Trifluoroacetic acid → 4-(6-(1H-pyrazol-1-yl)pyridin-2-ylamino)-6-((1R,2S)-2-aminocyclohexylamino)pyridazine-3-carboxamide

HRID 1396448Notes

Reaction equation

HRID 1396448 reaction equation
[N:1]1([C:6]2[N:11]=[C:10]([NH:12][C:13]3[CH:14]=[C:15]([NH:22][C@@H:23]4[CH2:28][CH2:27][CH2:26][CH2:25][C@@H:24]4[NH:29]C(=O)OC(C)(C)C)[N:16]=[N:17][C:18]=3[C:19](=[O:21])[NH2:20])[CH:9]=[CH:8][CH:7]=2)[CH:5]=[CH:4][CH:3]=[N:2]1.FC(F)(F)C(O)=O>ClCCl>[N:1]1([C:6]2[N:11]=[C:10]([NH:12][C:13]3[CH:14]=[C:15]([NH:22][C@@H:23]4[CH2:28][CH2:27][CH2:26][CH2:25][C@@H:24]4[NH2:29])[N:16]=[N:17][C:18]=3[C:19]([NH2:20])=[O:21])[CH:9]=[CH:8][CH:7]=2)[CH:5]=[CH:4][CH:3]=[N:2]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86689788tert-butyl (1S,2R)-2-(5-(6-(1H-pyrazol-1-yl)pyridin-2-ylamino)-6-carbamoylpyridazin-3-ylamino)cyclohexylcarbamate

Product 1

HCID 716260424-(6-(1H-pyrazol-1-yl)pyridin-2-ylamino)-6-((1R,2S)-2-aminocyclohexylamino)pyridazine-3-carboxamideYield 25.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl (1S,2R)-2-(5-(6-(1H-pyrazol-1-yl)pyridin-2-ylamino)-6-carbamoylpyridazin-3-ylamino)cyclohexylcarbamate (70 mg, 142 μmol) in dichloromethane (2.5 mL) was added trifluoroacetic acid (2.01 g, 1.35 mL, 17.6 mmol) and the mixture stirred at 25° for 2 h. The mixture was concentrated in vacuo and then diluted with dichloromethane and then washed successively with 1N NaOH (3×5 mL) and brine (5 mL). The organic phase was dried over sodium sulfate, concentrated in vacuo and then dried in vacuo to give 4-(6-(1H-pyrazol-1-yl)pyridin-2-ylamino)-6-((1R,2S)-2-aminocyclohexylamino)pyridazine-3-carboxamide (14.2 mg, 36.1 μmol, 25%) as a white solid. 1H NMR (DMSO-d6) δ: 11.93 (s, 1H), 8.63-8.71 (m, 1H), 8.45 (br. s., 1H), 7.78-7.94 (m, 3H), 7.71 (br. s., 1H), 7.51 (d, J=7.8 Hz, 1H), 7.05 (d, J=7.5 Hz, 1H), 6.92 (d, J=8.0 Hz, 1H), 6.63 (dd, J=2.5, 1.8 Hz, 1H), 4.02 (br. s., 1H), 3.18 (br. s., 1H), 1.46-1.79 (m, 7H), 1.20-1.41 (m, 3H); MS (EI/CI) m/z: 394.3 [M+H].

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. additiondiluted with dichloromethane
  3. washwashed successively with 1N NaOH (3×5 mL) and brine (5 mL)
  4. dry with materialThe organic phase was dried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customdried in vacuo

Sources & evidence

ORD record
ord-63d85a71189d4c30b57c1d1ce7656b4f
Source dataset
uspto-grants-2014_12
Patent number
US08901124B2

Reaction notes

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