Ethyl1-[[(2-chloro-5-nitro-pyrimidin-4-yl)-propan-2-yl-amino]methyl]cyclopropane-1-carboxylate → 2'-chloro-9'-isopropyl-8',9'-dihydrospiro[cyclopropane-1,7'-pyrimido[5,4-b][1,4]diazepin]-6'(5'H)-one

HRID 2234476Notes

Reaction equation

HRID 2234476 reaction equation
C([O:3][C:4]([C:6]1([CH2:9][N:10]([C:14]2[C:19]([N+:20]([O-])=O)=[CH:18][N:17]=[C:16]([Cl:23])[N:15]=2)[CH:11]([CH3:13])[CH3:12])[CH2:8][CH2:7]1)=O)C>C(O)(=O)C.[Fe]>[Cl:23][C:16]1[N:17]=[CH:18][C:19]2[NH:20][C:4](=[O:3])[C:6]3([CH2:8][CH2:7]3)[CH2:9][N:10]([CH:11]([CH3:13])[CH3:12])[C:14]=2[N:15]=1

Participants

4

Reactant 1

HCID 86617588Ethyl1-[[(2-chloro-5-nitro-pyrimidin-4-yl)-propan-2-yl-amino]methyl]cyclopropane-1-carboxylate2×

Product 1

HCID 866175872'-chloro-9'-isopropyl-8',9'-dihydrospiro[cyclopropane-1,7'-pyrimido[5,4-b][1,4]diazepin]-6'(5'H)-one

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 176Acetic AcidSolvent

Conditions

Temperature
70 °C

Procedure

Ethyl1-[[(2-chloro-5-nitro-pyrimidin-4-yl)-propan-2-yl-amino]methyl]cyclopropane-1-carboxylate (Intermediate 208; 10.26 g, 30 mmol) was dissolved in acetic acid (500 mL) and heated to 70° C. Iron powder (6 g) was added in portions over 10 minutes. The mixture was stirred at 70° C. for 3 hours. The reaction mixture was filtered hot through celite, and the pad washed with DCM. The filtrate was evaporated to dryness then sonicated in saturated aqueous sodium hydrogen carbonate solution to give a brown suspension. This was filtered, and the resulting solid washed with water. The solid was then sucked dry on a filter, and suspended in a small amount of methanol with sonication. The methanol suspension was then diluted with DCM (10× excess), and filtered to give a yellow solution, which was dried over sodium sulphate, then concentrated in vacuo to give a yellow/green solid. The solid was triturated under cold methanol to yield the title compound as a white powder. (5 g, 63%)

Workup

  1. filtrationThe reaction mixture was filtered hot through celite
  2. washthe pad washed with DCM
  3. customThe filtrate was evaporated to dryness
  4. customthen sonicated in saturated aqueous sodium hydrogen carbonate solution
  5. customto give a brown suspension
  6. filtrationThis was filtered
  7. washthe resulting solid washed with water
  8. customThe solid was then sucked dry on a filter
  9. customsuspended in a small amount of methanol with sonication
  10. additionThe methanol suspension was then diluted with DCM (10× excess)
  11. filtrationfiltered
  12. customto give a yellow solution, which
  13. dry with materialwas dried over sodium sulphate
  14. concentrationconcentrated in vacuo
  15. customto give a yellow/green solid
  16. customThe solid was triturated under cold methanol

Sources & evidence

ORD record
ord-682f201d97f548f4a0034488804a48f1
Source dataset
uspto-grants-2010_05
Patent number
US07709471B2

Reaction notes

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