Hydrochloric Acid → HCID 53374160, compound

HRID 588489Notes

Reaction equation

HRID 588489 reaction equation
[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[CH:3]=[C:2]1[C:10]([NH:12][C@@H:13]([C:15]1[S:19][C:18]([C:20]([O:22]C(C)(C)C)=O)=[CH:17][CH:16]=1)[CH3:14])=[O:11].FC(F)(F)C(O)=O.CN(C([O:41][N:42]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>CS(C)=O.C(Cl)Cl>[OH:41][NH:42][C:20]([C:18]1[S:19][C:15]([C@H:13]([NH:12][C:10]([C:2]2[S:1][C:5]3[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=3[CH:3]=2)=[O:11])[CH3:14])=[CH:16][CH:17]=1)=[O:22]

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 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 67397401HCID 67397401, compound

Product 1

HCID 53374160HCID 53374160, compoundYield 10.1%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 6344DichloromethaneSolvent2×

Procedure

To the vial containing crude (R)-tert-butyl 5-(1-(benzothiophene-2-carboxamido)ethyl)thiophene-2-carboxylate from Step 2 was added DCM (4 mL) and trifluoroacetic acid (0.43 mL, 5.6 mmol). The mixture was stirred at rt for 16 h and then completely evaporated to give an oil residue. To the residue was added HATU (0.160 g, 0.42 mmol), triethylamine (0.39 mL, 2.80 mmol), and DCM (4 mL). After stirring at rt for 30 min, O-(tert-butyldimethylsilyl)hydroxylamine (0.083 g, 0.56 mmol) was added. The mixture was stirred at rt for 2 h then the solvent was completely removed to give a sticky brown oil. To this oil residue was added hydrochloric acid (6.0 mL, 1% v/v in IPA). After stirring at rt for 30 min, the mixture was evaporated to dryness to give a solid to which was added DMSO (1.1 mL). The solution was filtered and purified by Gilson prep-HPLC [25-50% MeCN—H2O] to give the title compound (0.0098 g, 10.1%) as a white solid. LC-MS: (FA) ES+ 347; 1H NMR (Methanol-d4, 400 MHz) δ 8.00 (s, 1H), 7.89 (m, 2H), 7.42 (m, 3H), 7.06 (d, J=4.0 Hz, 1H), 5.51 (q, J=7.5 Hz, 1H), 1.69 (d, J=7.0 Hz, 3H).

Workup

  1. customcompletely evaporated
  2. customto give an oil residue
  3. stirringAfter stirring at rt for 30 min
  4. stirringThe mixture was stirred at rt for 2 h
  5. customthe solvent was completely removed
  6. customto give a sticky brown oil
  7. stirringAfter stirring at rt for 30 min
  8. customthe mixture was evaporated to dryness
  9. customto give a solid to which
  10. filtrationThe solution was filtered
  11. custompurified by Gilson prep-HPLC [25-50% MeCN—H2O]

Sources & evidence

ORD record
ord-b8a7dfd5d1474e52bafff764d5fee365
Source dataset
uspto-grants-2016_01
Patent number
US09227951B2

Reaction notes

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