Diisopropylethylamine → [4-({2-[(Isoquinolin-1-ylmethyl)-amino]-5-nitro-pyrimidin-4-ylamino}-methyl)-cyclohexyl]-carbamic acid tert-butyl ester

HRID 1819448Notes

Reaction equation

HRID 1819448 reaction equation
[C:1]1(NC)[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][N:2]=1.[CH:13]([N:16](C(C)C)CC)(C)C.[C:22]([O:26][C:27](=[O:47])[NH:28][CH:29]1[CH2:34][CH2:33][CH:32]([CH2:35][NH:36][C:37]2[C:42]([N+:43]([O-:45])=[O:44])=[CH:41][N:40]=[C:39](Cl)[N:38]=2)[CH2:31][CH2:30]1)([CH3:25])([CH3:24])[CH3:23]>CN(C=O)C>[C:22]([O:26][C:27](=[O:47])[NH:28][CH:29]1[CH2:34][CH2:33][CH:32]([CH2:35][NH:36][C:37]2[C:42]([N+:43]([O-:45])=[O:44])=[CH:41][N:40]=[C:39]([NH:16][CH2:13][C:1]3[C:10]4[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=4)[CH:4]=[CH:3][N:2]=3)[N:38]=2)[CH2:31][CH2:30]1)([CH3:25])([CH3:24])[CH3:23]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 22978454N-methylisoquinolin-1-amineHCID 57885529(4-[(2-Chloro-5-nitro-pyrimidin-4-ylamino)-methyl]cyclohexyl)-carbamic acid tert-butyl ester

Product 1

HCID 57885587[4-({2-[(Isoquinolin-1-ylmethyl)-amino]-5-nitro-pyrimidin-4-ylamino}-methyl)-cyclohexyl]-carbamic acid tert-butyl esterYield 83.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of isoquinolin-1-yl-methylamine (1.32 g, 8.35 mmol) and diisopropylethylamine (2.7 mL, 15.5 mmol) in DMF (20 mL) was added {4-[(2-chloro-5-nitro-pyrimidin-4-ylamino)-methyl]-cyclohexyl}-carbamic acid tert-butyl ester (1.5 g, 3.89 mmol). The reaction mixture was stirred at room temperature for 10 min. The solvent was removed and the resulting residue was diluted with a mixture of ethyl acetate (350 mL) and CH2Cl2 (100 mL). The solution was then washed with 1M Na2CO3 and water. The organic phase was dried over Na2SO4 and concentrated. The resulting solid was treated with ethyl acetate (poor solubility of the product in ethyl acetate) and the un-dissolved solid was filtered through a Buchner funnel. The white solid was dried in vacuo to yield 1.64 g of [4-({2-[(isoquinolin-1-ylmethyl)-amino]-5-nitro-pyrimidin-4-ylamino}-methyl)-cyclohexyl]-carbamic acid tert-butyl ester.

Workup

  1. customThe solvent was removed
  2. additionthe resulting residue was diluted with a mixture of ethyl acetate (350 mL) and CH2Cl2 (100 mL)
  3. washThe solution was then washed with 1M Na2CO3 and water
  4. dry with materialThe organic phase was dried over Na2SO4
  5. concentrationconcentrated
  6. additionThe resulting solid was treated with ethyl acetate (poor solubility of the product in ethyl acetate) and the un-dissolved solid
  7. filtrationwas filtered through a Buchner funnel
  8. customThe white solid was dried in vacuo

Sources & evidence

ORD record
ord-39469635163d440cb37b3cc4a80a7fb9
Source dataset
uspto-grants-2009_10
Patent number
US07601714B2

Reaction notes

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