Dimethylformamide → HCID 54457812, compound

HRID 1078160Notes

Reaction equation

HRID 1078160 reaction equation
[NH2:1][C@@H:2]1[CH2:8][C:7]2[CH:9]=[CH:10][CH:11]=[CH:12][C:6]=2[CH2:5][N:4]([CH2:13][C:14]2[CH:19]=[CH:18][C:17](C3C=CC=CC=3NC(NC)=O)=[CH:16][CH:15]=2)[C:3]1=[O:31].[C:32]([O:36][C:37]([NH:39][C:40]([CH3:45])([C:42]([OH:44])=O)[CH3:41])=[O:38])([CH3:35])([CH3:34])[CH3:33].[CH2:46]([N:48](CC)CC)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)[C:64]2[CH:65]=[CH:66][CH:67]=[CH:68][C:63]=2N=N1.C[N:81]([CH3:84])[CH:82]=[O:83]>C(Cl)Cl.C(OCC)(=O)C>[C:32]([O:36][C:37]([NH:39][C:40]([CH3:41])([CH3:45])[C:42]([NH:1][C@@H:2]1[CH2:8][C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=2[CH2:13][N:4]([CH2:5][C:6]2[CH:7]=[CH:9][C:10]([C:68]3[CH:67]=[CH:66][CH:65]=[CH:64][C:63]=3[CH2:84][NH:81][C:82]([NH:48][CH3:46])=[O:83])=[CH:11][CH:12]=2)[C:3]1=[O:31])=[O:44])=[O:38])([CH3:33])([CH3:34])[CH3:35]

Participants

8

Reactant 5

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 2733845N-((1,1-dimethylethoxy)carbonyl)-2-methyl-alanineHCID 22864424HCID 22864424, compound

Product 1

HCID 54457812HCID 54457812, compoundYield 111%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 158 mg (0.37 mmol) of the intermediate obtained in Step K in 2.5 mL of methylene chloride and 0.5 mL of dimethylformamide was treated with 112 mg (0.55 mmol, 1.5 eq) of N-t-butoxycarbonyl-2-methylalanine, 0.21 mL of triethylamine (149 mg, 1.48 mmol, 4 eq.), and 261 mg (0.59 mmol, 1.6 eq) of benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate. The mixture was stirred at room temperature for 2 hours, then diluted with 20 mL of ethyl acetate and washed three times with 5% aqueous citric acid, twice with saturated aqueous sodium bicarbonate and once with saturated aqueous sodium chloride. The organic layer was removed, dried over magnesium sulfate, filtered and the filtrate concentrated under vacuum. The residue was purified by silica gel chromatography on silica, eluting with methylene chloride/methanol/ammonium hydroxide (96:3.5:0.5), to afford 250 mg (0.41 mmol, 111%) of the product as a white solid, contaminated with residual solvent. FAB-MS: calculated for C35H43N505 613; found 614 (M+H,25%), 514 (M-BOC, 100%).

Workup

  1. washwashed three times with 5% aqueous citric acid
  2. customThe organic layer was removed
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationthe filtrate concentrated under vacuum
  6. customThe residue was purified by silica gel chromatography on silica
  7. washeluting with methylene chloride/methanol/ammonium hydroxide (96:3.5:0.5)

Sources & evidence

ORD record
ord-cabcba7e0721485488fd0f4df3055af2
Source dataset
uspto-grants-1996_08
Patent number
US05545735

Reaction notes

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