Thioglycolic Acid → HCID 89459982, compound

HRID 1776601Notes

Reaction equation

HRID 1776601 reaction equation
[C:1]([O:5][C:6]([N:8]([C:13]1[CH:14]=[C:15]([CH:19]=[CH:20][C:21]=1[O:22][CH3:23])[C:16](O)=[O:17])[S:9]([CH3:12])(=[O:11])=[O:10])=[O:7])([CH3:4])([CH3:3])[CH3:2].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN1CCOCC1.[SH:55][CH2:56][C:57]([OH:59])=[O:58]>CN(C=O)C>[C:1]([O:5][C:6]([N:8]([C:13]1[CH:14]=[C:15]([CH:19]=[CH:20][C:21]=1[O:22][CH3:23])[C:16]([S:55][CH2:56][C:57]([OH:59])=[O:58])=[O:17])[S:9]([CH3:12])(=[O:11])=[O:10])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 1133Thioglycolic Acid2×HCID 79724-MethylmorpholineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 89455725HCID 89455725, compound

Product 1

HCID 89459982HCID 89459982, compoundYield 81.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 3-(N-(tert-butoxycarbonyl)methylsulfonamido)-4-methoxybenzoic acid (0.25 g, 0.724 mmol) in dry DMF (7.5 ml), HATU (0.275 g, 0.724 mmol) and 4-methylmorpholine (0.080 ml, 0.724 mmol) were added, and the resulting solution was stirred under nitrogen at RT until complete conversion of starting acid into the activated ester intermediate (UPLC-MS check). Then 2-mercaptoacetic acid (0.042 ml, 0.603 mmol) was added drop wise, and the reaction was stirred at RT overnight. Additional 2-mercaptoacetic acid (0.008 ml, 0.120 mmol) was added, and the mixture was stirred at the same temperature for 5 days. The solvent was removed under vacuum and the residue was partitioned between EtOAc and HCl 1N; the organic phase was dried over Na2SO4 and the solvent was evaporated. The crude was purified by chromatography on silica gel column (DCM:MeOH=95:5) to afford 2-(3-(N-(tert-butoxycarbonyl)methylsulfonamido)-4-methoxybenzoylthio)acetic acid (0.206 g, 0.491 mmol, 81% yield, MS/ESI+ 419.9 [MH]+). This intermediate was used as such without any further purification.

Workup

  1. stirringthe reaction was stirred at RT overnight
  2. stirringthe mixture was stirred at the same temperature for 5 days
  3. customThe solvent was removed under vacuum
  4. customthe residue was partitioned between EtOAc and HCl 1N
  5. dry with materialthe organic phase was dried over Na2SO4
  6. customthe solvent was evaporated
  7. customThe crude was purified by chromatography on silica gel column (DCM:MeOH=95:5)

Sources & evidence

ORD record
ord-10427dce92b34879808253af8fd895c6
Source dataset
uspto-grants-2016_02
Patent number
US09265768B2

Reaction notes

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