Hydrochloric Acid → HCID 53374052, compound

HRID 1037951Notes

Reaction equation

HRID 1037951 reaction equation
[F:1][C:2]([F:28])([F:27])[C:3]1[CH:8]=[CH:7][C:6]([S:9]([NH:12][C@@H:13]([C:15]2[S:19][C:18]([C:20](OC(C)(C)C)=[O:21])=[CH:17][CH:16]=2)[CH3:14])(=[O:11])=[O:10])=[CH:5][CH:4]=1.FC(F)(F)C(O)=O.CN(C([O:43][N:44]1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C.[Si](ON)(C(C)(C)C)(C)C.Cl.C([O-])(O)=O.[Na+]>C(Cl)Cl.CN(C)C=O.ClCCCl>[OH:43][NH:44][C:20]([C:18]1[S:19][C:15]([C@H:13]([NH:12][S:9]([C:6]2[CH:7]=[CH:8][C:3]([C:2]([F:28])([F:27])[F:1])=[CH:4][CH:5]=2)(=[O:11])=[O:10])[CH3:14])=[CH:16][CH:17]=1)=[O:21]

Participants

11

Reactant 7

HCID 313Hydrochloric AcidHCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 4691350O-(tert-Butyldimethylsilyl)hydroxylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67397491HCID 67397491, compound

Product 1

HCID 53374052HCID 53374052, compoundYield 23%

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a 2-dram vial containing crude (R)-tert-butyl 5-(1-(4-(trifluoromethyl)phenylsulfonamido)ethyl)thiophene-2-carboxylate from Step 2 was added 1,2-dichloroethane (2 mL), and trifluoroacetic acid (0.246 mL, 3.20 mmol). After shaking at rt for 4 h, the mixture was evaporated to dryness to give a solid which was azeotroped with toluene (2×5 mL). To the resulting solid residue in another microwave vial was added HATU (0.0912 g, 0.240 mmol), N,N-dimethylformamide (1.5 mL), and triethylamine (0.178 mL, 1.28 mmol). The mixture was stirred for 10 min then O-(tert-butyldimethylsilyl)hydroxylamine (0.0471 g, 0.320 mmol) in DCM (0.5 mL) was added. The solution was shaken at rt for 2 h and then evaporated to dryness to afford a brown oil. To this oil in a microwave vial was added hydrochloric acid (3.5 mL, 1% in IPA). After shaking at rt for 30 min, solid NaHCO3 was added to quench the excess acid and the solvent was then removed. To the resulting solid residue was added DMSO (1.2 mL). After filtration, the DMSO solution was filtered and purified by Gilson prep-HPLC to give the title compound (0.0148 g, 23%) as a white solid. LC-MS: (FA) ES− 393. 1H NMR (Methanol-d4, 300 MHz) δ 7.92 (d, J=8.3 Hz, 2H), 7.76 (d, J=8.3 Hz, 2H), 7.24 (m, 1H), 6.77 (d, J=4.1 Hz, 1H), 4.78 (q, J=7.0 Hz, 1H), 1.44 (d, J=6.8 Hz, 3H).

Workup

  1. customthe mixture was evaporated to dryness
  2. customto give a solid which
  3. customwas azeotroped with toluene (2×5 mL)
  4. stirringThe mixture was stirred for 10 min
  5. stirringThe solution was shaken at rt for 2 h
  6. customevaporated to dryness
  7. customto afford a brown oil
  8. stirringAfter shaking at rt for 30 min
  9. customto quench the excess acid
  10. customthe solvent was then removed
  11. additionTo the resulting solid residue was added DMSO (1.2 mL)
  12. filtrationAfter filtration
  13. filtrationthe DMSO solution was filtered
  14. custompurified by Gilson prep-HPLC

Sources & evidence

ORD record
ord-d4eb7a542c184607b2fe847a1b3ebac5
Source dataset
uspto-grants-2013_10
Patent number
US08546588B2

Reaction notes

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