1-Hydroxybenzotriazole → HCID 57686321, compound

HRID 1038034Notes

Reaction equation

HRID 1038034 reaction equation
[CH3:1][NH:2][C:3]([C:5]1[C:13]2[C:8](=[CH:9][CH:10]=[C:11]([NH:14][C:15]([CH:17]3[CH2:21][CH2:20][N:19]([CH2:22][C:23]([OH:25])=O)[CH2:18]3)=[O:16])[CH:12]=2)[NH:7][N:6]=1)=[O:4].CNC(C1C2C(=CC=C(N)C=2)NN=1)=O.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.[N:62]1([C:68]2[S:69][C:70]([C:73]3[N:78]=[CH:77][CH:76]=[CH:75][N:74]=3)=[CH:71][N:72]=2)[CH2:67][CH2:66][NH:65][CH2:64][CH2:63]1.CCN(C(C)C)C(C)C>CN(C=O)C.O.C(OCC)(=O)C>[CH3:1][NH:2][C:3]([C:5]1[C:13]2[C:8](=[CH:9][CH:10]=[C:11]([NH:14][C:15]([CH:17]3[CH2:21][CH2:20][N:19]([CH2:22][C:23](=[O:25])[N:65]4[CH2:66][CH2:67][N:62]([C:68]5[S:69][C:70]([C:73]6[N:78]=[CH:77][CH:76]=[CH:75][N:74]=6)=[CH:71][N:72]=5)[CH2:63][CH2:64]4)[CH2:18]3)=[O:16])[CH:12]=2)[NH:7][N:6]=1)=[O:4]

Participants

10

Reactant 6

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 225673195-Amino-N-methyl-1H-indazole-3-carboxamideHCID 57685850[3-(3-methylcarbamoyl-1H-indazol-5-ylcarbamoyl)-pyrrolidin-1-yl]-acetic acidHCID 59511374HCID 59511374, compound

Product 1

HCID 57686321HCID 57686321, compoundYield 38%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of [3-(3-methylcarbamoyl-1H-indazol-5-ylcarbamoyl)-pyrrolidin-1-yl]-acetic acid (15 mg, 0.043 mmol, prepared by a procedure similar to that of Example 98 using the indazole of Example 85 instead of indazole 65) and HOBt (7 mg, 0.052 mmol) in DMF (0.5 mL) at 0° C., EDCl (10 mg, 0.052 mmol) was added and the resulted reaction mixture was stirred at this temperature for 0.5 hour. To this solution was added 2-(2-piperazin-1-yl-thiazol-5-yl)-pyrimidine (18 mg, 0.052 mmol) made from previous step, followed by DIEA (7 μL). The reaction was stirred at 0° C. for 1 hour and was gradually warm up to room temperature and was continuously stirred for overnight. Ethyl acetate (5 mL) was then added, followed by water (10 mL). The organic layer was collected, dry over sodium sulfate, evaporate of solvent and residue was purified using prep-HPLC. To the solution obtained from HPCL, HCl (1N, 2 mL) was added and the solution was brought to dryness under vacuum. The formed residue was then dissolved in acetonitrile/water (3:1) and was lyophilized to give desired product (10 mg, 38% yield) as hydrochloride salt.

Workup

  1. customthe resulted reaction mixture
  2. stirringThe reaction was stirred at 0° C. for 1 hour
  3. stirringwas continuously stirred for overnight
  4. customThe organic layer was collected
  5. dry with materialdry over sodium sulfate
  6. customevaporate of solvent and residue
  7. customwas purified
  8. additionwas added
  9. dissolutionThe formed residue was then dissolved in acetonitrile/water (3:1)

Sources & evidence

ORD record
ord-30416b2f01fc4772ab4d695c2ac25257
Source dataset
uspto-grants-2013_10
Patent number
US08546404B2

Reaction notes

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