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(1S,2R)-Cyclohexane-1,2-diamine, N1-BOC protected → tert-butyl (1S,2R)-2-(6-carbamoyl-5-(4-methyl-6-propylpyridin-2-ylamino)pyridazin-3-ylamino)cyclohexylcarbamate

HRID 1396471
Notes
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Reaction equation

HRID 1396471 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]=[C:16]([CH3:18])[CH:15]=[C:14]([CH2:19][CH2:20][CH3:21])[N:13]=2)[CH:3]=1.[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]>CN1C(=O)CCC1.C(OCC)(=O)C.[Cl-].[Na+].O>[C:8]([C:5]1[N:6]=[N:7][C:2]([NH:22][C@@H:23]2[CH2:28][CH2:27][CH2:26][CH2:25][C@@H:24]2[NH:29][C:30](=[O:36])[O:31][C:32]([CH3:34])([CH3:33])[CH3:35])=[CH:3][C:4]=1[NH:11][C:12]1[CH:17]=[C:16]([CH3:18])[CH:15]=[C:14]([CH2:19][CH2:20][CH3:21])[N:13]=1)(=[O:9])[NH2:10]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 2

HCID 1514389(1S,2R)-Cyclohexane-1,2-diamine, N1-BOC protectedHCID 86689801HCID 86689801, compound

Product 1

HCID 86689802tert-butyl (1S,2R)-2-(6-carbamoyl-5-(4-methyl-6-propylpyridin-2-ylamino)pyridazin-3-ylamino)cyclohexylcarbamateYield 43%

Reagents, catalysts & solvents 3

HCID 8857Ethyl AcetateSolvent
HCID 13387
N-methyl-2-pyrrolidone
Solvent
HCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
140 °C

Procedure

To a solution of 6-chloro-4-(4-methyl-6-propylpyridin-2-ylamino)pyridazine-3-carboxamide (134 mg, 438 μmol) in NMP (1.5 mL) was added tert-butyl (1S,2R)-2-aminocyclohexylcarbamate (376 mg, 1.75 mmol) in 3 portions approximately every 12 h over 36 h, with heating at 140° C. in the periods between additions. The mixture was then diluted with ethyl acetate and brine. The phases were separated and the organic phase washed twice with brine. The organic phase was concentrated in vacuo and then purified by chromatography (silica, 30 to 100% ethyl acetate in hexanes) to give tert-butyl (1S,2R)-2-(6-carbamoyl-5-(4-methyl-6-propylpyridin-2-ylamino)pyridazin-3-ylamino)cyclohexylcarbamate (91 mg, 188 μmol, 43%) as a light brown solid. MS (EI/CI) m/z: 484.3 [M+H].

Workup

  1. customThe phases were separated
  2. washthe organic phase washed twice with brine
  3. concentrationThe organic phase was concentrated in vacuo
  4. custompurified by chromatography (silica, 30 to 100% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-bbdd78dab214401288725c23e95f38ee
Source dataset
uspto-grants-2014_12
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08901124B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes