Methanol → HCID 86689753, compound

HRID 1396398Notes

Reaction equation

HRID 1396398 reaction equation
[C:1]([C:5]1[N:10]=[C:9]([NH:11][C:12]2[CH:17]=[C:16](Cl)[N:15]=[N:14][C:13]=2[C:19]([NH2:21])=[O:20])[CH:8]=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[NH2:22][C@@H:23]1[CH2:28][CH2:27][CH2:26][CH2:25][C@@H:24]1[NH:29][C:30](=[O:36])[O:31][C:32]([CH3:35])([CH3:34])[CH3:33].CO.C(Cl)Cl>CN1C(=O)CCC1>[NH4+:10].[OH-:20].[C:1]([C:5]1[N:10]=[C:9]([NH:11][C:12]2[CH:17]=[C:16]([NH:22][C@@H:23]3[CH2:28][CH2:27][CH2:26][CH2:25][C@@H:24]3[NH:29][C:30](=[O:36])[O:31][C:32]([CH3:34])([CH3:33])[CH3:35])[N:15]=[N:14][C:13]=2[C:19](=[O:20])[NH2:21])[CH:8]=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 887MethanolHCID 6344DichloromethaneHCID 1514389(1S,2R)-Cyclohexane-1,2-diamine, N1-BOC protectedHCID 86689752HCID 86689752, compound

Product 2

HCID 14923Ammonium HydroxideHCID 86689753HCID 86689753, compoundYield 78.3%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A stirred solution of 4-(6-tert-butylpyridin-2-ylamino)-6-chloropyridazine-3-carboxamide (317 mg, 1.04 mmol) and tert-butyl (1S,2R)-2-aminocyclohexylcarbamate (444 mg, 2.07 mmol) in NMP (4 mL) was heated at 140° C. for 24 h in a sealed tube. The mixture was concentrated in vacuo (Kuglerohr, high vacuum) to a brown solid. Purification by chromatography (silica, 40 g, 0-10% of a 9:1 MeOH solution in dichloromethane, 30 min) then a second purification by chromatography (silica, 24 g, 10% acetone in dichloromethane, 10 min, then 9:1:90 MeOH:NH4OH:DCM, 10 min) gave tert-butyl (1S,2R)-2-(5-(6-tert-butylpyridin-2-ylamino)-6-carbamoylpyridazin-3-ylamino)cyclohexylcarbamate (197 mg, 407 μmol, 39%) as a brown viscous gum. MS (EI/CI) m/z: 484.2 [M+H]. This material contained small amounts of residual NMP and was used directly in the next step without further purification.

Workup

  1. concentrationThe mixture was concentrated in vacuo (Kuglerohr, high vacuum) to a brown solid
  2. customPurification by chromatography (silica, 40 g, 0-10% of a 9:1 MeOH solution in dichloromethane, 30 min)
  3. customa second purification by chromatography (silica, 24 g, 10% acetone in dichloromethane, 10 min

Sources & evidence

ORD record
ord-6bd98dd621b7426e971d27b8e80ce361
Source dataset
uspto-grants-2014_12
Patent number
US08901124B2

Reaction notes

Loading…