Trifluoroacetic acid → (1R)-1'-({1-[4-(1H-pyrazol-1-yl)phenyl]cyclopropyl}carbonyl)-3H-spiro[furo[3,4-c]pyridine-1,3'-pyrrolidin]-3-one

HRID 969079Notes

Reaction equation

HRID 969079 reaction equation
CN1CCOCC1.[N:8]1([C:13]2[CH:18]=[CH:17][C:16]([C:19]3([C:22]([OH:24])=O)[CH2:21][CH2:20]3)=[CH:15][CH:14]=2)[CH:12]=[CH:11][CH:10]=[N:9]1.Cl.Cl.[NH:27]1[CH2:31][CH2:30][C:29]2([C:39]3[CH:38]=[CH:37][N:36]=[CH:35][C:34]=3[C:33](=[O:40])[O:32]2)[CH2:28]1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.C(O)(C(F)(F)F)=O>CN(C=O)C>[N:8]1([C:13]2[CH:14]=[CH:15][C:16]([C:19]3([C:22]([N:27]4[CH2:31][CH2:30][C@@:29]5([C:39]6[CH:38]=[CH:37][N:36]=[CH:35][C:34]=6[C:33](=[O:40])[O:32]5)[CH2:28]4)=[O:24])[CH2:20][CH2:21]3)=[CH:17][CH:18]=2)[CH:12]=[CH:11][CH:10]=[N:9]1

Participants

7

Reactant 5

HCID 6422Trifluoroacetic acidHCID 79724-MethylmorpholineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 666621753H-spiro[furo[3,4-c]pyridine-1,3'-pyrrolidin]-3-one dihydrochlorideHCID 666624111-[4-(1H-pyrazol-1-yl)phenyl]cyclopropane-1-carboxylic acid

Product 1

HCID 66662214(1R)-1'-({1-[4-(1H-pyrazol-1-yl)phenyl]cyclopropyl}carbonyl)-3H-spiro[furo[3,4-c]pyridine-1,3'-pyrrolidin]-3-oneYield 30%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

4-Methylmorpholine (55 μL, 0.50 mmol) was added to a mixture of 1-[4-(1H-pyrazol-1-yl)phenyl]cyclopropanecarboxylic acid (0.10 mmol), 3H-spiro[furo[3,4-c]pyridine-1,3′-pyrrolidin]-3-one dihydrochloride (0.026 g, 0.10 mmol), and BOP (0.057 g, 0.11 mmol) in DMF (1 mL). The mixture was stirred at room temperature for 2 hours, then adjusted to be acidic (PH=2.0) with TFA, and then diluted with DMF (0.8 mL). The resulting solution was purified by a prep-LCMS followed by chiral HPLC to give (1R)-1′-({1-[4-(1H-pyrazol-1-yl)phenyl]cyclopropyl}carbonyl)-3H-spiro[furo[3,4-c]pyridine-1,3′-pyrrolidin]-3-one (30%). MS (ESI): (M+H)+=401.1

Workup

  1. customThe resulting solution was purified by

Sources & evidence

ORD record
ord-1cddf1b7397a4a348c0808a1554f5160
Source dataset
uspto-grants-2007_12
Patent number
US07304081B2

Reaction notes

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