Formic Acid → HCID 89610331, compound

HRID 1507720Notes

Reaction equation

HRID 1507720 reaction equation
C(O)=O.[S:4](Cl)([N:7]=C=O)(=[O:6])=[O:5].[CH3:11][N:12]([CH3:35])[C:13]([C:15]1[N:19]([C:20]2[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=2)[C:18]([C:28]([O:30][CH2:31][CH3:32])=[O:29])=[C:17]([OH:33])[C:16]=1[OH:34])=[O:14]>CN1C(=O)CCC1>[CH3:35][N:12]([CH3:11])[C:13]([C:15]1[N:19]([C:20]2[CH:21]=[CH:22][C:23]([O:26][CH3:27])=[CH:24][CH:25]=2)[C:18]([C:28]([O:30][CH2:31][CH3:32])=[O:29])=[C:17]([OH:33])[C:16]=1[O:34][S:4](=[O:5])(=[O:6])[NH2:7])=[O:14]

Participants

5

Reactant 3

HCID 284Formic AcidHCID 70918Chlorosulfonyl isocyanateHCID 71576576HCID 71576576, compound

Product 1

HCID 89610331HCID 89610331, compoundYield 12.3%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

Formic acid (165 μL, 4.31 mmol) was added dropwise to neat sulfurisocyanatidic chloride (374 μL, 4.31 mmol) at 0° C. with stirring. The reaction mixture allowed to warm to RT and stirred for 2 h, after which a solution of ethyl 5-(dimethylcarbamoyl)-3,4-dihydroxy-1-(4-methoxyphenyl)-1H-pyrrole-2-carboxylate (UL1-012) (0.5 g, 1.44 mmol) in NMP (3 mL) was added dropwise. The reaction mixture was stirred at 0° C. for 30 min and allowed to warm to RT and stirred for a further 2 h. The reaction mixture was partitioned with brine (30 mL) and EtOAc (25 mL), the aqueous layer was extracted with EtOAc (2×25 mL) the combined organics were dried (MgSO4), filtered and solvents removed in vacuo to give a yellow oil. The compound was purified by preparative HPLC (C-18 column, 21.2 mm i.d.×100 mm, 5 micron particle size, gradient 5-95% MeCN in 0.1% aqueous formic acid over 16 min) to afford ethyl 5-(dimethylcarbamoyl)-3-hydroxy-1-(4-methoxyphenyl)-4-(sulfamoyloxy)-1H-pyrrole-2-carboxylate (UL1-068) (76 mg, 12%) as a white solid: m/z 428 (M+H)+ (ES+); 426 (M−H)− (ES−). 1H NMR (400 MHz, DMSO-d6) δ: 8.87 (s, 1H), 7.92 (s, 2H), 7.16-7.08 (m, 2H), 6.96-6.88 (m, 2H), 4.03 (q, J=7.1 Hz, 2H), 3.79 (s, 3H), 2.75 (s, 3H), 2.67 (s, 3H), 1.02 (t, J=7.1 Hz, 3H).

Workup

  1. stirringstirred for 2 h
  2. stirringThe reaction mixture was stirred at 0° C. for 30 min
  3. temperatureto warm to RT
  4. stirringstirred for a further 2 h
  5. customThe reaction mixture was partitioned with brine (30 mL) and EtOAc (25 mL)
  6. extractionthe aqueous layer was extracted with EtOAc (2×25 mL) the combined
  7. dry with materialorganics were dried (MgSO4)
  8. filtrationfiltered
  9. customsolvents removed in vacuo
  10. customto give a yellow oil
  11. customThe compound was purified by preparative HPLC (C-18 column, 21.2 mm i.d.×100 mm, 5 micron particle size, gradient 5-95% MeCN in 0.1% aqueous formic acid over 16 min)

Sources & evidence

ORD record
ord-d718b1b3247b44a6afea56e43cb70a75
Source dataset
uspto-grants-2015_12
Patent number
US09221756B2

Reaction notes

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