2-Amino-5-chloropyridine → HCID 66705878, compound

HRID 2276373Notes

Reaction equation

HRID 2276373 reaction equation
NC1C=CC(Cl)=CN=1.ClC(Cl)(OC(=O)OC(Cl)(Cl)Cl)Cl.[Cl-].C([NH+](CC)CC)C.[Cl:29][C:30]1[CH:31]=[CH:32][C:33]([N:36]=[C:37]=[O:38])=[N:34][CH:35]=1.[NH2:39][C:40]1[CH:45]=[CH:44][C:43]([CH:46]2[CH2:50][CH2:49][N:48]([C:51]([O:53][C:54]([CH3:57])([CH3:56])[CH3:55])=[O:52])[CH2:47]2)=[CH:42][CH:41]=1.C(N(CC)C(C)C)(C)C>ClC(Cl)C.ClCCl.C(N(CC)CC)C>[C:54]([O:53][C:51]([N:48]1[CH2:49][CH2:50][CH:46]([C:43]2[CH:44]=[CH:45][C:40]([NH:39][C:37]([NH:36][C:33]3[CH:32]=[CH:31][C:30]([Cl:29])=[CH:35][N:34]=3)=[O:38])=[CH:41][CH:42]=2)[CH2:47]1)=[O:52])([CH3:57])([CH3:55])[CH3:56]

Participants

10

Reactant 6

HCID 661742-Amino-5-chloropyridineHCID 81531DiisopropylethylamineHCID 94429TriphosgeneHCID 12698378Triethylazanium chlorideHCID 205331395-Chloro-2-isocyanatopyridineHCID 573650691,1-Dimethylethyl 3-(4-aminophenyl)-1-pyrrolidinecarboxylate

Product 1

HCID 66705878HCID 66705878, compoundYield 38%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 63651,1-DichloroethaneSolvent2×HCID 8471TriethylamineSolvent

Conditions

Temperature
50 °C

Procedure

To a stirred suspension of 2-amino-5-chloro-pyridine (1.01 g) in dichloroethane (20 ml) was added portionwise triphosgene (831 mg). Triethylamine (2.22 ml) was then added dropwise and the mixture was stirred at 50° C. for 1 h. The mixture was then concentrated in vacuo to afford a beige solid containing a mixture of triethylammonium chloride and 5-chloro-2-isocyanato-pyridine. This solid was then added to a stirred solution of (RS)-tert-butyl 3-(4-aminophenyl)pyrrolidine-1-carboxylate (350 mg, CAS 908334-28-1) and N,N-diisopropylethylamine (0.68 ml) in dichloroethane (6 ml) and the resulting mixture was stirred at 60° C. overnight. The mixture was then diluted with dichloromethane and washed with water. The phases were separated and the organic phase was dried over sodium sulphate and concentrated in vacuo. The residue was purified by column chromatography (SiO2; gradient: heptane/EtOAc) to give (RS)-3-{4-[3-(5-chloro-pyridin-2-yl)-ureido]-phenyl}-pyrrolidine-1-carboxylic acid tert-butyl ester (212 mg, 38%) as an off-white solid. MS (ISP): 419.2 ([{37Cl}M+H]+), 417.2 ([{35Cl}M+H]+).

Workup

  1. concentrationThe mixture was then concentrated in vacuo
  2. customto afford a beige solid
  3. additioncontaining
  4. stirringthe resulting mixture was stirred at 60° C. overnight
  5. washwashed with water
  6. customThe phases were separated
  7. dry with materialthe organic phase was dried over sodium sulphate
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by column chromatography (SiO2; gradient: heptane/EtOAc)

Sources & evidence

ORD record
ord-e1aa8b0cb4d34d5cb5acc0a7b471a382
Source dataset
uspto-grants-2015_09
Patent number
US09132136B2

Reaction notes

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