1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 68516932, compound

HRID 2241391Notes

Reaction equation

HRID 2241391 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:13](=[O:14])[C:12]([C:15]([OH:17])=O)=[CH:11][CH:10]=[N:9]2)=[CH:4][CH:3]=1.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.[CH3:39][O:40][C:41]1[CH:83]=[CH:82][C:44]([CH2:45][N:46]2[C:50]3=[N:51][CH:52]=[CH:53][C:54]([O:55][C:56]4[CH:61]=[CH:60][C:59]([NH2:62])=[CH:58][C:57]=4[F:63])=[C:49]3[C:48]([C:64]3[CH:65]=[N:66][N:67]([CH:69]4[CH2:74][CH2:73][N:72]([C:75]([O:77][C:78]([CH3:81])([CH3:80])[CH3:79])=[O:76])[CH2:71][CH2:70]4)[CH:68]=3)=[N:47]2)=[CH:43][CH:42]=1.CCN(C(C)C)C(C)C>O.CN(C=O)C>[F:63][C:57]1[CH:58]=[C:59]([NH:62][C:15]([C:12]2[C:13](=[O:14])[N:8]([C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=3)[N:9]=[CH:10][CH:11]=2)=[O:17])[CH:60]=[CH:61][C:56]=1[O:55][C:54]1[CH:53]=[CH:52][N:51]=[C:50]2[N:46]([CH2:45][C:44]3[CH:43]=[CH:42][C:41]([O:40][CH3:39])=[CH:83][CH:82]=3)[N:47]=[C:48]([C:64]3[CH:65]=[N:66][N:67]([CH:69]4[CH2:74][CH2:73][N:72]([C:75]([O:77][C:78]([CH3:80])([CH3:81])[CH3:79])=[O:76])[CH2:71][CH2:70]4)[CH:68]=3)[C:49]=12

Participants

8

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 667671712-(4-Fluorophenyl)-3-oxo-2,3-dihydropyridazine-4-carboxylic acidHCID 68514117HCID 68514117, compound

Product 1

HCID 68516932HCID 68516932, compoundYield 5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

A 25 mL round-bottomed flask was charged with 2-(4-fluorophenyl)-3-oxo-2,3-dihydropyridazine-4-carboxylic acid (0.0840 g, 0.358 mmol obtained from Example 19, step C), EDCI (0.0687 g, 0.358 mmol), HOBT (0.0549 g, 0.358 mmol), and DMF (5 mL). The reaction mixture was stirred for 30 minute and tert-butyl 4-(4-(1-(4-methoxybenzyl)-4-(4-amino-2-fluorophenoxy)-1H-pyrazolo[3,4-b]pyridin-3-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate (0.110 g, 0.179 mmol) and Hunig's base (0.0463 g, 0.358 mmol) were added. The reaction mixture was stirred for 18 hours, then diluted with water and extracted with EtOAc. The organic layer was dried over sodium sulfate, filtered and concentrated. The crude material was purified by preparative TLC (0.5 mm thickness) eluting with CHCl3/MeOH(NH3 7N) 4:1. To the isolated product was added TFA (2 mL) and the solution was heated to 70° C. for 1 hour. The solution was concentrated and triturated with DCM/MeOH 1:1. The solids were collected by filtration to provide 5.1 mg (5%) of the desired product. LRMS M+1 (610.0) observed.

Workup

  1. stirringThe reaction mixture was stirred for 18 hours
  2. extractionextracted with EtOAc
  3. dry with materialThe organic layer was dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude material was purified by preparative TLC (0.5 mm thickness)
  7. washeluting with CHCl3/MeOH(NH3 7N) 4:1
  8. additionTo the isolated product was added TFA (2 mL)
  9. concentrationThe solution was concentrated
  10. customtriturated with DCM/MeOH 1:1
  11. filtrationThe solids were collected by filtration

Sources & evidence

ORD record
ord-b88736b6616641e5813d56c6c2dfcd7a
Source dataset
uspto-grants-2010_05
Patent number
US07723330B2

Reaction notes

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