2,4-Dichloropyrimidine-5-carboxamide → (7R,8aS)-N-(5-aminocarbonyl-2-chloropyrimidin-4-yl)-octahydro-5,5-dimethylindolizin-7-amine

HRID 633382Notes

Reaction equation

HRID 633382 reaction equation
[CH3:1][C:2]1([CH3:12])[CH2:10][C@H:9]([NH2:11])[CH2:8][C@H:7]2[N:3]1[CH2:4][CH2:5][CH2:6]2.[NH2:13][C:14]([C:16]1[C:17](Cl)=[N:18][C:19]([Cl:22])=[N:20][CH:21]=1)=[O:15]>CC(O)C>[NH2:13][C:14]([C:16]1[C:17]([NH:11][C@@H:9]2[CH2:8][C@H:7]3[N:3]([CH2:4][CH2:5][CH2:6]3)[C:2]([CH3:12])([CH3:1])[CH2:10]2)=[N:18][C:19]([Cl:22])=[N:20][CH:21]=1)=[O:15]

Participants

4

Reactant 2

HCID 212230802,4-Dichloropyrimidine-5-carboxamideHCID 86704446(7R,8aS)-octahydro-5,5-dimethylindolizin-7-amine

Product 1

HCID 86704482(7R,8aS)-N-(5-aminocarbonyl-2-chloropyrimidin-4-yl)-octahydro-5,5-dimethylindolizin-7-amineYield 54%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

A mixture of (7R,8aS)-octahydro-5,5-dimethylindolizin-7-amine (1.25 g) and 5-aminocarbonyl-2,4-dichloropyrimidine (2.14 g, 1.5 eq.) in iPrOH (50 mL) was stirred at −10° C. to rt for 3 d. The solid was filtered off and washed with methanol (3×10 mL). The filtrate was evaporated under vacuum and the residue was purified by CombiFlash chromatography on silica gel (2N NH3 in MeOH/CH2Cl2=0-30%) to give the desired product (1.3 g, 54% over 3 steps).

Workup

  1. filtrationThe solid was filtered off
  2. washwashed with methanol (3×10 mL)
  3. customThe filtrate was evaporated under vacuum
  4. customthe residue was purified by CombiFlash chromatography on silica gel (2N NH3 in MeOH/CH2Cl2=0-30%)

Sources & evidence

ORD record
ord-1aeca85dcf184442ae8ba4ab35a9cefe
Source dataset
uspto-grants-2016_04
Patent number
US09321763B2

Reaction notes

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