Nitrogen → tert-butyl (1S,2R)-2-(6-carbamoyl-5-(5-fluoro-6-methylpyridin-2-ylamino)pyridazin-3-ylamino)cyclohexylcarbamate

HRID 1396375Notes

Reaction equation

HRID 1396375 reaction equation
Cl[C:2]1[N:7]=[N:6][C:5]([C:8]([NH2:10])=[O:9])=[C:4]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([F:18])=[C:14]([CH3:19])[N:13]=2)[CH:3]=1.[NH2:20][C@@H:21]1[CH2:26][CH2:25][CH2:24][CH2:23][C@@H:22]1[NH:27][C:28](=[O:34])[O:29][C:30]([CH3:33])([CH3:32])[CH3:31].N#N>CN1CCCC1=O.CN(C1C=CN=CC=1)C>[C:8]([C:5]1[N:6]=[N:7][C:2]([NH:20][C@@H:21]2[CH2:26][CH2:25][CH2:24][CH2:23][C@@H:22]2[NH:27][C:28](=[O:34])[O:29][C:30]([CH3:32])([CH3:31])[CH3:33])=[CH:3][C:4]=1[NH:11][C:12]1[CH:17]=[CH:16][C:15]([F:18])=[C:14]([CH3:19])[N:13]=1)(=[O:9])[NH2:10]

Participants

6

Reactant 3

HCID 947NitrogenHCID 1514389(1S,2R)-Cyclohexane-1,2-diamine, N1-BOC protectedHCID 86689737HCID 86689737, compound

Product 1

HCID 86689736tert-butyl (1S,2R)-2-(6-carbamoyl-5-(5-fluoro-6-methylpyridin-2-ylamino)pyridazin-3-ylamino)cyclohexylcarbamateYield 46.1%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
150 °C

Procedure

To a solution of 6-chloro-4-(5-fluoro-6-methylpyridin-2-ylamino) pyridazine-3-carboxamide (109 mg, 387 μmol) in N-methyl-2-pyrrolidinone (2.4 mL) was added DMAP (50.7 mg, 406 μmol) and tert-butyl (1S,2R)-2-aminocyclohexylcarbamate (166 mg, 774 μmol) and the mixture was heated to 150° C. for 1.5 d. A steam of N2 was blown into the mixture while still heating at 140° C. to evaporate the NMP, then the reaction mixture was purified by chromatography (silica, 50 μm, 40 g, Analogix, 97:2.75:0.15 to 84:15.2:0.8 dichloromethane:MeOH:NH4OH, 30 min) to provide tert-butyl (1S,2R)-2-(6-carbamoyl-5-(5-fluoro-6-methylpyridin-2-ylamino)pyridazin-3-ylamino)cyclohexylcarbamate (82 mg, 23%) as a brown oil. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 11.43 (s, 1H) 8.24 (s, 1H) 8.08 (br. s., 2H) 7.22-7.37 (m, 1H) 6.66-6.77 (m, 1H) 5.64 (d, J=3.28 Hz, 1H) 4.02 (br. s., 2H) 2.49 (d, J=3.03 Hz, 3H) 1.67-1.92 (m, 2H) 1.35-1.65 (m, 8H). LCMS (EI/CI) m/z: 460 [M+H].

Workup

  1. temperaturewhile still heating at 140° C.
  2. customto evaporate the NMP
  3. customthe reaction mixture was purified by chromatography (silica, 50 μm, 40 g, Analogix, 97:2.75:0.15 to 84:15.2:0.8 dichloromethane:MeOH:NH4OH, 30 min)

Sources & evidence

ORD record
ord-c718cca374e247498a55d77dd46dc5fb
Source dataset
uspto-grants-2014_12
Patent number
US08901124B2

Reaction notes

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