(1S,2R)-Cyclohexane-1,2-diamine, N1-BOC protected → tert-Butyl (1S,2R)-2-(6-carbamoyl-5-(6-propylpyridin-2-ylamino)pyridazin-3-ylamino)cyclohexylcarbamate
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][CH:15]=[C:14]([CH2:18][CH2:19][CH3:20])[N:13]=2)[CH:3]=1.[NH2:21][C@@H:22]1[CH2:27][CH2:26][CH2:25][CH2:24][C@@H:23]1[NH:28][C:29](=[O:35])[O:30][C:31]([CH3:34])([CH3:33])[CH3:32]>CN1CCCC1=O>[C:8]([C:5]1[N:6]=[N:7][C:2]([NH:21][C@@H:22]2[CH2:27][CH2:26][CH2:25][CH2:24][C@@H:23]2[NH:28][C:29](=[O:35])[O:30][C:31]([CH3:33])([CH3:32])[CH3:34])=[CH:3][C:4]=1[NH:11][C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([CH2:18][CH2:19][CH3:20])[N:13]=1)(=[O:9])[NH2:10]Participants
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 130 °C
Procedure
6-Chloro-4-(6-propylpyridin-2-ylamino)pyridazine-3-carboxamide (289 mg, 991 μmol) and tert-butyl (1S,2R)-2-aminocyclohexylcarbamate (425 mg, 1.98 mmol) were dissolved in N-methyl-2-pyrrolidinone (2 mL) and heated at 130° C. for 24 h. LCMS showed desired product mass, as well as starting material. A third equivalent of tert-butyl (1S,2R)-2-aminocyclohexylcarbamate was added (213 mg, 0.991 mmol) and heating continued. After 8 h, a third portion of tert-butyl (1S,2R)-2-aminocyclohexylcarbamate (0.310 g) was added. After 24 h, the mixture was cooled and concentrated in vacuo (high vacuum, 100° C.) to a brown solid residue. Purification by chromatography (silica, 0 to 10% of a 9:1 MeOH:NH4OH solution in dichloromethane, 20 min) gave tert-butyl (1S,2R)-2-(6-carbamoyl-5-(6-propylpyridin-2-ylamino)pyridazin-3-ylamino)cyclohexylcarbamate (271 mg, 577 μmol, 58%) as a light brown solid. LC-MS 470.2 [M+H]+.
Sources & evidence
- ORD record
- ord-47312103054c42068a7d86afd80eeaec
- Source dataset
- uspto-grants-2014_12
- Patent number
- US08901124B2
Reaction notes
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