Dimethylamine → {1-[1-(5-Iodo-pyrimidin-2-yl)-cyclopropylcarbamoyl]-cyclopropyl}-carbamic acid tert-butyl ester

HRID 2038767Notes

Reaction equation

HRID 2038767 reaction equation
Cl.[C:2]([O:6][C:7](=[O:21])[NH:8][C:9]1([C:12](=[O:20])[NH:13][C:14]2([C:17](=[NH:19])[NH2:18])[CH2:16][CH2:15]2)[CH2:11][CH2:10]1)([CH3:5])([CH3:4])[CH3:3].CN(C)[CH:24]=[C:25]([I:28])[CH:26]=O.CNC.C1COCC1>CCO.CCOCC>[C:2]([O:6][C:7](=[O:21])[NH:8][C:9]1([C:12](=[O:20])[NH:13][C:14]2([C:17]3[N:18]=[CH:26][C:25]([I:28])=[CH:24][N:19]=3)[CH2:16][CH2:15]2)[CH2:10][CH2:11]1)([CH3:5])([CH3:3])[CH3:4]

Participants

7

Reactant 4

HCID 674DimethylamineHCID 8028TetrahydrofuranHCID 68379067[1-(1-Carbamimidoyl-cyclopropylcarbamoyl)-cyclopropyl]-carbamic acid tert-butyl ester hydrochlorideHCID 713174763-(Dimethylamino)-2-iodoprop-2-enal

Product 1

HCID 67508490{1-[1-(5-Iodo-pyrimidin-2-yl)-cyclopropylcarbamoyl]-cyclopropyl}-carbamic acid tert-butyl esterYield 18.4%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 3283Diethyl EtherSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of [1-(1-carbamimidoyl-cyclopropylcarbamoyl)-cyclopropyl]-carbamic acid tert-butyl ester hydrochloride (1.65 g, 5.2 mmol) in anhydrous EtOH (21 mL), was added 3-dimethylamino-2-iodo-propenal (1.3 g, 5.63 mmol) and 2M dimethylamine in THF (3.36 mL, 6.7 mmol). The vessel was capped and heated at 70° C. overnight. After 18 h, EtOH was removed in-vacuo and the dark orange residue was triturated with 5% iPrOH in EtOAc. A yellow solid was filtered off. The filtrate was concentrated in vacuo and purified by normal phase flash chromatography on silica gel (0→5% MeOH/CH2Cl2) to yield a black oil. This oil was treated with Et2O to precipitate a white solid. The solid was filtered off and the filtrate was reprocessed to give another crop of slightly darker solids. A total of 426 mg of {1-[1-(5-iodo-pyrimidin-2-yl)-cyclopropylcarbamoyl]-cyclopropyl}-carbamic acid tert-butyl ester was isolated, m/z 445.5 [M+H]+.

Workup

  1. customThe vessel was capped
  2. customEtOH was removed in-vacuo
  3. customthe dark orange residue was triturated with 5% iPrOH in EtOAc
  4. filtrationA yellow solid was filtered off
  5. concentrationThe filtrate was concentrated in vacuo
  6. custompurified by normal phase flash chromatography on silica gel (0→5% MeOH/CH2Cl2)
  7. customto yield a black oil
  8. customto precipitate a white solid
  9. filtrationThe solid was filtered off
  10. customto give another crop of slightly darker solids

Sources & evidence

ORD record
ord-6dd1e19e370342c1829ab32d6668c1dd
Source dataset
uspto-grants-2013_11
Patent number
US08575360B2

Reaction notes

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