Diisopropylethylamine → Methyl {[3-({[7-(3-{[(2-fluoro-5-methylphenyl)amino]carbonyl}phenoxy)thieno[3,2-b]pyridin-2-yl]carbonyl}amino)propyl]amino}acetate

HRID 525837Notes

Reaction equation

HRID 525837 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][C:3]=1[NH:9][C:10]([C:12]1[CH:13]=[C:14]([CH:28]=[CH:29][CH:30]=1)[O:15][C:16]1[CH:21]=[CH:20][N:19]=[C:18]2[CH:22]=[C:23]([C:25]([OH:27])=O)[S:24][C:17]=12)=[O:11].C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C.Cl.Cl.[NH2:75][CH2:76][CH2:77][CH2:78][NH:79][CH2:80][C:81]([O:83][CH3:84])=[O:82]>CN(C=O)C.O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][C:3]=1[NH:9][C:10]([C:12]1[CH:13]=[C:14]([CH:28]=[CH:29][CH:30]=1)[O:15][C:16]1[CH:21]=[CH:20][N:19]=[C:18]2[CH:22]=[C:23]([C:25]([NH:75][CH2:76][CH2:77][CH2:78][NH:79][CH2:80][C:81]([O:83][CH3:84])=[O:82])=[O:27])[S:24][C:17]=12)=[O:11]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 862904167-(3-{[(2-Fluoro-5-methylphenyl)amino]carbonyl}phenoxy)thieno[3,2-b]pyridine-2-carboxylic acidHCID 131735589Methyl [(3-aminopropyl)amino]acetate dihydrochloride

Product 1

HCID 86290461Methyl {[3-({[7-(3-{[(2-fluoro-5-methylphenyl)amino]carbonyl}phenoxy)thieno[3,2-b]pyridin-2-yl]carbonyl}amino)propyl]amino}acetate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred, cooled (0° C.) solution of 7-(3-{[(2-fluoro-5-methylphenyl)amino]carbonyl}phenoxy)thieno[3,2-b]pyridine-2-carboxylic acid (80 mg, 0.19 mmol) in anhydrous DMF (10 ml) were added PyBOP (109 mg, 0.21 mmol) and N,N-diisopropylethylamine (123 mg, 0.95 mmol). The mixture was stirred at 0° C. for 10 minutes, followed by addition of methyl [(3-aminopropyl)amino]acetate dihydrochloride (50 mg, 0.23 mmol). Stirring was continued at 0° C. for 10 minutes then room temperature for 2 hours. The mixture was poured into 100 ml of water with vigorous stirring. The precipitates were filtered, washed with water and dried to give the crude, which was purified by silica gel chromatography eluting with 5-8% methanol in chloroform to give methyl {[3-({[7-(3-{[(2-fluoro-5-methylphenyl)amino]carbonyl}phenoxy)thieno[3,2-b]pyridin-2-yl]carbonyl}amino)propyl]amino}acetate as light beige solid. Yield: 40 mg, 38%.

Workup

  1. stirringStirring
  2. waitwas continued at 0° C. for 10 minutes
  3. waitroom temperature for 2 hours
  4. filtrationThe precipitates were filtered
  5. washwashed with water
  6. customdried
  7. customto give the crude, which
  8. customwas purified by silica gel chromatography
  9. washeluting with 5-8% methanol in chloroform

Sources & evidence

ORD record
ord-aac89a72d9df44c0929bcd9b136c2262
Source dataset
uspto-grants-2016_05
Patent number
US09340555B2

Reaction notes

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