1,1'-Carbonyldiimidazole → HCID 136009246, compound

HRID 1969665Notes

Reaction equation

HRID 1969665 reaction equation
[CH2:1]([C@H:3]1[CH2:7][NH:6][CH2:5][C@H:4]1[C:8]1[N:12]2[C:13]3[CH:19]=[CH:18][N:17](S(C4C=CC(C)=CC=4)(=O)=O)[C:14]=3[N:15]=[CH:16][C:11]2=[N:10][N:9]=1)[CH3:2].Cl.CCN(C(C)C)C(C)C.C1N=CN([C:45]([N:47]2C=N[CH:49]=[CH:48]2)=[O:46])C=1.NCC1[CH2:59][CH2:58][O:57][CH2:56][CH2:55]1>C1COCC1.CN(C1C=CN=CC=1)C>[CH2:1]([C@H:3]1[C@@H:4]([C:8]2[N:12]3[C:13]4[CH:19]=[CH:18][NH:17][C:14]=4[N:15]=[CH:16][C:11]3=[N:10][N:9]=2)[CH2:5][N:6]([C:45]([NH:47][CH2:48][CH:49]2[CH2:59][CH2:58][O:57][CH2:56][CH2:55]2)=[O:46])[CH2:7]1)[CH3:2]

Participants

7

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 81531DiisopropylethylamineHCID 27732104-Aminomethyltetrahydropyran2×HCID 67998177HCID 67998177, compound

Product 1

HCID 136009246HCID 136009246, compoundYield 10.5%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1-((cis)-4-ethylpyrrolidin-3-yl)-6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazine•hydrochloride (0.075 g, 0.168 mmol, Example #36, step F) in THF (1.00 mL) was added DIEA (0.150 mL, 0.861 mmol) and CDI (0.027 g, 0.168 mmol). After about 1 h, 4-aminomethyltetrahydropyran (0.020 g, 0.17 mmol, Acros) was added and the reaction mixture was stirred at ambient temperature for about 16 h. The reaction mixture was heated at about 55° C. for about 24 h. DMAP (0.021 g, 0.168 mmol) was added and continued stirring at about 55° C. for about 48 h. 4-aminomethyltetrahydropyran (0.400 g, 3.47 mmol, Acros) was added and continued stirring at about 55° C. for about 24 h. The solvent was removed under reduced pressure. The crude material was purified by RP-HPLC (Table 1, Method m) to afford (cis)-3-ethyl-4-(6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)-N-((tetrahydro-2H-pyran-4-yl)methyl)pyrrolidine-1-carboxamide (0.007 g, 10%) as product: LC/MS (Table 1, Method a) Rt=1.32 min; MS m/z: 398 (M+H)+.

Workup

  1. temperatureThe reaction mixture was heated at about 55° C. for about 24 h
  2. stirringcontinued stirring at about 55° C. for about 48 h
  3. stirringcontinued stirring at about 55° C. for about 24 h
  4. customThe solvent was removed under reduced pressure
  5. customThe crude material was purified by RP-HPLC (Table 1, Method m)

Sources & evidence

ORD record
ord-a64094dc108749fbadcf028ae4cb8c1a
Source dataset
uspto-grants-2013_04
Patent number
US08426411B2

Reaction notes

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