6-Bromoisoquinoline → tert-Butyl 8-(isoquinolin-6-yl)-2,8-diazaspiro[4.5]decane-2-carboxylate

HRID 1253703Notes

Reaction equation

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

Participants

Conditions

Temperature: 120 °C

Procedure

Sodium t-butylate (6.24 mmol, 3.0 eq.) was added to a solution of tert-butyl 2,8-diazaspiro[4.5]decane-2-carboxylate (2.08 mmol, 1.0 eq.) and 6-bromoisoquinoline (2.08 mmol, 1.0 eq.) in toluene (10 ml) and the reaction mixture was degassed with N2. BINAP (0.124 mmol, 0.06 eq.) and Pd acetate (0.04 mmol, 0.02 eq.) were added and the mixture was heated at 120° C. for 12 h. The reaction mixture was filtered over Celite and the filtrate was concentrated on a rotary evaporator. The crude product was purified by means of column chromatography (silica gel, 5% methanol in methylene chloride) in order to obtain the desired product. Yield: 52%

Workup

customthe reaction mixture was degassed with N2
filtrationThe reaction mixture was filtered over Celite
concentrationthe filtrate was concentrated on a rotary evaporator
customThe crude product was purified by means of column chromatography (silica gel, 5% methanol in methylene chloride) in order

Sources & evidence

ORD record: ord-3bf872bff1f7480ea9de142df912f99b
Source dataset: uspto-grants-2013_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08455475B2

Reaction notes

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