(3-Methoxyphenyl)acetic acid → 3-(1-{[3-(methyloxy)phenyl]acetyl}-2,3-dihydro-1H-indol-5-yl)thieno[3,2-c]pyridin-4-amine

HRID 1909946Notes

Reaction equation

HRID 1909946 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][C:6]([C:10]3[C:14]4[C:15]([NH2:19])=[N:16][CH:17]=[CH:18][C:13]=4[S:12][CH:11]=3)=[CH:7][CH:8]=2)[CH2:3][CH2:2]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:44][O:45][C:46]1[CH:47]=[C:48]([CH2:52][C:53](O)=[O:54])[CH:49]=[CH:50][CH:51]=1.CCN(C(C)C)C(C)C>O.CN(C)C=O>[CH3:44][O:45][C:46]1[CH:47]=[C:48]([CH2:52][C:53]([N:1]2[C:9]3[C:4](=[CH:5][C:6]([C:10]4[C:14]5[C:15]([NH2:19])=[N:16][CH:17]=[CH:18][C:13]=5[S:12][CH:11]=4)=[CH:7][CH:8]=3)[CH2:3][CH2:2]2)=[O:54])[CH:49]=[CH:50][CH:51]=1

Participants

7

Reactant 4

HCID 15719(3-Methoxyphenyl)acetic acidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 668235693-(2,3-dihydro-1H-indol-5-yl)thieno[3,2-c]pyridin-4-amine

Product 1

HCID 534671733-(1-{[3-(methyloxy)phenyl]acetyl}-2,3-dihydro-1H-indol-5-yl)thieno[3,2-c]pyridin-4-amineYield 44.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a 4 mL screw cap vial was added 3-(2,3-dihydro-1H-indol-5-yl)thieno[3,2-c]pyridin-4-amine (100 mg, 0.374 mmol) followed by HATU (142 mg, 0.374 mmol), 3-methoxyphenylacetic acid (62.2 mg, 0.374 mmol) and DIEA (0.261 mL, 1.496 mmol). N,N-Dimethylformamide (DMF) (2 mL) was added and the reaction was sealed and left to stir at room temperature overnight. The reaction mixture was poured into water (4 mL) and extracted with EtOAc (5 mL). The organics were dried over Na2SO4 and concentrated. The residue was taken up in DCM and purified via normal phase chromatography (0-10% MeOH/DCM). Fractions were collected and concentrated to afford 3-(1-{[3-(methyloxy)phenyl]acetyl}-2,3-dihydro-1H-indol-5-yl)thieno[3,2-c]pyridin-4-amine (69.4 mg) as a white solid. LC/MS (ES) m/z=416.2 [M+H]+ 1H NMR (400 MHz, DMSO-d6) δ ppm 3.22 (t, J=8.34 Hz, 2H) 3.75 (s, 3H) 3.86 (s, 2H) 4.23 (t, J=8.46 Hz, 2H) 5.54 (br. s., 2H) 6.84 (dd, J=8.21, 2.40 Hz, 1H) 6.87-6.91 (m, 2H) 7.21-7.27 (m, 2H) 7.29 (d, J=5.56 Hz, 1H) 7.33 (s, 1H) 7.44 (s, 1H) 7.83 (d, J=5.81 Hz, 1H) 8.17 (d, J=8.34 Hz, 1H).

Workup

  1. customTo a 4 mL screw cap
  2. customthe reaction was sealed
  3. waitleft
  4. extractionextracted with EtOAc (5 mL)
  5. dry with materialThe organics were dried over Na2SO4
  6. concentrationconcentrated
  7. custompurified via normal phase chromatography (0-10% MeOH/DCM)
  8. customFractions were collected
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-07fc8478fc0b4bfeb9b5716026d5a3ec
Source dataset
uspto-grants-2013_12
Patent number
US08598156B2

Reaction notes

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