2-Chloro-5-cyanophenylboronic acid → 3-(2'-Amino-1'-methyl-5'-oxo-2-phenyl-1',5'-dihydrospiro[chroman-4,4'-imidazole]-6-yl)-4-chlorobenzonitrile

HRID 2096415Notes

Reaction equation

[NH2:1][C:2]1[N:3]([CH3:24])[C:4](=[O:23])[C:5]2([C:15]3[C:10](=[CH:11][CH:12]=[C:13](Br)[CH:14]=3)[O:9][CH:8]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH2:7]2)[N:6]=1.[Cl:25][C:26]1[CH:31]=[CH:30][C:29]([C:32]#[N:33])=[CH:28][C:27]=1B(O)O>O1CCOCC1.C([O-])([O-])=O.[Cs+].[Cs+].Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[NH2:1][C:2]1[N:3]([CH3:24])[C:4](=[O:23])[C:5]2([C:15]3[C:10](=[CH:11][CH:12]=[C:13]([C:27]4[CH:28]=[C:29]([CH:30]=[CH:31][C:26]=4[Cl:25])[C:32]#[N:33])[CH:14]=3)[O:9][CH:8]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH2:7]2)[N:6]=1

Participants

Conditions

Temperature: 120 °C

Procedure

Pd(PPh3)2Cl2 (10 mg, 0.01 mmol) in a 10 mL flask under Ar was treated sequentially with 2′-amino-6-bromo-1′-methyl-2-phenylspiro[chroman-4,4′-imidazol]-5′(1′H)-one (20 mg, 0.052 mmol) in 1,4-dioxane (1 mL), Cs2CO3 (2 N, 0.3 mL) and 2-chloro-5-cyanophenylboronic acid (18.9 mg, 0.104 mmol). The mixture was heated at 120° C. under Ar under microwave for 30 min. The reaction mixture was concentrated in vacuo to give the residue, which was purified preparative HPLC twice to give pure 3-(2′-amino-1′-methyl-5′-oxo-2-phenyl-1′,5′-dihydrospiro[chroman-4,4′-imidazole]-6-yl)-4-chlorobenzonitrile (4.2 mg, 18%). 1H-NMR (MeOD): 2.38 (m, 1H), 2.52 (m, 1H), 3.15 (s, 3H), 5.18 & 5.76 (m, 1H), 7.03 & 7.18 (m, 1H), 7.26-7.64 (m, 10H).

Workup

concentrationThe reaction mixture was concentrated in vacuo
customto give the residue, which
customwas purified preparative HPLC twice

Sources & evidence

ORD record: ord-02237759b0bc4e7faea05abfc46602c5
Source dataset: uspto-grants-2013_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08450308B2

Reaction notes

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