Trifluoromethylsulfonamide → HCID 66654424, compound

HRID 2036210Notes

Reaction equation

HRID 2036210 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:20][CH2:19][C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[C@H:12]1[C:21]1[CH:26]=[C:25]([Cl:27])[CH:24]=[CH:23][C:22]=1[O:28][CH2:29][C:30]([OH:32])=O)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:33][C:34]([F:40])([F:39])[S:35]([NH2:38])(=[O:37])=[O:36].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C.CN(C1C=CN=CC=1)C.CCOC(C)=O>[CH2:1]([O:8][C:9]([N:11]1[CH2:20][CH2:19][C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[C@H:12]1[C:21]1[CH:26]=[C:25]([Cl:27])[CH:24]=[CH:23][C:22]=1[O:28][CH2:29][C:30](=[O:32])[NH:38][S:35]([C:34]([F:40])([F:39])[F:33])(=[O:37])=[O:36])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 79001TrifluoromethylsulfonamideHCID 81531Diisopropylethylamine2×HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 66654114HCID 66654114, compound

Product 1

HCID 66654424HCID 66654424, compound

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of (S)-1-(2-carboxymethoxy-5-chloro-phenyl)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid benzyl ester (138 mg, 0.30 mmol, 1.0 eq.) in DMF (1.2 mL), trifluoromethanesulfonamide (47 mg, 0.30 mmol, 1.0 eq.), HATU (125 mg, 0.33 mmol, 1.1 eq.), DIPEA (103 μL, 0.60 mmol, 2.0 eq.), and DMAP (spatula tip) were added. The resulting mixture was stirred at 50° C. for 18 hours. The mixture was then purified by prep. HPLC (column: Waters XBridge, 30×75 mm, 10 um, UV/MS, basic conditions) and evaporated to give a white-off solid, contaminated with some DIPEA. The contaminated product was redissolved in AcOEt and washed with 1M aq. HCl soln. and sat. aq. NaCl soln. The org. phase was dried over MgSO4, filtered, and concentrated in vacuo to give the desired product as a white-off solid.

Workup

  1. customThe mixture was then purified by prep
  2. customHPLC (column: Waters XBridge, 30×75 mm, 10 um, UV/MS, basic conditions) and evaporated
  3. customto give a white-off solid
  4. washwashed with 1M aq. HCl soln
  5. dry with materialphase was dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-83178bd75c5b44d8a5a5428c94e0f385
Source dataset
uspto-grants-2013_11
Patent number
US08575158B2

Reaction notes

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