Cyclopropylamine → HCID 12012064, compound

HRID 2118089Notes

Reaction equation

HRID 2118089 reaction equation
[NH2:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[C@H:11]2[CH2:15][O:14][C@@H:13]([CH2:16][O:17][C:18](=[O:25])[C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[O:12]2)=[C:4](Cl)[N:3]=1.[CH:27]1([NH2:30])[CH2:29][CH2:28]1>C(O)C>[NH2:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[C@H:11]2[CH2:15][O:14][C@@H:13]([CH2:16][O:17][C:18](=[O:25])[C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[O:12]2)=[C:4]([NH:30][CH:27]2[CH2:29][CH2:28]2)[N:3]=1

Participants

4

Reactant 2

HCID 69828CyclopropylamineHCID 11749200HCID 11749200, compound

Product 1

HCID 12012064HCID 12012064, compoundYield 97.6%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Benzoic acid 4(R)-(2-amino-6-chloro-purin-9-yl)-[1,3]dioxolan-2(R)-ylmethyl ester (1266 g, cis/trans:1.9/1), ethanol (20 L), and cyclopropylamine (643 g) were refluxed for 16 hours. The reaction mixture was cooled and concentrated to a residue. The residue was dissolved in dichloromethane (3.6 L) and agitated with an aqueous solution of sodium bicarbonate for 30 minutes. After settling the organic layer was separated and the aqueous was back-extracted with dichloromethane (2×750 mL). The combined organic layers were concentrated to give a yellow-brown foam (1304 g) of material (9) which is suitable for reaction in the subsequent deprotection step in NH3/MeOH.

Workup

  1. temperatureThe reaction mixture was cooled
  2. concentrationconcentrated to a residue
  3. dissolutionThe residue was dissolved in dichloromethane (3.6 L)
  4. customwas separated
  5. extractionthe aqueous was back-extracted with dichloromethane (2×750 mL)
  6. concentrationThe combined organic layers were concentrated

Sources & evidence

ORD record
ord-d44eb5b3810a48d28b9894ca497e6b92
Source dataset
uspto-grants-2008_10
Patent number
US07442813B2

Reaction notes

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