Trifluoroacetic acid → 6-((3R,4R)-3-aminotetrahydro-2H-pyran-4-ylamino)-4-(5-fluoro-6-isopropylpyridin-2-ylamino)pyridazine-3-carboxamide

HRID 1396484Notes

Reaction equation

HRID 1396484 reaction equation
[C:1]([C:4]1[N:9]=[N:8][C:7]([NH:10][C@@H:11]2[CH2:16][CH2:15][O:14][CH2:13][C@@H:12]2[NH:17]C(=O)OC(C)(C)C)=[CH:6][C:5]=1[NH:25][C:26]1[CH:31]=[CH:30][C:29]([F:32])=[C:28]([CH:33]([CH3:35])[CH3:34])[N:27]=1)(=[O:3])[NH2:2].FC(F)(F)C(O)=O>ClCCl.[NH4+].[OH-].O>[NH2:17][C@@H:12]1[C@H:11]([NH:10][C:7]2[N:8]=[N:9][C:4]([C:1]([NH2:2])=[O:3])=[C:5]([NH:25][C:26]3[CH:31]=[CH:30][C:29]([F:32])=[C:28]([CH:33]([CH3:35])[CH3:34])[N:27]=3)[CH:6]=2)[CH2:16][CH2:15][O:14][CH2:13]1

Participants

6

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86689809tert-butyl (3R,4R)-4-(6-carbamoyl-5-(5-fluoro-6-isopropylpyridin-2-ylamino)pyridazin-3-ylamino)tetrahydro-2H-pyran-3-ylcarbamate

Product 1

HCID 716261026-((3R,4R)-3-aminotetrahydro-2H-pyran-4-ylamino)-4-(5-fluoro-6-isopropylpyridin-2-ylamino)pyridazine-3-carboxamideYield 49%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×HCID 14923Ammonium HydroxideSolvent

Procedure

To a solution of tert-butyl (3R,4R)-4-(6-carbamoyl-5-(5-fluoro-6-isopropylpyridin-2-ylamino)pyridazin-3-ylamino)tetrahydro-2H-pyran-3-ylcarbamate (100 mg, 204 μmol) in dichloromethane (3 mL) was added trifluoroacetic acid (466 mg, 315 μL, 4.1 mmol) and the mixture stirred at room temperature for 16 h. The mixture was diluted with 25% aqueous NH4OH, dichloromethane, and water. The organic phase was separated and washed with water (2×), then concentrated in vacuo and purified by chromatography (silica, 3 to 10% methanol in dichloromethane) to give 6-((3R,4R)-3-aminotetrahydro-2H-pyran-4-ylamino)-4-(5-fluoro-6-isopropylpyridin-2-ylamino)pyridazine-3-carboxamide (39 mg, 100 μmol, 49%) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.76 (s, 1H), 8.39 (s, 1H), 7.85 (s, 1H), 7.65 (s, 1H), 7.60 (t, J=9.2 Hz, 1H), 6.88 (dd, J=8.9, 2.9 Hz, 1H), 6.78 (d, J=7.7 Hz, 1H), 3.96 (br. s, 1H), 3.80 (m, 1H), 3.70 (dd, J=11.4, 2.8 Hz, 1H), 3.49 (dd, J=11.4. 1.7 Hz, 1H), 3.37 (m, 2H), 2.96 (s, 1H), 1.80 (m, 1H), 1.69 (m, 2H), 1.29 (d, J=6.8 Hz, 6H); MS (EI/CI) m/z: 390.2 [M+H].

Workup

  1. customThe organic phase was separated
  2. washwashed with water (2×)
  3. concentrationconcentrated in vacuo
  4. custompurified by chromatography (silica, 3 to 10% methanol in dichloromethane)

Sources & evidence

ORD record
ord-9cb493ab98f4408c8c809ca1796ea53b
Source dataset
uspto-grants-2014_12
Patent number
US08901124B2

Reaction notes

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