Trifluoroacetic acid → HCID 46941284, compound

HRID 2114371Notes

Reaction equation

HRID 2114371 reaction equation
[CH3:1][O:2][C:3]1[CH:17]=[CH:16][C:6]2[N:7]([CH2:12][C:13]([OH:15])=O)[C:8](=[O:11])[CH2:9][O:10][C:5]=2[CH:4]=1.[Li].[C:19]1([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[CH:24]=[CH:23][C:22]([CH:25]([NH:32][CH3:33])[CH2:26][N:27]2[CH2:31][CH2:30][CH2:29][CH2:28]2)=[CH:21][CH:20]=1.C(N(CC)CC)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.FC(F)(F)C(O)=O>CC#N.O.CN(C=O)C>[C:19]1([C:34]2[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=2)[CH:24]=[CH:23][C:22]([CH:25]([N:32]([CH3:33])[C:13](=[O:15])[CH2:12][N:7]2[C:6]3[CH:16]=[CH:17][C:3]([O:2][CH3:1])=[CH:4][C:5]=3[O:10][CH2:9][C:8]2=[O:11])[CH2:26][N:27]2[CH2:31][CH2:30][CH2:29][CH2:28]2)=[CH:21][CH:20]=1

Participants

9

Reactant 6

HCID 6422Trifluoroacetic acid2×HCID 8471TriethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 27567161-([1,1'-Biphenyl]-4-yl)-N-methyl-2-(pyrrolidin-1-yl)ethan-1-amineHCID 3028194LithiumHCID 57488854HCID 57488854, compound

Product 1

HCID 46941284HCID 46941284, compoundYield 56%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 18373917Acetonitrile--water (1/1)Solvent

Procedure

[7-(methyloxy)-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl]acetic acid, lithium salt (106 mg, 0.44 mmol), [1-(4-biphenylyl)-2-(1-pyrrolidinyl)ethyl]methylamine (122 mg, 0.44 mmol), triethylamine (91 uL, 0.66 mmol), and (1H-1,2,3-benzotriazol-1-yloxy)[tris(dimethylamino)]phosphonium hexafluorophosphate (BOP Reagent, 232 mg, 0.524 mmol) were added in that order to a 4 mL screw capped vial that contained 1 mL of anhydrous DMF. The reaction mixture was stirred for 20 hours at room temperature, after which time HPLC (Eclipse XDB-C18, 4.6×250 mm, 5 micron, 1-99% CH3CN/H2O with 0.1% trifluoroacetic acid) showed that the reaction was complete. The solvent was removed under vacuum and the residue was dissolved in 2 mL of DMSO, filtered through a 0.2 um PTFE Acrodisk, and purified by reverse-phase HPLC (Phenomenex C-18, 50×100 mm, 80 mL/min, A: acetonitrile (0.1% TFA) B: water (0.1% TFA), A: 15 to 98% over 20 min, UV detection at 214 nm) to give the title compound (123 mg, 0.246 mmol, 56%) as the TFA salt in the form of an off-white solid. MS (ES) m/e 501 [M+H]+.

Workup

  1. customcapped vial
  2. customThe solvent was removed under vacuum
  3. dissolutionthe residue was dissolved in 2 mL of DMSO
  4. filtrationfiltered through a 0.2 um PTFE Acrodisk
  5. custompurified by reverse-phase HPLC (Phenomenex C-18, 50×100 mm, 80 mL/min
  6. waitA: acetonitrile (0.1% TFA) B: water (0.1% TFA), A: 15 to 98% over 20 min

Sources & evidence

ORD record
ord-864532aa159d463ea590f4c0f3bbdebc
Source dataset
uspto-grants-2008_10
Patent number
US07432258B2

Reaction notes

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