Cesium carbonate → Tert-butyl 3-(2-[[7-(pentafluoroethyl)isoquinolin-1-yl]amino]acetamido)azetidine-1-carboxylate

HRID 1896963Notes

Reaction equation

HRID 1896963 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([C:12]([F:18])([F:17])[C:13]([F:16])([F:15])[F:14])[CH:10]=2)[CH:5]=[CH:4][N:3]=1.[NH2:19][CH2:20][C:21]([NH:23][CH:24]1[CH2:27][N:26]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:25]1)=[O:22].C([O-])([O-])=O.[Cs+].[Cs+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>CC([O-])=O.CC([O-])=O.[Pd+2]>[F:17][C:12]([F:18])([C:9]1[CH:10]=[C:11]2[C:6]([CH:5]=[CH:4][N:3]=[C:2]2[NH:19][CH2:20][C:21]([NH:23][CH:24]2[CH2:27][N:26]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:25]2)=[O:22])=[CH:7][CH:8]=1)[C:13]([F:16])([F:15])[F:14]

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 18699815Tert-butyl 3-(2-aminoacetamido)azetidine-1-carboxylateHCID 585624761-Chloro-7-(pentafluoroethyl)isoquinoline

Product 1

HCID 86660469Tert-butyl 3-(2-[[7-(pentafluoroethyl)isoquinolin-1-yl]amino]acetamido)azetidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Conditions

Temperature
120 °C

Procedure

Into a 8 mL sealed tube, was placed 1-chloro-7-(pentafluoroethyl)isoquinoline (as prepared in the previous step, 282 mg, 1.00 mmol, 1.00 equiv), tert-butyl 3-(2-aminoacetamido)azetidine-1-carboxylate (prepared as described in Example 1, Step E) (250 mg, 1.09 mmol, 1.09 equiv), Cs2CO3 (1.0 g, 3.07 mmol, 3.06 equiv), BINAP (24 mg, 0.04 mmol, 0.04 equiv), Pd(OAc)2 (10 mg, 0.04 mmol, 0.04 equiv) and tol (2 mL). The reaction mixture was stirred overnight at 120° C. The resulting mixture was concentrated under vacuum. The residue was purified by chromatography over a silica gel column with dichloromethane/methanol (10:1). This resulted in 0.12 g (25%) of tert-butyl 3-(2-[[7-(pentafluoroethyl)isoquinolin-1-yl]amino]acetamido)azetidine-1-carboxylate as a brown solid.

Workup

  1. customInto a 8 mL sealed tube
  2. concentrationThe resulting mixture was concentrated under vacuum
  3. customThe residue was purified by chromatography over a silica gel column with dichloromethane/methanol (10:1)
  4. customThis resulted in 0.12 g (25%) of tert-butyl 3-(2-[[7-(pentafluoroethyl)isoquinolin-1-yl]amino]acetamido)azetidine-1-carboxylate as a brown solid

Sources & evidence

ORD record
ord-9d54eed564564e00ad59a40faa78bc4c
Source dataset
uspto-grants-2013_08
Patent number
US08518969B2

Reaction notes

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