Diisopropylethylamine → tert-butyl (1S,2R)-2-(5-bromo-6-cyanopyridin-3-ylamino)cyclohexylcarbamate

HRID 1504850Notes

Reaction equation

HRID 1504850 reaction equation
[Br:1][C:2]1[C:3]([C:9]#[N:10])=[N:4][CH:5]=[C:6](F)[CH:7]=1.[NH2:11][C@@H:12]1[CH2:17][CH2:16][CH2:15][CH2:14][C@@H:13]1[NH:18][C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22].CCN(C(C)C)C(C)C>ClCCl>[Br:1][C:2]1[CH:7]=[C:6]([NH:11][C@@H:12]2[CH2:17][CH2:16][CH2:15][CH2:14][C@@H:13]2[NH:18][C:19](=[O:25])[O:20][C:21]([CH3:23])([CH3:22])[CH3:24])[CH:5]=[N:4][C:3]=1[C:9]#[N:10]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 1514389(1S,2R)-Cyclohexane-1,2-diamine, N1-BOC protectedHCID 469414773-Bromo-5-fluoropicolinonitrile

Product 1

HCID 86716545tert-butyl (1S,2R)-2-(5-bromo-6-cyanopyridin-3-ylamino)cyclohexylcarbamate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
110 °C

Procedure

To a flask were added 3-bromo-5-fluoropyridine-2-carbonitrile (14.8 g, 73.5 mmol), tert-butyl [(1S,2R)-2-aminocyclohexyl]carbamate (15 g, 70 mmol) and DIPEA (49 mL, 280 mmol). The resulting mixture was heated at 110° C. After 14 hours, the reaction mixture was cooled to room temperature, diluted with dichloromethane, absorbed on silica gel, and purified via silica gel chromatography to afford tert-butyl {(1S,2R)-2-[(5-bromo-6-cyanopyridin-3-yl)amino]cyclohexyl}carbamate. 1H NMR (600 MHz, DMSO-d6) δ 8.06 (s, 1H), 7.22 (s, 1H), 6.86 (d, J=7.8 Hz, 1H), 6.68 (d, J=7.8 Hz, 1H), 3.78 (s, 1H), 3.62 (s, 1H), 1.64-1.44 (m, 6H), 1.30 (s, 9), 1.14-1.08 (m, 2H).

Workup

  1. temperaturethe reaction mixture was cooled to room temperature
  2. customabsorbed on silica gel
  3. custompurified via silica gel chromatography

Sources & evidence

ORD record
ord-9572c0bd2f014044bfd5df953de3c467
Source dataset
uspto-grants-2015_12
Patent number
US09216173B2

Reaction notes

Loading…