Ethanol → HCID 71626969, compound

HRID 1396399Notes

Reaction equation

HRID 1396399 reaction equation
[C:1]([C:5]1[N:10]=[C:9]([NH:11][C:12]2[CH:13]=[C:14]([NH:21][C@@H:22]3[CH2:27][CH2:26][CH2:25][CH2:24][C@@H:23]3[NH:28]C(=O)OC(C)(C)C)[N:15]=[N:16][C:17]=2[C:18](=[O:20])[NH2:19])[CH:8]=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].C(O)(C(F)(F)F)=O.C(O)C>ClCCl>[NH2:28][C@H:23]1[CH2:24][CH2:25][CH2:26][CH2:27][C@H:22]1[NH:21][C:14]1[N:15]=[N:16][C:17]([C:18]([NH2:19])=[O:20])=[C:12]([NH:11][C:9]2[CH:8]=[CH:7][CH:6]=[C:5]([C:1]([CH3:4])([CH3:3])[CH3:2])[N:10]=2)[CH:13]=1

Participants

5

Reactant 3

HCID 702EthanolHCID 6422Trifluoroacetic acidHCID 86689753HCID 86689753, compound

Product 1

HCID 71626969HCID 71626969, compoundYield 37.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl (1S,2R)-2-(5-(6-tert-butylpyridin-2-ylamino)-6-carbamoylpyridazin-3-ylamino)cyclohexylcarbamate (192 mg, 397 μmol) in dichloromethane (2 mL) was added TFA (747 mg, 505 μL, 6.55 mmol). After 14 h, the mixture was concentrated in vacuo then purified by chromatography (spherical silica, 50 g, 0-20% of a 9:1 MeOH:NH4OH solution in dichloromethane, 30 min) to give a pale brown gum. This was triturated with ethanol and concentrated to give a yellow solid. Trituration again with hot ethanol, followed by decanting of the supernatant, gave 6-((1R,2S)-2-aminocyclohexylamino)-4-(6-tert-butylpyridin-2-ylamino)pyridazine-3-carboxamide (57 mg, 149 μmol, 37%) as a cream powder after drying under high vacuum. 1H NMR (DMSO-d6) δ: 11.80 (s, 1H), 8.39 (d, J=2.0 Hz, 1H), 7.98 (s, 1H), 7.55-7.76 (m, 2H), 6.96-7.09 (m, 1H), 6.77 (dd, J=8.1, 0.5 Hz, 1H), 6.70 (d, J=8.1 Hz, 1H), 3.67 (br. s., 1H), 3.03-3.12 (m, 1H), 1.45-1.72 (m, 8H), 1.22-1.41 (m, 11H); MS (EI/CI) m/z: 384.2 [M+H].

Workup

  1. concentrationthe mixture was concentrated in vacuo
  2. customthen purified by chromatography (spherical silica, 50 g, 0-20% of a 9:1 MeOH:NH4OH solution in dichloromethane, 30 min)
  3. customto give a pale brown gum
  4. customThis was triturated with ethanol
  5. concentrationconcentrated
  6. customto give a yellow solid
  7. customby decanting of the supernatant

Sources & evidence

ORD record
ord-13604f211919457bba84fe9e65c5cab3
Source dataset
uspto-grants-2014_12
Patent number
US08901124B2

Reaction notes

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