2-(Dimethylamino)ethanol → N-[4-(2,4-difluorophenoxy)-3-(6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-4-yl)phenyl]-N-[2-(dimethylamino)ethyl]ethanesulfonamide

HRID 930927Notes

Reaction equation

HRID 930927 reaction equation
[F:1][C:2]1[CH:31]=[C:30]([F:32])[CH:29]=[CH:28][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][C:8]([NH:11][S:12]([CH2:15][CH3:16])(=[O:14])=[O:13])=[CH:7][C:6]=1[C:17]1[C:18]2[CH:27]=[CH:26][NH:25][C:19]=2[C:20](=[O:24])[N:21]([CH3:23])[CH:22]=1.[CH3:33][N:34]([CH3:38])[CH2:35][CH2:36]O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(/C(OC(C)(C)C)=O)=N\C(OC(C)(C)C)=O>O1CCCC1>[F:1][C:2]1[CH:31]=[C:30]([F:32])[CH:29]=[CH:28][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][C:8]([N:11]([CH2:36][CH2:35][N:34]([CH3:38])[CH3:33])[S:12]([CH2:15][CH3:16])(=[O:14])=[O:13])=[CH:7][C:6]=1[C:17]1[C:18]2[CH:27]=[CH:26][NH:25][C:19]=2[C:20](=[O:24])[N:21]([CH3:23])[CH:22]=1

Participants

6

Reactant 4

HCID 79022-(Dimethylamino)ethanolHCID 11776TriphenylphosphineHCID 6034084Di-tert-butyl diazene-1,2-dicarboxylateHCID 71600087Mivebresib

Product 1

HCID 89657525N-[4-(2,4-difluorophenoxy)-3-(6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-4-yl)phenyl]-N-[2-(dimethylamino)ethyl]ethanesulfonamideYield 31.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of Example 36e (0.15 g, 0.326 mmol), 2-(dimethylamino)ethanol (0.029 g, 0.326 mmol), and triphenylphosphine (0.128 g, 0.490 mmol) in tetrahydrofuran (3 mL) was stirred at ambient temperature for 10 minutes. To this solution was added (E)-di-tert-butyl diazene-1,2-dicarboxylate (0.113 g, 0.490 mmol). The solution was stirred for three hours at ambient temperature. The solvent was removed, and the residue was purified by preparative HPLC (10-80% acetonitrile in 0.1% TFA water) to give the title compound (0.055 g, 0.104 mmol, 31.8% yield). 1H NMR (500 MHz, DMSO-d6) δ ppm 12.06 (s, 1H), 7.51 (d, J=2.44 Hz, 1H), 7.41-7.47 (m, 1H), 7.35-7.37 (m, 2H), 7.23-7.31 (m, 2H), 7.06-7.11 (m, 1H), 6.85 (d, J=8.85 Hz, 1H), 3.57 (t, J=6.71 Hz, 2H), 3.56 (s, 3H), 3.17 (q, J=7.32 Hz, 1H), 2.25 (m, 2H), 2.13 (s, 6H), 1.25 (q, J=7.48 Hz, 3H). MS (ESI+) m/z 531.2 (M+H)+.

Workup

  1. customThe solvent was removed
  2. customthe residue was purified by preparative HPLC (10-80% acetonitrile in 0.1% TFA water)

Sources & evidence

ORD record
ord-c05a91fc21754910b107926196e8d522
Source dataset
uspto-grants-2016_03
Patent number
US09296741B2

Reaction notes

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