}amino)benzyl]phosphonate trifluoroacetateYield 73%

Conditions

Temperature
105 °C

Procedure

A mixture of dibutyl(4-aminobenzyl)phosphonate (18 mg, 0.06 mmol), N-[3-({[2-chloro-5-(trifluoromethyl)pyrimidin-4-yl]amino}methyl)pyridin-2-yl]-N-methylmethanesulfonamide XLIa (20 mg, 0.05 mmol), TFA (12 uL, 0.15 mmol) and TFE (0.5 mL) was heated at 105° C. under nitrogen in a microwave reactor for 40 minutes. The resulting mixture was concentrated in vacuo and the residue purified by preparative HPLC (MDP) to afford 24 mg of dibutyl[4-({4-[({2-[methyl(methylsulfonyl)amino]pyridin-3-yl}methyl)amino]-5-(trifluoromethyl)pyrimidin-2-yl}amino)benzyl]phosphonate trifluoroacetate (Example 26, yield 73%).

Workup

  1. concentrationThe resulting mixture was concentrated in vacuo
  2. customthe residue purified by preparative HPLC (MDP)

Sources & evidence

ORD record
ord-9321cc4fc0c848e4857e59d525c3a37f
Source dataset
uspto-grants-2013_03
Patent number
US08399433B2

Reaction notes

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