2-(Methylamino)ethanol → HCID 20746078, compound

HRID 2308100Notes

Reaction equation

HRID 2308100 reaction equation
[CH3:1][C:2]1[N:3]([C:24](=[O:27])[NH:25][CH3:26])[C:4]2[C:9]([CH:10]=1)=[CH:8][C:7]([O:11][C:12]1[CH:17]=[CH:16][N:15]=[C:14]3[CH:18]=[C:19]([C:21](O)=[O:22])[S:20][C:13]=13)=[CH:6][CH:5]=2.[CH3:28][NH:29][CH2:30][CH2:31][OH:32].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.C([O-])(O)=O.[Na+]>CCOC(C)=O.CN(C=O)C>[OH:32][CH2:31][CH2:30][N:29]([CH3:28])[C:21]([C:19]1[S:20][C:13]2[C:14](=[N:15][CH:16]=[CH:17][C:12]=2[O:11][C:7]2[CH:8]=[C:9]3[C:4](=[CH:5][CH:6]=2)[N:3]([C:24](=[O:27])[NH:25][CH3:26])[C:2]([CH3:1])=[CH:10]3)[CH:18]=1)=[O:22]

Participants

8

Reactant 5

HCID 80162-(Methylamino)ethanolHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 22603639HCID 22603639, compound

Product 1

HCID 20746078HCID 20746078, compoundYield 36%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of DMF was added 7-(2-Methyl-1-methylcarbamoyl-1H-indol-5-yloxy)-thieno[3,2-b]pyridine-2-carboxylic acid (0.1 g, 0.26 mmol), as prepared in step (iv), 2-Methylamino-ethanol (0.025 mL, 0.35 mmol) as well as HATU (0.12 g, 0.32) and DIEA (0.051 mL, 0.32 mmol) then stirred for 3 h. To the solution was added 30 mL of EtOAc portioned between 50/50 NaHCO3 (2×30 mL) and the organic layer dried over Na2SO4 then concentrated via rotor evaporator. The title compound was purified with flash chromatography eluting with EtOAc/CH2Cl2/MeOH (2:1:0.1) and the purified fraction concentrate to afford 7-(2-Methyl-1-methylcarbamoyl-1H-indol-5-yloxy)-thieno[3,2-b]pyridine-2-carboxylic acid (2-hydroxy-ethyl)-methyl-amide as an off-white solid (0.041 g, 36%). HPLC: Rt 3.35 min. (96% area). 1H NMR (DMSO-d3, 400 MHz) δ: 8.46 (1H, d, J=4.3 Hz), 8.22 (1H, bs), 7.90-7.81 (1H, m), 7.61 (1H, d, J=8.6 Hz), 7.34 (1H, s), 7.01 (1H, dd, J=8.6, 2.3 Hz), 6.57 (1H, d, J=5.5 Hz), 6.33 (1H, s), 3.56 (5H, m), 2.96 (2H, bs), 2.81 (3H, d, J=5.5 Hz), 2.43 (3H, s). LCMS (ACPI) M+H+ m/z: 439.1. Anal. (C22H22N4O4S.1.0 H2O.0.3 EtOAc) Calc'd: C, 57.60; H, 5.07; N, 11.63. Found: C, 57.87; H, 4.93; N, 11.25.

Workup

  1. dry with materialthe organic layer dried over Na2SO4
  2. concentrationthen concentrated via rotor evaporator
  3. customThe title compound was purified with flash chromatography
  4. washeluting with EtOAc/CH2Cl2/MeOH (2:1:0.1)
  5. concentrationthe purified fraction concentrate

Sources & evidence

ORD record
ord-931fa91c1315424ea93017b4db884477
Source dataset
uspto-grants-2004_12
Patent number
US06833456B2

Reaction notes

Loading…