Diisopropylamine → HCID 11398881, compound

HRID 1985808Notes

Reaction equation

HRID 1985808 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][S:9]([CH2:12][C@H:13]([NH:17][C@@H:18]([C:23]2[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=2)[C:19]([F:22])([F:21])[F:20])[C:14]([OH:16])=O)(=[O:11])=[O:10])=[CH:4][CH:3]=1.[NH2:30][C:31]1([C:37]#[N:38])[CH2:36][CH2:35][S:34][CH2:33][CH2:32]1.C(NC(C)C)(C)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1>CN(C=O)C>[C:37]([C:31]1([NH:30][C:14](=[O:16])[C@@H:13]([NH:17][C@@H:18]([C:23]2[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=2)[C:19]([F:20])([F:21])[F:22])[CH2:12][S:9]([CH2:8][C:5]2[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=2)(=[O:10])=[O:11])[CH2:36][CH2:35][S:34][CH2:33][CH2:32]1)#[N:38]

Participants

6

Reactant 4

HCID 7912DiisopropylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 158187404-Aminothiane-4-carbonitrileHCID 68863381HCID 68863381, compound

Product 1

HCID 11398881HCID 11398881, compoundYield 16%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

3-(4-Fluorophenylmethanesulfonyl)-2(R)-[2,2,2-trifluoro-1(S)-(4-fluorophenyl)-ethylamino]propionic acid (146 mg) and 4-aminotetrahydrothiopyran-4-carbonitrile (104 mg) were weighed into a 4 mL vial fitted with a stir bar and cap and DMF (2 mL) was added to give a dark amber solution. Diisopropylamine (0.23 mL) and O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (271 mg) were added and the vial was flushed the vial with nitrogen and sealed with the cap. After 1 h, the reaction mixture was diluted with a 9:1 mixture of CH2Cl2:EtOAc (40 mL)) and washed with 1.0M aqueous KHSO4, water, a 1:1 H2O: saturated aqueous NaHCO3, and brine and dried over anhydrous MgSO4. After concentration, the residue was purified by flash chromatography on 20 cm3 silica gel using 9:1 CHCl3: EtOAc eluent to give the N-(4-cyanotetrahydrothiopyran-4-yl)-3-(4-fluorophenylmethanesulfonyl)-2(R)-(2,2,2-trifluoro-1(S)-4-fluorophenylethylamino)-propionamide (30 mg) as a beige solid.

Workup

  1. customvial fitted with a stir bar
  2. customcap
  3. customto give a dark amber solution
  4. customthe vial was flushed the vial with nitrogen
  5. customsealed with the cap
  6. additionthe reaction mixture was diluted with a 9:1 mixture of CH2Cl2
  7. washEtOAc (40 mL)) and washed with 1.0M aqueous KHSO4, water
  8. dry with materiala 1:1 H2O: saturated aqueous NaHCO3, and brine and dried over anhydrous MgSO4
  9. concentrationAfter concentration
  10. customthe residue was purified by flash chromatography on 20 cm3 silica gel using 9:1 CHCl3

Sources & evidence

ORD record
ord-fcc46838f1d74724b5576573406de838
Source dataset
uspto-grants-2009_06
Patent number
US07547701B2

Reaction notes

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