Tri-o-tolylphosphine → HCID 52950572, compound

HRID 633935Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]2[C:9](=[N:10][CH:11]=1)[NH:8][C:7](=[O:12])[CH:6]([CH2:13][OH:14])[CH2:5]2.CCN(C(C)C)C(C)C.[C:24]([N:28]1[CH2:33][CH2:32][CH:31]([CH2:34][O:35][C:36]2[CH:41]=[CH:40][C:39]([F:42])=[CH:38][CH:37]=2)[CH2:30][CH2:29]1)(=[O:27])[CH:25]=[CH2:26].C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>CN(C=O)C.C(#N)CC.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[OH:14][CH2:13][CH:6]1[CH2:5][C:4]2[C:9](=[N:10][CH:11]=[C:2](/[CH:26]=[CH:25]/[C:24]([N:28]3[CH2:33][CH2:32][CH:31]([CH2:34][O:35][C:36]4[CH:41]=[CH:40][C:39]([F:42])=[CH:38][CH:37]=4)[CH2:30][CH2:29]3)=[O:27])[CH:3]=2)[NH:8][C:7]1=[O:12]

Participants

Conditions

Temperature: 100 °C

Procedure

To a suspension of 6-bromo-3-(hydroxymethyl)-3,4-dihydro-1,8-naphthyridin-2(1H)-one (10 mg, 0.039 mmol; which may be prepared as described in Step 2) in DMF (200 μL) and proprionitrile (200 μL) under Argon were added DIPEA (8 μL, 0.047 mmol), 1-acryloyl-4-[(4-fluorophenoxy)methyl]piperidine (14 mg, 0.053 mmol; which may be prepared as described in Step 1), tri(o-tolyl)phosphine (2 mg, 0.008 mmol) and palladium acetate (1 mg, 0.004 mmol). The mixture was stirred at 100° C. for 2 days, then was allowed to come back to room temperature, filtered through Celite pad. The residue obtained after concentration of the filtrate was purified by preparative TLC (eluent: DCM/MeOH 9/1) to give the title compound as a white solid (1 mg, 6%).

Workup

customto come back to room temperature
filtrationfiltered through Celite pad
customThe residue obtained after concentration of the filtrate
customwas purified by preparative TLC (eluent: DCM/MeOH 9/1)

Sources & evidence

ORD record: ord-ddbf32a3a32f4397bcf34e2773655952
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09321769B2

Reaction notes

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