Terephthalic Acid → HCID 118677378, compound

HRID 1481934Notes

Reaction equation

HRID 1481934 reaction equation
[C:1]([O:5][C:6](=[O:40])[N:7]([C@H:9]([C:11](=[O:39])[NH:12][C@@H:13]1[C:19](=[O:20])[N:18]([CH2:21][C:22]2[C:31]3[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=3)[CH:25]=[CH:24][C:23]=2[CH3:32])[C:17]2[CH:33]=[CH:34][C:35]([C:37]#[N:38])=[CH:36][C:16]=2[NH:15][CH2:14]1)[CH3:10])[CH3:8])([CH3:4])([CH3:3])[CH3:2].[C:41]([OH:52])(=O)[C:42]1[CH:50]=[CH:49][C:45]([C:46]([OH:48])=O)=[CH:44][CH:43]=1.O=P(Cl)(Cl)Cl>N1C=CC=CC=1>[C:1]([O:5][C:6]([N:7]([CH3:8])[C@@H:9]([CH3:10])[C:11]([NH:12][C@@H:13]1[C:19](=[O:20])[N:18]([CH2:21][C:22]2[C:31]3[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=3)[CH:25]=[CH:24][C:23]=2[CH3:32])[C:17]2[CH:33]=[CH:34][C:35]([C:37]#[N:38])=[CH:36][C:16]=2[N:15]([C:46]([C:45]2[CH:44]=[CH:43][C:42]([C:41]([N:15]3[C:16]4[CH:36]=[C:35]([C:37]#[N:38])[CH:34]=[CH:33][C:17]=4[N:18]([CH2:21][C:22]4[C:31]5[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=5)[CH:25]=[CH:24][C:23]=4[CH3:32])[C:19](=[O:20])[C@@H:13]([NH:12][C:11](=[O:39])[C@@H:9]([N:7]([CH3:8])[C:6](=[O:40])[O:5][C:1]([CH3:2])([CH3:4])[CH3:3])[CH3:10])[CH2:14]3)=[O:52])=[CH:50][CH:49]=2)=[O:48])[CH2:14]1)=[O:39])=[O:40])([CH3:2])([CH3:3])[CH3:4]

Participants

5

Reactant 3

HCID 7489Terephthalic AcidHCID 24813Phosphorus oxychlorideHCID 90221098HCID 90221098, compound2×

Product 1

HCID 118677378HCID 118677378, compoundYield 5.32%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of {(S)-1-[(S)-7-cyano-1-(2-methyl-naphthalen-1-ylmethyl)-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylcarbamoyl]-ethyl}-methyl-carbamic acid tert-butyl ester (Intermediate 16) (90 mg, 0.166 mmol) in pyridine (1 mL) was added terephthalic acid (13.808 mg, 0.083 mmol). After 10 min the mixture was cooled to 0° C., POCl3 (0.017 mL, 0.183 mmol) was added and the cooling bath was removed. After 1 h, the mixture was concentrated, the residue was dissolved in ethyl acetate and the mixture was washed with water, NaHCO3 solution, and brine, dried over sodium sulfate and concentrated. The residue was purified by preparative reverse phase HPLC to provide tert-butyl N-[(1S)-2-[[(3S)-5-[4-[(3S)-3-[[(2S)-2-[tert-butoxycarbonyl(methyl)amino]propanoyl]amino]-7-cyano-1-[(2-methyl-1-naphthyl)methyl]-2-oxo-3,4-dihydro-1,5-benzodiazepine-5-carbonyl]benzoyl]-7-cyano-1-[(2-methyl-1-naphthyl)methyl]-2-oxo-3,4-dihydro-1,5-benzodiazepin-3-yl]amino]-1-methyl-2-oxo-ethyl]-N-methyl-carbamate as white solid (5 mg, 5.32%). LC-MS: 1213.6 (M+H).

Workup

  1. customthe cooling bath was removed
  2. concentrationthe mixture was concentrated
  3. dissolutionthe residue was dissolved in ethyl acetate
  4. washthe mixture was washed with water, NaHCO3 solution, and brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated
  7. customThe residue was purified by preparative reverse phase HPLC

Sources & evidence

ORD record
ord-e436e1e721f24717aa8c63faa7b0ddf1
Source dataset
uspto-grants-2016_08
Patent number
US09409888B2

Reaction notes

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