Diisopropylethylamine → ethyl 3-((5-fluoro-2-(5-fluoro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-yl)amino)-3-(1-methylcyclopentyl)propanoate

HRID 1055047Notes

Reaction equation

HRID 1055047 reaction equation
[NH2:1][CH:2]([C:9]1([CH3:14])[CH2:13][CH2:12][CH2:11][CH2:10]1)[CH2:3][C:4]([O:6][CH2:7][CH3:8])=[O:5].[F:15][C:16]1[CH:17]=[C:18]2[C:24]([C:25]3[N:30]=[C:29](S(C)=O)[C:28]([F:34])=[CH:27][N:26]=3)=[CH:23][N:22]([S:35]([C:38]3[CH:43]=[CH:42][C:41]([CH3:44])=[CH:40][CH:39]=3)(=[O:37])=[O:36])[C:19]2=[N:20][CH:21]=1.C(N(CC)C(C)C)(C)C>C1COCC1>[F:34][C:28]1[C:29]([NH:1][CH:2]([C:9]2([CH3:14])[CH2:10][CH2:11][CH2:12][CH2:13]2)[CH2:3][C:4]([O:6][CH2:7][CH3:8])=[O:5])=[N:30][C:25]([C:24]2[C:18]3[C:19](=[N:20][CH:21]=[C:16]([F:15])[CH:17]=3)[N:22]([S:35]([C:38]3[CH:43]=[CH:42][C:41]([CH3:44])=[CH:40][CH:39]=3)(=[O:37])=[O:36])[CH:23]=2)=[N:26][CH:27]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 672853275-Fluoro-3-[5-fluoro-4-(methylsulfinyl)-2-pyrimidinyl]-1-[(4-methylphenyl)sulfonyl]-1H-pyrrolo[2,3-b]pyridine2×HCID 86714738Ethyl 3-amino-3-(1-methylcyclopentyl)propanoate2×

Product 1

HCID 71247948ethyl 3-((5-fluoro-2-(5-fluoro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-yl)amino)-3-(1-methylcyclopentyl)propanoate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

A suspension of ethyl 3-amino-3-(1-methylcyclopentyl)propanoate, 33a, (0.20 g, 1.00 mmol), 5-fluoro-3-(5-fluoro-4-methylsulfinyl-pyrimidin-2-yl)-1-(p-tolylsulfonyl)-pyrrolo[2,3-b]pyridine, 25a (0.54 g, 1.20 mmol), and N,N-diisopropylethylamine (0.26 mL, 1.50 mmol) in THF (14.4 mL) was refluxed at 80° C. overnight. After removing the solvent in vacuo, the crude product was purified by silica gel chromatography (0-50% EtOAc/Hexanes gradient) to afford 300 mg of the desired product as a light yellow solid: 1H NMR (400 MHz, CDCl3) δ 8.49 (dd, J=9.0, 2.8 Hz, 1H), 8.46 (s, 1H), 8.23 (d, J=1.5 Hz, 1H), 8.02 (d, J=8.3 Hz, 2H), 7.99 (d, J=3.1 Hz, 1H), 7.20 (d, J=7.8 Hz, 2H), 5.23 (d, J=8.9 Hz, 1H), 4.80 (td, J=9.7, 3.6 Hz, 1H), 4.04 (q, J=7.1 Hz, 1H), 3.91 (q, J=7.1 Hz, 2H), 2.73-2.58 (m, 1H), 2.44 (dd, J=14.7, 9.6 Hz, 1H), 2.33-2.21 (m, 3H), 1.72-1.46 (m, 7H), 1.42-1.31 (m, 1H), 1.28 (t, J=6.1 Hz, 1H), 1.17 (dd, J=13.4, 6.2 Hz, 2H), 0.98 (t, J=7.1 Hz, 6H); LCMS Gradient 10-90%, 0.1% formic acid, 5 minutes, C18/ACN, RT=4.25 minutes (M+H) 584.29.

Workup

  1. customAfter removing the solvent in vacuo
  2. customthe crude product was purified by silica gel chromatography (0-50% EtOAc/Hexanes gradient)

Sources & evidence

ORD record
ord-84973180db98408c8ca03231544d932f
Source dataset
uspto-grants-2016_07
Patent number
US09394302B2

Reaction notes

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