Pivalic acid → 9-(Oxazol-5-yl)-3,4,7,8-tetrahydro-[1,4]diazepino[7,1-a]isoquinoline-2,5-dione

HRID 926318Notes

Reaction equation

I[C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH2:4][CH2:5][N:6]1[C:16](=[O:17])[CH2:15][NH:14][C:13](=[O:18])[CH:12]=[C:7]12.[O:19]1[CH:23]=[CH:22][N:21]=[CH:20]1.C(P(C(C)(C)C)C1C(C)=C(C)C(C)=C(C)C=1C1C(C(C)C)=CC(C(C)C)=CC=1C(C)C)(C)(C)C.C([O-])([O-])=O.[K+].[K+].C(O)(=O)C(C)(C)C>CC(N(C)C)=O.CC([O-])=O.CC([O-])=O.[Pd+2]>[O:19]1[C:23]([C:2]2[CH:11]=[CH:10][CH:9]=[C:8]3[C:3]=2[CH2:4][CH2:5][N:6]2[C:16](=[O:17])[CH2:15][NH:14][C:13](=[O:18])[CH:12]=[C:7]23)=[CH:22][N:21]=[CH:20]1

Participants

Conditions

Temperature: 120 °C

Procedure

112-1. A mixture of 9-iodo-3,4,7,8-tetrahydro-[1,4]diazepino[7,1-a]isoquinoline-2,5-dione (520 mg, 1.47 mmol), oxazole (0.24 mL, 3.67 mmol), Pd(OAc)2 (49 mg, 0.22 mmol), di-tert-butyl(2′,4′,6′-triisopropyl-3,4,5,6-tetramethyl-[1,1′-biphenyl]-2-yl)phosphine (141 mg, 0.29 mmol), K2CO3 (609 mg, 4.40 mmol) and pivalic acid (68 μL, 0.59 mmol) in DMA (4 mL) was heated to 120° C. for 1 h in a microwave reactor. The mixture was then filtered and the filtrate was concentrated in vacuo. Purification of the obtained residue by flash chromatography (SiO2, AcOEt/MeOH 99:1 to 90:10) afforded the title compound (140 mg) as a beige powder. UPLC-MS: MS 296.1 (M+H+); UPLC rt 0.60 min.

Workup

filtrationThe mixture was then filtered
concentrationthe filtrate was concentrated in vacuo
customPurification of the obtained residue by flash chromatography (SiO2, AcOEt/MeOH 99:1 to 90:10)

Sources & evidence

ORD record: ord-4141d46575e84ec98719fdd0bbe61467
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09284331B2

Reaction notes

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