Triethylamine → HCID 69313077, compound

HRID 2113618Notes

Reaction equation

HRID 2113618 reaction equation
[C:1]([C:5]1[CH:14]=[CH:13][C:12]([NH:15][C:16]2[C:25]3[C:20](=[CH:21][C:22]([C:26]4[C:31]([C:32]([F:35])([F:34])[F:33])=[CH:30][CH:29]=[CH:28][N:27]=4)=[CH:23][CH:24]=3)[N:19]=[CH:18][N:17]=2)=[CH:11][C:6]=1[O:7][CH2:8][CH2:9]O)([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.CS(Cl)(=O)=O.C(=O)([O-])[O-].[K+].[K+].[CH3:54][O:55][C:56](=[O:62])[C@@H:57]1[CH2:61][CH2:60][CH2:59][NH:58]1>ClCCl.C(#N)C>[CH3:54][O:55][C:56]([CH:57]1[CH2:61][CH2:60][CH2:59][N:58]1[CH2:9][CH2:8][O:7][C:6]1[CH:11]=[C:12]([NH:15][C:16]2[C:25]3[C:20](=[CH:21][C:22]([C:26]4[C:31]([C:32]([F:35])([F:33])[F:34])=[CH:30][CH:29]=[CH:28][N:27]=4)=[CH:23][CH:24]=3)[N:19]=[CH:18][N:17]=2)[CH:13]=[CH:14][C:5]=1[C:1]([CH3:2])([CH3:4])[CH3:3])=[O:62]

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 31297Methanesulfonyl chlorideHCID 853477Methyl L-prolinateHCID 22030405HCID 22030405, compound

Product 1

HCID 69313077HCID 69313077, compound

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

Mix 2-(2-tert-butyl-5-[7-(3-trifluoromethyl-pyridin-2-yl)-quinazolin4-ylamino]-phenoxy}-ethanol (24 mg, 0.05 mmol) and triethyl amine (6 mg, 0.06 mmol) in dichloromethane 1 ml and add methanesulfonyl chloride (6 mg, 0.05 mmol). Stir the solution at room temperature for 1 hour and evaporate to dryness. Re-dissolve the residue in acetonitrile (2 ml), transfer to a sealed tube, add potassium carbonate (13 mg, 0.1 mmol) and L-proline methyl ester (13 mg, 0.1 mmol) and heat the mixture at 80° C. for 8 hours. Partition the residue between ethyl acetate and sodium bicarbonate solution and extract with further ethyl acetate. Dry the combined extracts (MgSO4) and concentrate under reduced pressure. Purify the residue by flash chromatography on silica gel (ethyl acetate) to give the title compound.

Workup

  1. customevaporate to dryness
  2. temperatureheat the mixture at 80° C. for 8 hours
  3. customPartition the residue between ethyl acetate and sodium bicarbonate solution
  4. extractionextract with further ethyl acetate
  5. dry with materialDry the combined extracts (MgSO4)
  6. concentrationconcentrate under reduced pressure
  7. customPurify the residue by flash chromatography on silica gel (ethyl acetate)

Sources & evidence

ORD record
ord-ef9a09946e5a4047b1bf9a232cfe61d2
Source dataset
uspto-grants-2008_10
Patent number
US07432275B2

Reaction notes

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