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

HRID 1812290Notes

Reaction equation

HRID 1812290 reaction equation
[CH3:1][O:2][C:3]1[CH:49]=[CH:48][C:6]([CH2:7][N:8]([CH2:39][C:40]2[CH:45]=[CH:44][C:43]([O:46][CH3:47])=[CH:42][CH:41]=2)[C:9]2[N:14]=[C:13]([CH3:15])[N:12]=[C:11]([C:16]3[CH:17]=[C:18]([C@H:23]([N:25]4[CH2:30][CH2:29][N:28](C(OC(C)(C)C)=O)[CH2:27][C@@H:26]4[CH3:38])[CH3:24])[CH:19]=[N:20][C:21]=3[F:22])[CH:10]=2)=[CH:5][CH:4]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[F:22][C:21]1[C:16]([C:11]2[N:12]=[C:13]([CH3:15])[N:14]=[C:9]([N:8]([CH2:7][C:6]3[CH:48]=[CH:49][C:3]([O:2][CH3:1])=[CH:4][CH:5]=3)[CH2:39][C:40]3[CH:41]=[CH:42][C:43]([O:46][CH3:47])=[CH:44][CH:45]=3)[CH:10]=2)=[CH:17][C:18]([C@H:23]([N:25]2[CH2:30][CH2:29][NH:28][CH2:27][C@@H:26]2[CH3:38])[CH3:24])=[CH:19][N:20]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 68517227tert-butyl (3S)-4-((1R)-1-(5-(6-(bis(4-methoxybenzyl)amino)-2-methyl-4-pyrimidinyl)-6-fluoro-3-pyridinyl)ethyl)-3-methyl-1-piperazinecarboxylate

Product 1

HCID 685158656-(2-fluoro-5-((1R)-1-((2S)-2-methyl-1-piperazinyl)ethyl)-3-pyridinyl)-N,N-bis(4-methoxybenzyl)-2-methyl-4-pyrimidinamineYield 98%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of tert-butyl (3S)-4-((1R)-1-(5-(6-(bis(4-methoxybenzyl)amino)-2-methyl-4-pyrimidinyl)-6-fluoro-3-pyridinyl)ethyl)-3-methyl-1-piperazinecarboxylate (0.240 g, 0.358 mmol) in CH2Cl2 (5 mL) at 0° C. was treated with TFA (0.53 mL, 7.16 mmol). The reaction was allowed to warm up to RT and stir for 2 hours. The reaction mixture was concentrated, resuspended in CH2Cl2 and treated with aqueous NaHCO3 (sat.). The layers were separated and the aqueous layer was extracted with CH2Cl2 (2×). The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated to give 6-(2-fluoro-5-((1R)-1-((2S)-2-methyl-1-piperazinyl)ethyl)-3-pyridinyl)-N,N-bis(4-methoxybenzyl)-2-methyl-4-pyrimidinamine (0.200 g, 0.350 mmol, 98% yield) as a light yellow oil. m/z (ESI, +ve) 571.3 (M+H)+. 1H NMR (400 MHz, CDCl3) δ 8.39 (dd, J=9.39, 2.35 Hz, 1H); 8.12 (s, 1H); 7.18 (d, J=7.82 Hz, 4H); 6.79-6.89 (m, 5H); 4.74 (br. s., 4H); 4.16 (q, J=6.98 Hz, 1H); 3.79 (s, 6H); 2.80-2.99 (m, 4H); 2.53-2.63 (m, 4H); 2.23-2.41 (m, 2H); 1.47 (s, 3H); 1.08 (d, J=6.26 Hz, 3H).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. additiontreated with aqueous NaHCO3 (sat.)
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with CH2Cl2 (2×)
  5. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-96d4ebc1845c40178b59f76fc5049672
Source dataset
uspto-grants-2013_01
Patent number
US08362241B2

Reaction notes

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