Dicyclohexylcarbodiimide → HCID 71007254, compound

HRID 716204Notes

Reaction equation

HRID 716204 reaction equation
[NH2:1][C@H:2]1[CH2:7][CH2:6][CH2:5][N:4]([C:8]2[CH:13]=[CH:12][N:11]=[CH:10][C:9]=2[NH:14][C:15]2[N:19]3[N:20]=[C:21]([C:24]4[C:29]([F:30])=[CH:28][CH:27]=[CH:26][N:25]=4)[CH:22]=[CH:23][C:18]3=[N:17][N:16]=2)[CH2:3]1.N(C1C=NC=CC=1N1CCC[C@H](N[C:47](=[O:53])[O:48][C:49]([CH3:52])([CH3:51])[CH3:50])C1)=C=S.FC1C(C2N=NC(NN)=CC=2)=NC=CC=1.C1CCC(N=C=NC2CCCCC2)CC1>C(#N)C>[F:30][C:29]1[C:24]([C:21]2[CH:22]=[CH:23][C:18]3[N:19]([C:15]([NH:14][C:9]4[CH:10]=[N:11][CH:12]=[CH:13][C:8]=4[N:4]4[CH2:5][CH2:6][CH2:7][C@H:2]([NH:1][C:47](=[O:53])[O:48][C:49]([CH3:52])([CH3:51])[CH3:50])[CH2:3]4)=[N:16][N:17]=3)[N:20]=2)=[N:25][CH:26]=[CH:27][CH:28]=1

Participants

6

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 70982426HCID 70982426, compoundHCID 71007279HCID 71007279, compoundHCID 131734124HCID 131734124, compound

Product 1

HCID 71007254HCID 71007254, compoundYield 90%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
85 °C

Procedure

N-(4-((3S)-3-amino-1-piperidinyl)-3-pyridinyl)-6-(3-fluoro-2-pyridinyl)[1,2,4]triazolo[4,3-b]pyridazin-3-amine. A mixture of (S)-tert-butyl (1-(3-isothiocyanatopyridin-4-yl)piperidin-3-yl)carbamate (193 mg, 0.58 mmol, Preparation XI) and 3-(3-fluoropyridin-2-yl)-6-hydrazinylpyridazine (113 mg, 0.551 mmol) in ACN (2 mL) was heated at 85° C. for 30 min. After the reaction mixture was cooled to RT, it was treated with DCC (125 mg, 0.60 mmol) and heating was resumed at 90° C. for 2 h. The reaction mixture was concentrated under reduced pressure. The residue was purified by silica gel chromatography (50-100% EtOAc in DCM followed by 1-10% MeOH in EtOAc) to provide (S)-tert-butyl (1-(3-((6-(3-fluoropyridin-2-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)amino)pyridin-4-yl)piperidin-3-yl)carbamate (250 mg, 90% yield) as a dark green crystalline solid. MS (ESI, pos. ion) m/z: 506.0 (M+1).

Workup

  1. temperatureAfter the reaction mixture was cooled to RT
  2. temperatureheating
  3. concentrationThe reaction mixture was concentrated under reduced pressure
  4. customThe residue was purified by silica gel chromatography (50-100% EtOAc in DCM followed by 1-10% MeOH in EtOAc)

Sources & evidence

ORD record
ord-12a27854e21e43ebbf56053c5ead7e85
Source dataset
uspto-grants-2015_11
Patent number
US09187486B2

Reaction notes

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