Trifluoroacetic acid → HCID 11478106, compound

HRID 969787Notes

Reaction equation

HRID 969787 reaction equation
[C:1]([O:5][C:6](=O)[NH:7][C@H:8]([C:14](=[O:34])[NH:15][C@H:16]([CH2:23][N:24]1[C:32]2[C:27](=[CH:28][C:29]([F:33])=[CH:30][CH:31]=2)[CH2:26][CH2:25]1)[CH2:17][CH2:18][S:19]([CH3:22])(=[O:21])=[O:20])[CH2:9][C:10]([CH3:13])([CH3:12])[CH3:11])(C)([CH3:3])[CH3:2].FC(F)(F)C(O)=O.CN(C(ON1N=N[C:53]2[CH:54]=CC=N[C:52]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C([N:70](C(C)C)CC)(C)C.C(=O)(O)[O-].[Na+]>ClCCl.O>[F:33][C:29]1[CH:28]=[C:27]2[C:32](=[CH:31][CH:30]=1)[N:24]([CH2:23][C@@H:16]([NH:15][C:14](=[O:34])[C@@H:8]([NH:7][C:6]1[O:5][C:1]3[CH:2]=[CH:54][CH:53]=[CH:52][C:3]=3[N:70]=1)[CH2:9][C:10]([CH3:13])([CH3:12])[CH3:11])[CH2:17][CH2:18][S:19]([CH3:22])(=[O:21])=[O:20])[CH2:25][CH2:26]2

Participants

8

Reactant 5

HCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 69196272HCID 69196272, compound

Product 1

HCID 11478106HCID 11478106, compoundYield 76%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

{1-(S)-[1-(S)-(5-Fluoro-2,3-dihydro-indol-1-ylmethyl)-3-methanesulfonyl-propylcarbamoyl]-3,3-dimethyl-butyl}-carbamic acid tert-butyl ester. The intermediate from Step A (500 mg, 1.29 mmol) was treated with 2 mL of a solution containing 45% trifluoroacetic acid, 45% dichloromethane and 10% water. The material was allowed to stand overnight and the solvent was removed. The resulting oil was treated with Boc-(L)-tBu-Ala (350 mg, 1.42 mmol), HATU (540 mg, 1.42 mmol) and dichloromethane (5 mL). The resulting suspension was treated with diisopropylethylamine (836 mg, 6.47 mmol) and allowed to stir overnight. The reaction contents were then poured into a separatory funnel and treated with saturated aqueous sodium bicarbonate solution. The aqueous layer was extracted with dichloromethane a total of 2 times and discarded. The comined organics were dried over MgSO4 and the solvent was removed. The residue was purified by automated silica gel chromatography using a linear gradient of 0 to 100% ethyl acetate in hexane to afford the title compound as a solid (506 mg, 76%): 1H NMR (CDCl1, 400 MHz) δ 0.74 (s, 9H), 1.41 (dd, 1H, J1=8.3, J2=14.5), 1.70 (dd, 1H, J1=4.4, J2=14.5), 2.57-2.72 (m, 2H), 2.85 (dd, 1H, J1=6.8, J2=13.6), 3.02 (dd, 1H, J1=7.7, J2=13.6), 3.07 (dd, 1H, J1=8.7, J2=17.4), 3.17-3.26 (m, 1H), 3.48 (dd, 1H, J1=4.5, J2=11.4), 3.55 (dd, 1H, J1=3.4, J2=11.4), 3.60 (s, 3H), 3.88-3.98 (m, 1H), 4.43 (ddd, 1H, J1=4.3, J2=8.1, J3=12.3), 6.16 (dd, 1H, J1=4.1, J2=8.5), 6.41 (d, 1H, J=7.7), 6.48 (ddd, 1H, J1=2.6, J2=J3=9.0), 6.52-6.56 (m, 1H), 6.75-6.79 (m, 1H), 6.78-6.84 (m, 1H), 6.98-7.10 (m, 3H); HPLC-MS calcd. for C25H40FN3O5S (M+H+) 514.3, found 514.5.

Workup

  1. customthe solvent was removed
  2. customThe reaction contents
  3. additionwere then poured into a separatory funnel
  4. extractionThe aqueous layer was extracted with dichloromethane a total of 2 times
  5. dry with materialThe comined organics were dried over MgSO4
  6. customthe solvent was removed
  7. customThe residue was purified by automated silica gel chromatography

Sources & evidence

ORD record
ord-45c71abd5d4c4a4785ef115f94a7285d
Source dataset
uspto-grants-2007_12
Patent number
US07307095B2

Reaction notes

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