Diisopropylethylamine → (R)-benzyl 1-(1-(6-chloro-5-cyano-3-fluoropyridin-2-ylamino)propyl)cyclopropylcarbamate

HRID 2201145Notes

Reaction equation

HRID 2201145 reaction equation
[Cl:1][C:2]1[N:10]=[C:9](Cl)[C:8]([F:12])=[CH:7][C:3]=1[C:4]([NH2:6])=O.Cl.[CH2:14]([O:21][C:22](=[O:31])[NH:23][C:24]1([C@H:27]([NH2:30])[CH2:28][CH3:29])[CH2:26][CH2:25]1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.CCN(C(C)C)C(C)C>CN1C(=O)CCC1.CCOC(C)=O>[Cl:1][C:2]1[N:10]=[C:9]([NH:30][C@@H:27]([C:24]2([NH:23][C:22](=[O:31])[O:21][CH2:14][C:15]3[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=3)[CH2:26][CH2:25]2)[CH2:28][CH3:29])[C:8]([F:12])=[CH:7][C:3]=1[C:4]#[N:6]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 27740222,6-Dichloro-5-fluoronicotinamideHCID 86666166(R)-benzyl-1-(1-aminopropyl)cyclopropylcarbamate hydrochloride

Product 1

HCID 86666165(R)-benzyl 1-(1-(6-chloro-5-cyano-3-fluoropyridin-2-ylamino)propyl)cyclopropylcarbamateYield 44.8%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 2,6-dichloro-5-fluoronicotinamide (233 mg, 1.22 mmol) in NMP (5.0 mL) was added (R)-benzyl-1-(1-aminopropyl)cyclopropylcarbamate hydrochloride salt (350 mg, 1.23 mmol) and DIPEA (0.434 mL, 2.44 mmol). After heated at 80° C. for 4 h, the mixture was diluted with EtOAc, organic layer was washed brine, dried and concentrated to give (R)-benzyl 1-(1-(6-chloro-5-cyano-3-fluoropyridin-2-ylamino)propyl)cyclopropylcarbamate (220 mg).

Workup

  1. washwas washed brine
  2. customdried
  3. concentrationconcentrated

Sources & evidence

ORD record
ord-6af93425e4d44c41a5c8b90596cb676d
Source dataset
uspto-grants-2016_06
Patent number
US09359375B2

Reaction notes

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