Diisopropylethylamine → [4-({2-[(2-Isopropoxy-pyridin-3-ylmethyl)-amino]-5-nitro-pyrimidin-4-ylamino}-methyl)-cyclohexyl]-carbamic acid tert-butyl ester

HRID 1819440Notes

Reaction equation

HRID 1819440 reaction equation
[C:1]([O:5][C:6](=[O:26])[NH:7][CH:8]1[CH2:13][CH2:12][CH:11]([CH2:14][NH:15][C:16]2[C:21]([N+:22]([O-:24])=[O:23])=[CH:20][N:19]=[C:18](Cl)[N:17]=2)[CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[CH:27]([O:30][C:31]1[C:36](NC)=[CH:35][CH:34]=[CH:33][N:32]=1)([CH3:29])[CH3:28].C[CH2:40][N:41](C(C)C)C(C)C>CN(C=O)C.C(OCC)(=O)C>[C:1]([O:5][C:6](=[O:26])[NH:7][CH:8]1[CH2:13][CH2:12][CH:11]([CH2:14][NH:15][C:16]2[C:21]([N+:22]([O-:24])=[O:23])=[CH:20][N:19]=[C:18]([NH:41][CH2:40][C:36]3[C:31]([O:30][CH:27]([CH3:28])[CH3:29])=[N:32][CH:33]=[CH:34][CH:35]=3)[N:17]=2)[CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 57885529(4-[(2-Chloro-5-nitro-pyrimidin-4-ylamino)-methyl]cyclohexyl)-carbamic acid tert-butyl esterHCID 61379578(2-Isopropoxy-pyridin-3-yl)-methylamine

Product 1

HCID 69063737[4-({2-[(2-Isopropoxy-pyridin-3-ylmethyl)-amino]-5-nitro-pyrimidin-4-ylamino}-methyl)-cyclohexyl]-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of {4-[(2-chloro-5-nitro-pyrimidin-4-ylamino)-methyl]-cyclohexyl}-carbamic acid tert-butyl ester (150 mg, 0.39 mmol) in DMF (1 mL) were added a solution of (2-isopropoxy-pyridin-3-yl)-methylamine (180 mg, 1.1 mmol) obtained above in DMF (1 mL) followed by DIPEA (135 μL, 0.78 mmol). The reaction mixture was stirred at room temperature for 30 min. The reaction mixture was diluted with ethyl acetate and washed with saturated NaHCO3 and water (×4). The organic phase was dried over Na2SO4 and concentrated. The resulting residue was purified by silica gel prep TLC using 95:5 CH2Cl2:MeOH as an eluent to afford [4-({2-[(2-isopropoxy-pyridin-3-ylmethyl)-amino]-5-nitro-pyrimidin-4-ylamino}-methyl)-cyclohexyl]-carbamic acid tert-butyl ester which was dissolved in CH2Cl2 and TFA was added. The reaction mixture was stirred at room temperature for 2 h. The mixture was then treated with 1M Na2CO3 and extracted with CH2Cl2. MeOH was added to the mixture during the extraction to solublize the product into the organic phase. The combined organic phase was dried over Na2SO4 and concentrated. The resulting residue was purified by silica gel prep TLC using 10:1:0.2 CH2Cl2:MeOH:NH4OH as an eluent to afford 75 mg of the title compound as a pale yellow solid (46%); m/z 416.4 [M+1]+.

Workup

  1. washwashed with saturated NaHCO3 and water (×4)
  2. dry with materialThe organic phase was dried over Na2SO4
  3. concentrationconcentrated
  4. customThe resulting residue was purified by silica gel prep TLC

Sources & evidence

ORD record
ord-42b0a7d5290745d2ae7a859c09a4d943
Source dataset
uspto-grants-2009_10
Patent number
US07601714B2

Reaction notes

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