tert-Butyl bromoacetate → (4-{[5-Nitro-2-(2-trifluoromethoxy-benzylamino)-pyrimidin-4-ylamino]-methyl}-cyclohexylamino)-acetic acid tert-butyl ester

HRID 1819483Notes

Reaction equation

HRID 1819483 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.Br[CH2:42][C:43]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44]>CN(C=O)C.CS(C)=O>[C:46]([O:45][C:43](=[O:44])[CH2:42][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)([CH3:49])([CH3:48])[CH3:47]

Participants

5

Reactant 3

HCID 79177tert-Butyl bromoacetateHCID 81531DiisopropylethylamineHCID 16202211N4-(4-amino-cyclohexylmethyl)-5-nitro-N2-(2-trifluoromethoxy-benzyl)-pyrimidine-2,4-diamine

Product 1

HCID 69053878(4-{[5-Nitro-2-(2-trifluoromethoxy-benzylamino)-pyrimidin-4-ylamino]-methyl}-cyclohexylamino)-acetic acid tert-butyl esterYield 61.3%

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 (88 mg, 0.20 mmol) in 2:1 DMF/DMSO (0.6 mL) was added N,N-diisopropylethylamine (35 μL, 0.30 mmol) followed by tert-butyl bromoacetate (22 μL, 0.15 mmol). The mixture was stirred at room temperature overnight then partitioned with EtOAc (15 mL) and water (5 mL). The layers were separated and the organics washed with water (2×5 mL) and brine. After concentration in vacuo, the residue was purified by column chromatography (silica gel, 97:3 DCM/MeOH) to afford (4-{[5-nitro-2-(2-trifluoromethoxy-benzylamino)-pyrimidin-4-ylamino]-methyl}-cyclohexylamino)-acetic acid tert-butyl ester (51 mg, 61%) as a colorless oil, m/z 555 [M+1]+.

Workup

  1. customthen partitioned with EtOAc (15 mL) and water (5 mL)
  2. customThe layers were separated
  3. washthe organics washed with water (2×5 mL) and brine
  4. concentrationAfter concentration in vacuo
  5. customthe residue was purified by column chromatography (silica gel, 97:3 DCM/MeOH)

Sources & evidence

ORD record
ord-01f1644b292047429d4808ea50015edf
Source dataset
uspto-grants-2009_10
Patent number
US07601714B2

Reaction notes

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