1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 68513136, compound

HRID 2241338Notes

Reaction equation

HRID 2241338 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(C)C)C(C)C.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.O.[CH3:49][O:50][C:51]1[CH:83]=[CH:82][C:54]([CH2:55][N:56]2[C:60]3=[N:61][CH:62]=[CH:63][C:64]([O:65][C:66]4[CH:71]=[CH:70][C:69]([NH2:72])=[CH:68][C:67]=4[F:73])=[C:59]3[C:58]([N:74]3[CH2:78][CH2:77][C@H:76]([N:79]([CH3:81])[CH3:80])[CH2:75]3)=[N:57]2)=[CH:53][CH:52]=1>ClCCl>[CH3:80][N:79]([CH3:81])[C@H:76]1[CH2:77][CH2:78][N:74]([C:58]2[C:59]3[C:60](=[N:61][CH:62]=[CH:63][C:64]=3[O:65][C:66]3[CH:71]=[CH:70][C:69]([NH:72][C:15]([C:12]4[C:13](=[O:14])[N:8]([C:5]5[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=5)[N:9]=[CH:10][CH:11]=4)=[O:17])=[CH:68][C:67]=3[F:73])[N:56]([CH2:55][C:54]3[CH:82]=[CH:83][C:51]([O:50][CH3:49])=[CH:52][CH:53]=3)[N:57]=2)[CH2:75]1

Participants

7

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81531DiisopropylethylamineHCID 27960291-Hydroxybenzotriazole hydrateHCID 667671712-(4-Fluorophenyl)-3-oxo-2,3-dihydropyridazine-4-carboxylic acidHCID 68513147HCID 68513147, compound

Product 1

HCID 68513136HCID 68513136, compoundYield 101.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

To a stirred suspension of 2-(4-fluorophenyl)-3-oxo-2,3-dihydropyridazine-4-carboxylic acid (prepared in Example 19, step C) (7 mg, 0.03 mmol) in 300 μL dichloromethane at room temperature under nitrogen was added DIEA (10 μL, 0.06 mmol) followed by EDCI (5.7 mg, 0.03 mmol) and HOBT-H2O (4.6 mg, 0.03 mmol). After stirring for 10 minutes, a solution of (S)-1-(1-(4-methoxybenzyl)-4-(4-amino-2-fluorophenoxy)-1H-pyrazolo[3,4-b]pyridin-3-yl)-N,N-dimethylpyrrolidin-3-amine (9.5 mg, 0.02 mmol) in 300 μL dichloromethane was added. After stirring overnight, the reaction was diluted to 30 mL with CH2Cl2 and washed with 10% sodium carbonate solution. The organic layers were dried (MgSO4), filtered and concentrated. The crude product was loaded onto a Biotage 12S column with dichloromethane and eluted with a step gradient of dichloromethane (150 mL), 2.5/97.5 MeOH/dichloromethane (150 mL) and 5/95 MeOH/dichloromethane (200 mL) to afford the desired product as a tan oil (14 mg, 100%).

Workup

  1. stirringAfter stirring overnight
  2. washwashed with 10% sodium carbonate solution
  3. dry with materialThe organic layers were dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. washeluted with a step gradient of dichloromethane (150 mL), 2.5/97.5 MeOH/dichloromethane (150 mL) and 5/95 MeOH/dichloromethane (200 mL)

Sources & evidence

ORD record
ord-d500b6b4103148a68dc8796b7a7c6353
Source dataset
uspto-grants-2010_05
Patent number
US07723330B2

Reaction notes

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