Diisopropylethylamine → HCID 11341950, compound

HRID 2377542Notes

Reaction equation

HRID 2377542 reaction equation
C(OC([N:11]([CH2:21][C@H:22]([NH:28][C:29](=[O:34])[CH2:30][C:31]([OH:33])=O)[C@@H:23]([OH:27])[CH2:24][CH2:25][CH3:26])[CH2:12][C:13]1[CH:18]=[CH:17][C:16]([CH3:19])=[CH:15][C:14]=1[CH3:20])=O)C1C=CC=CC=1.[Br:35][C:36]1[CH:37]=[C:38]([CH:40]=[C:41]([C:43]([F:46])([F:45])[F:44])[CH:42]=1)[NH2:39].C(N(CC)C(C)C)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl.CN(C=O)C>[Br:35][C:36]1[CH:37]=[C:38]([NH:39][C:31](=[O:33])[CH2:30][C:29]([NH:28][C@@H:22]([CH2:21][NH:11][CH2:12][C:13]2[CH:18]=[CH:17][C:16]([CH3:19])=[CH:15][C:14]=2[CH3:20])[C@@H:23]([OH:27])[CH2:24][CH2:25][CH3:26])=[O:34])[CH:40]=[C:41]([C:43]([F:45])([F:46])[F:44])[CH:42]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 27358803-Bromo-5-(trifluoromethyl)anilineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 69287840HCID 69287840, compound

Product 1

HCID 11341950HCID 11341950, compound

Reagents, catalysts & solvents 1

HCID 22350042dichloromethane N,N-dimethylformamideSolvent

Procedure

The compound N-[(1S,2S)-1-{[benzyloxycarbonyl-(2,4-dimethyl-benzyl)-amino]-methyl}-2-hydroxy-pentyl]-malonamic acid (53 mg, 0.22 mmol, see procedure 17b) was dissolved in 4 mL of 1:1 CH2Cl2/DMF. The resultant solution was charged sequentially with 3-bromo-5-trifluoromethylaniline (105 mg, 0.22 mmol), N,N-diisopropylethylamine (0.19 mL, 1.1 mmol) and HATU (102 mg, 0.27 mmol). The mixture was stirred for 12 h at RT, concentrated in vacuo, and partitioned between EtOAc and sat. NH4Cl. The aqueous phase was extracted with EtOAc (1×). The combined organic extracts were washed with sat. NaHCO3 and brine, dried (Na2SO4), filtered, and concentrated in vacuo. A portion (25 mg) of this product was dissolved in 30% HBr/Acetic acid (2 mL). The solution was stirred for 4 h at RT and concentrated in vacuo. The residue was dissolved in benzene and the resultant solution was concentrated residue; this procedure was repeated. Purification of the residue by reverse-phase HPLC provided the title compound as a white powder after lyopholization. MS found: (M+H)+=560.2.

Workup

  1. concentrationconcentrated in vacuo
  2. custompartitioned between EtOAc and sat. NH4Cl
  3. extractionThe aqueous phase was extracted with EtOAc (1×)
  4. washThe combined organic extracts were washed with sat. NaHCO3 and brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. dissolutionA portion (25 mg) of this product was dissolved in 30% HBr/Acetic acid (2 mL)
  9. stirringThe solution was stirred for 4 h at RT
  10. concentrationconcentrated in vacuo
  11. dissolutionThe residue was dissolved in benzene
  12. customPurification of the residue by reverse-phase HPLC

Sources & evidence

ORD record
ord-d5f43d680a3145c4bc7db5f32b5bd78a
Source dataset
uspto-grants-2008_12
Patent number
US07468440B2

Reaction notes

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