Terephthalic Acid → HCID 118677383, compound

HRID 1481936Notes

Reaction equation

HRID 1481936 reaction equation
[C:1]([O:5][C:6](=[O:42])[N:7]([C@H:9]([C:11](=[O:41])[NH:12][C@@H:13]1[C:19](=[O:20])[N:18]([CH2:21][C:22]2[C:31]3[C:26](=[CH:27][C:28]([Br:32])=[CH:29][CH:30]=3)[CH:25]=[CH:24][C:23]=2[O:33][CH3:34])[C:17]2[CH:35]=[CH:36][C:37]([C:39]#[N:40])=[CH:38][C:16]=2[NH:15][CH2:14]1)[CH3:10])[CH3:8])([CH3:4])([CH3:3])[CH3:2].[C:43]([OH:54])(=O)[C:44]1[CH:52]=[CH:51][C:47]([C:48]([OH:50])=O)=[CH:46][CH:45]=1.O=P(Cl)(Cl)Cl>N1C=CC=CC=1>[Br:32][C:28]1[CH:27]=[C:26]2[C:31](=[CH:30][CH:29]=1)[C:22]([CH2:21][N:18]1[C:17]3[CH:35]=[CH:36][C:37]([C:39]#[N:40])=[CH:38][C:16]=3[N:15]([C:48](=[O:50])[C:47]3[CH:46]=[CH:45][C:44]([C:43]([N:15]4[C:16]5[CH:38]=[C:37]([C:39]#[N:40])[CH:36]=[CH:35][C:17]=5[N:18]([CH2:21][C:22]5[C:31]6[C:26](=[CH:27][C:28]([Br:32])=[CH:29][CH:30]=6)[CH:25]=[CH:24][C:23]=5[O:33][CH3:34])[C:19](=[O:20])[C@@H:13]([NH:12][C:11](=[O:41])[C@@H:9]([N:7]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:42])[CH3:8])[CH3:10])[CH2:14]4)=[O:54])=[CH:52][CH:51]=3)[CH2:14][C@H:13]([NH:12][C:11](=[O:41])[C@@H:9]([N:7]([CH3:8])[C:6](=[O:42])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4])[CH3:10])[C:19]1=[O:20])=[C:23]([O:33][CH3:34])[CH:24]=[CH:25]2

Participants

5

Reactant 3

HCID 7489Terephthalic AcidHCID 24813Phosphorus oxychlorideHCID 90220908HCID 90220908, compound2×

Product 1

HCID 118677383HCID 118677383, compoundYield 4.5%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of {(S)-1-[(S)-1-(6-bromo-2-methoxy-naphthalen-1-ylmethyl)-7-cyano-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylcarbamoyl]-ethyl}-methyl-carbamic acid tert-butyl ester (Intermediate 4) (120 mg, 0.189 mmol) in pyridine (2 mL) was added terephthalic acid (20.604 mg, 0.113 mmol). After 10 min, the mixture was cooled to 0° C., POCl3 (0.036 mL, 0.396 mmol) was added and the cooling bath was removed. After 1 h, the mixture was concentrated, the residue was diluted with ethyl acetate and filtered. The filtrate was concentrated and the residue was purified by preparative HPLC to provide tert-butyl N-[(1S)-2-[[(3S)-1-[(6-bromo-2-methoxy-1-naphthyl)methyl]-5-[4-[(3S)-1-[(6-bromo-2-methoxy-1-naphthyl)methyl]-3-[[(2S)-2-[tert-butoxycarbonyl(methyl)amino]propanoyl]amino]-7-cyano-2-oxo-3,4-dihydro-1,5-benzodiazepine-5-carbonyl]benzoyl]-7-cyano-2-oxo-3,4-dihydro-1,5-benzodiazepin-3-yl]amino]-1-methyl-2-oxo-ethyl]-N-methyl-carbamate (6 mg, 1%) as an off white solid. LC-MS: 1403.2 (M+H).

Workup

  1. customthe cooling bath was removed
  2. waitAfter 1 h
  3. concentrationthe mixture was concentrated
  4. additionthe residue was diluted with ethyl acetate
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated
  7. customthe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-489291ec37f14dc7ac241fddf5c5edfe
Source dataset
uspto-grants-2016_08
Patent number
US09409888B2

Reaction notes

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