Binap, (A+-)- → 1-Methyl-6-(2-oxa-6-azaspiro[3,3]heptan-6-yl)-1H-pyrrolo[3,2-b]pyridine-5-carbonitrile

HRID 75312Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]2[N:12]([CH3:13])[CH:11]=[CH:10][C:5]2=[N:6][C:7]=1[C:8]#[N:9].CC(C)([O-:17])C.[Na+].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.O=C1[CH2:70][C:69]2([CH2:73][NH:72][CH2:71]2)[CH2:68]1>CC(N(C)C)=O.C(Cl)Cl.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:13][N:12]1[C:4]2[C:5](=[N:6][C:7]([C:8]#[N:9])=[C:2]([N:72]3[CH2:73][C:69]4([CH2:70][O:17][CH2:68]4)[CH2:71]3)[CH:3]=2)[CH:10]=[CH:11]1

Participants

Conditions

Temperature: 102 °C

Procedure

6-Bromo-1-methyl-1H-pyrrolo[3,2-b]pyridine 5-carbonitrile (300 mg, 1.27 mmol), sodium tert-butoxide (366 mg, 3.81 mmol), racemic BINAP (79 mg, 0.127 mmol), Pd2 dba3 (58 mg, 0.064 mmol), and 2-oxo-6-azaspiro[3,3]heptane, 0.5 oxylic acid salt (274 mg, 1.91 mmol) were combined in DMA (12 mL) under N2. The reaction mixture was heated at 102° C. in a microwave for 1 hour and was then diluted with DCM, washed with brine, dried over MgSO4, and concentrated. Purification by silica gel chromatography (2-5% MeOH in DCM) gave the title compound as a pale yellow solid (222 mg, 69%). 1H NMR (500 MHz, CDCl3) δ ppm 7.21 (d, 1H, J=3.5 Hz), 6.60 (s, 1H), 6.58 (d, 1H, J=3.5 Hz), 4.89 (s, 4H), 4.34 (s, 4H), 3.73 (s, 3H). ESI-MS m/z [M+H]+ calc'd for C14H14F4O, 255; found 255.

Workup

washwashed with brine
dry with materialdried over MgSO4
concentrationconcentrated
customPurification by silica gel chromatography (2-5% MeOH in DCM)

Sources & evidence

ORD record: ord-bdbf1c354c124e98a8cb90f3e907f08f
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08835420B2

Reaction notes

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