Trifluoroacetic acid → 3-fluoro-5-morpholin-4-yl-N-[4-(3-morpholin-4-yl-propenyl)-naphthalen-1-yl]-benzamide

HRID 1171407Notes

Reaction equation

HRID 1171407 reaction equation
C(OC(=O)[NH:7][C:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11]([CH:18]=[CH:19][CH2:20][N:21]2[CH2:26][CH2:25][O:24][CH2:23][CH2:22]2)=[CH:10][CH:9]=1)(C)(C)C.FC(F)(F)C(O)=O.[F:35][C:36]1[CH:37]=[C:38]([CH:42]=[C:43]([N:45]2[CH2:50][CH2:49][O:48][CH2:47][CH2:46]2)[CH:44]=1)[C:39]([OH:41])=O.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C>ClCCl.O1CCCC1.CN(C)C=O.C(OCC)(=O)C>[F:35][C:36]1[CH:37]=[C:38]([CH:42]=[C:43]([N:45]2[CH2:50][CH2:49][O:48][CH2:47][CH2:46]2)[CH:44]=1)[C:39]([NH:7][C:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11]([CH:18]=[CH:19][CH2:20][N:21]2[CH2:22][CH2:23][O:24][CH2:25][CH2:26]2)=[CH:10][CH:9]=1)=[O:41]

Participants

10

Reactant 5

HCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 222381233-Fluoro-5-(morpholin-4-yl)benzoic acidHCID 66737911[4-(3-Morpholin-4-yl-propenyl)-naphthalen-1-yl]-carbamic acid tert-butyl ester

Product 1

HCID 667378803-fluoro-5-morpholin-4-yl-N-[4-(3-morpholin-4-yl-propenyl)-naphthalen-1-yl]-benzamideYield 11.8%

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

[4-(3-Morpholin-4-yl-propenyl)-naphthalen-1-yl]-carbamic acid tert-butyl ester (367 mg, 1.0 mmol) is stirred at room temperature in dichloromethane (10 ml) and trifluoroacetic acid (5 ml) for 2 hours. The mixture is then evaporated to dryness. The residue, 3-fluoro-5-morpholinyl benzoic acid (337 mg, 1.5 mmol), HBTU (758 mg, 2.0 mmol) and diisopropylethylamine (0.87 ml, 5.0 mmol) are stirred at room temperature in a mixture of tetrahydrofuran (5 ml) and dimethylformamide (1 ml) for 16 hours. The mixture is then poured into ethyl acetate (100 ml) and washed with water (100 ml). The organic layer is dried over anhydrous sodium sulfate and evaporated to dryness. The residue is purified by column chromatography on silica gel eluted with 50% ethyl acetate in hexanes followed by 2.5% methanol in ethyl acetate to give 3-fluoro-5-morpholin-4-yl-N-[4-(3-morpholin-4-yl-propenyl)-naphthalen-1-yl]-benzamide as a pale yellow oil (56 mg).

Workup

  1. customThe mixture is then evaporated to dryness
  2. washwashed with water (100 ml)
  3. dry with materialThe organic layer is dried over anhydrous sodium sulfate
  4. customevaporated to dryness
  5. customThe residue is purified by column chromatography on silica gel
  6. washeluted with 50% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-94b5d7a9f28d4359b10665303cebda40
Source dataset
uspto-grants-2010_11
Patent number
US07829560B2

Reaction notes

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