(1S,2R)-Cyclohexane-1,2-diamine, N1-BOC protected → HCID 86689759, compound

HRID 1396407Notes

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[C:20]3[N:19]=[CH:18][N:17]([CH3:21])[C:16]=3[CH:15]=[CH:14][CH: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]>CN1CCCC1=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[C:20]2[N:19]=[CH:18][N:17]([CH3:21])[C:16]=2[CH:15]=[CH:14][CH:13]=1)(=[O:9])[NH2:10]

Participants

Conditions

Temperature: 120 °C

Procedure

A solution of 6-chloro-4-(1-methyl-1H-benzo[d]imidazol-4-ylamino)pyridazine-3-carboxamide (260 mg, 859 μmol) in N-methyl-2-pyrrolidinone (3.0 mL) was treated with tert-butyl (1S,2R)-2-aminocyclohexylcarbamate (368 mg, 1.72 mmol), and the mixture was heated to 120° C. for 72 h. The solvent was evaporated under high vacuum and the residue was purified by chromatography (spherical silica 20-45 μM, 80 g, Versaflash Supelco, 0 to 5% of a 9:1 MeOH: NH4OH solution in CH2Cl2, 20 min) to give tert-butyl (1S,2R)-2-(6-carbamoyl-5-(1-methyl-1H-benzo[d]imidazol-4-ylamino)pyridazin-3-ylamino)cyclohexylcarbamate (132 mg, 32%) as a light brown foam. 1H NMR (CHLOROFORM-d) δ: 11.05 (s, 1H), 7.89 (d, J=2.6 Hz, 1H), 7.77 (s, 1H), 7.39 (br. s., 1H), 6.96-7.30 (m, 3H), 6.40 (br. s., 1H), 6.10-6.33 (m, 2H), 3.78 (br. s., 4H), 3.52 (br. s., 1H), 0.95-1.70 (m, 17H); LC-MS 481.0 [M+H]+.

Workup

customThe solvent was evaporated under high vacuum
customthe residue was purified by chromatography (spherical silica 20-45 μM, 80 g, Versaflash Supelco, 0 to 5% of a 9:1 MeOH: NH4OH solution in CH2Cl2, 20 min)

Sources & evidence

ORD record: ord-877f9fd35f2d4ec09fb916f0ed0687ed
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08901124B2

Reaction notes

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