3-Morpholino-1-propanol → HCID 71293542, compound

HRID 1402575Notes

Reaction equation

HRID 1402575 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:20]=[CH:21][C:22]=1[NH:23][C:24]([NH:26][C:27]1[CH:32]=[C:31]([CH3:33])[CH:30]=[CH:29][C:28]=1[F:34])=[O:25])[O:5][C:6]1[CH:11]=[CH:10][N:9]=[C:8]([C:12]2[NH:16][CH:15]=[C:14]([C:17]([OH:19])=[O:18])[CH:13]=2)[CH:7]=1.Cl.CN(C)CCCN=C=NCC.O[CH2:48][CH2:49][CH2:50][N:51]1[CH2:56][CH2:55][O:54][CH2:53][CH2:52]1>O1CCCC1.CN(C)C1C=CN=CC=1>[F:1][C:2]1[CH:3]=[C:4]([CH:20]=[CH:21][C:22]=1[NH:23][C:24]([NH:26][C:27]1[CH:32]=[C:31]([CH3:33])[CH:30]=[CH:29][C:28]=1[F:34])=[O:25])[O:5][C:6]1[CH:11]=[CH:10][N:9]=[C:8]([C:12]2[NH:16][CH:15]=[C:14]([C:17]([O:19][CH2:48][CH2:49][CH2:50][N:51]3[CH2:56][CH2:55][O:54][CH2:53][CH2:52]3)=[O:18])[CH:13]=2)[CH:7]=1

Participants

6

Reactant 3

HCID 1995763-Morpholino-1-propanolHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 51001123HCID 51001123, compound

Product 1

HCID 71293542HCID 71293542, compound

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

To a stirred suspension of 5-{4-[3-fluoro-4-({[(2-fluoro-5-methylphenyl)amino]carbonyl}amino)phenoxy]pyridin-2-yl}-1H-pyrrole-3-carboxylic acid (200 mg, 0.43 mmol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDC, 124 mg, 0.65 mmol) in 10 ml of anhydrous tetrahydrofuran were added N-(3-hydroxypropyl)morpholine (125 mg, 0.86 mmol) and 4-dimethylaminopyridine (10 mg, 0.08 mmol). The mixture was heated at 60° C. for 16 hours, cooled to room temperature and evaporated to dryness. The residue was purified by silica gel chromatography eluting with 3˜5% of methanol in chloroform to afford 3-morpholin-4-ylpropyl 5-{4-[3-fluoro-4-({[(2-fluoro-5-methylphenyl)amino]carbonyl}amino)phenoxy]pyridin-2-yl}-1H-pyrrole-3-carboxylate as white solid. Yield: 90 mg, 35%.

Workup

  1. temperaturecooled to room temperature
  2. customevaporated to dryness
  3. customThe residue was purified by silica gel chromatography
  4. washeluting with 3˜5% of methanol in chloroform

Sources & evidence

ORD record
ord-b150a3cdf26041768dfc11a723465a5c
Source dataset
uspto-grants-2014_12
Patent number
US08906944B2

Reaction notes

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