Diisopropylethylamine → 4-(4-{[5-Nitro-2-(2-trifluoromethoxy-benzylamino)-pyrimidin-4-ylamino]-methyl}-cyclohexylamino)-butyric acid methyl ester

HRID 1819485Notes

Reaction equation

HRID 1819485 reaction equation
[NH2:1][CH:2]1[CH2:7][CH2:6][CH:5]([CH2:8][NH:9][C:10]2[C:15]([N+:16]([O-:18])=[O:17])=[CH:14][N:13]=[C:12]([NH:19][CH2:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=3[O:27][C:28]([F:31])([F:30])[F:29])[N:11]=2)[CH2:4][CH2:3]1.C(N(CC)C(C)C)(C)C.[CH3:41][O:42][C:43](=[O:48])[CH2:44][CH2:45][CH2:46]I>CN(C=O)C.CS(C)=O>[CH3:41][O:42][C:43](=[O:48])[CH2:44][CH2:45][CH2:46][NH:1][CH:2]1[CH2:3][CH2:4][CH:5]([CH2:8][NH:9][C:10]2[C:15]([N+:16]([O-:18])=[O:17])=[CH:14][N:13]=[C:12]([NH:19][CH2:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=3[O:27][C:28]([F:30])([F:31])[F:29])[N:11]=2)[CH2:6][CH2:7]1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 547991Methyl 4-iodobutanoateHCID 16202211N4-(4-amino-cyclohexylmethyl)-5-nitro-N2-(2-trifluoromethoxy-benzyl)-pyrimidine-2,4-diamine

Product 1

HCID 578856074-(4-{[5-Nitro-2-(2-trifluoromethoxy-benzylamino)-pyrimidin-4-ylamino]-methyl}-cyclohexylamino)-butyric acid methyl esterYield 53.1%

Reagents, catalysts & solvents 1

HCID 3013483N,N-dimethylformamide; methylsulfinylmethaneSolvent

Procedure

To a solution of N4-(4-amino-cyclohexylmethyl)-5-nitro-N2-(2-trifluoromethoxy-benzyl)-pyrimidine-2,4-diamine (80 mg, 0.182 mmol) in 2:1 DMF/DMSO (0.6 mL) was added N,N-diisopropylethylamine (32 μL, 0.272 mmol) followed by methyl-4-iodobutyrate (19 μL, 0.136 mmol). The mixture was stirred at room temperature overnight then partitioned with EtOAc (15 mL) and water (10 mL). The layers were separated and the organics dried over Na2SO4. After concentration in vacuo, the residue was purified by column chromatography using a 12 g ISCO combi-flash cartridge (silica gel, 100:0 to 90:10 DCM/MeOH) to afford 4-(4-{[5-nitro-2-(2-trifluoromethoxy-benzylamino)-pyrimidin-4-ylamino]-methyl}-cyclohexylamino)-butyric acid methyl ester (39 mg, 53%) as a white solid: m/z 541 [M+1]+.

Workup

  1. customthen partitioned with EtOAc (15 mL) and water (10 mL)
  2. customThe layers were separated
  3. dry with materialthe organics dried over Na2SO4
  4. concentrationAfter concentration in vacuo
  5. customthe residue was purified by column chromatography

Sources & evidence

ORD record
ord-e39b98488dd8415bab562eea564c5361
Source dataset
uspto-grants-2009_10
Patent number
US07601714B2

Reaction notes

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