Cesium carbonate → Tert-butyl 3-(2-(7-(trifluoromethyl)isoquinolin-1-ylamino)acetamido)azetidine-1-carboxylate

HRID 1896962Notes

Reaction equation

Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([C:12]([F:15])([F:14])[F:13])[CH:10]=2)[CH:5]=[CH:4][N:3]=1.[NH2:16][CH2:17][C:18]([NH:20][CH:21]1[CH2:24][N:23]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:22]1)=[O:19].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].C1(C)C=CC=CC=1>[F:13][C:12]([F:15])([F:14])[C:9]1[CH:10]=[C:11]2[C:6]([CH:5]=[CH:4][N:3]=[C:2]2[NH:16][CH2:17][C:18]([NH:20][CH:21]2[CH2:24][N:23]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:22]2)=[O:19])=[CH:7][CH:8]=1

Participants

Conditions

Temperature: 100 °C

Procedure

Into a 8 mL sealed tube, was placed 1-chloro-7-(trifluoromethyl)isoquinoline (as prepared in the previous step, 433 mg, 1.87 mmol, 1.00 equiv), tert-butyl 3-(2-aminoacetamido)azetidine-1-carboxylate (prepared as described in Example 1, Step E) (460 mg, 2.01 mmol, 1.18 equiv), Pd(OAc)2 (15 mg, 0.07 mmol, 0.05 equiv), Cs2CO3 (1500 mg, 4.60 mmol, 1.77 equiv), BINAP (30 mg, 0.05 mmol, 0.04 equiv) and toluene (2 mL). The reaction mixture was stirred for 12 h at 100° C. in an oil bath. The solids were filtered off. The resulting mixture was concentrated under vacuum. The residue was purified by chromatography over a silica gel column with ethyl acetate:retroleum ether (1:3). The title compound was obtained as an off white solid.

Workup

customInto a 8 mL sealed tube
filtrationThe solids were filtered off
concentrationThe resulting mixture was concentrated under vacuum
customThe residue was purified by chromatography over a silica gel column with ethyl acetate

Sources & evidence

ORD record: ord-fe867b32448b49bc9870b80b380dac34
Source dataset: uspto-grants-2013_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08518969B2

Reaction notes

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