Diisopropylethylamine → 3-{2-[5-(4-aminothieno[3,2-c]pyridin-3-yl)-2,3-dihydro-1H-indol-1-yl]-2-oxoethyl}benzonitrile

HRID 1909964Notes

Reaction equation

HRID 1909964 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.[C:44]([C:46]1[CH:47]=[C:48]([CH2:52][C:53](O)=[O:54])[CH:49]=[CH:50][CH:51]=1)#[N:45].CCN(C(C)C)C(C)C>O.CN(C)C=O>[NH2:19][C:15]1[C:14]2[C:10]([C:6]3[CH:5]=[C:4]4[C:9](=[CH:8][CH:7]=3)[N:1]([C:53](=[O:54])[CH2:52][C:48]3[CH:47]=[C:46]([CH:51]=[CH:50][CH:49]=3)[C:44]#[N:45])[CH2:2][CH2:3]4)=[CH:11][S:12][C:13]=2[CH:18]=[CH:17][N:16]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 15193972-(3-Cyanophenyl)acetic acidHCID 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 534680353-{2-[5-(4-aminothieno[3,2-c]pyridin-3-yl)-2,3-dihydro-1H-indol-1-yl]-2-oxoethyl}benzonitrileYield 74.6%

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, 0.329 mmol) followed by HATU (125 mg, 0.329 mmol), 3-cyanophenylacetic acid (53.0 mg, 0.329 mmol) and DIEA (0.230 mL, 1.317 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-{2-[5-(4-aminothieno[3,2-c]pyridin-3-yl)-2,3-dihydro-1H-indol-1-yl]-2-oxoethyl}benzonitrile (100.8 mg). 1H NMR (400 MHz, DMSO-d6) d ppm 8.13 (d, J=8.1 Hz, 1H) 7.83 (d, J=5.8 Hz, 1H) 7.73-7.79 (m, 2H) 7.66 (d, J=7.8 Hz, 1H) 7.52-7.61 (m, 1H) 7.44 (s, 1H) 7.35 (s, 1H) 7.28 (d, J=5.6 Hz, 1H) 7.20-7.26 (m, 1H) 5.48 (br. s., 2H) 4.29 (t, J=8.5 Hz, 2H) 4.00 (s, 2H) 3.27 (t, 2H).

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-a7373635c00241e0bccb1e6c5490dcb1
Source dataset
uspto-grants-2013_12
Patent number
US08598156B2

Reaction notes

Loading…