Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N+:1]([C:4]1[CH:59]=[CH:58][C:7]([O:8][C:9]2[CH:14]=[CH:13][C:12]([N:15]([C:42]3[CH:47]=[CH:46][C:45]([O:48][C:49]4[CH:54]=[CH:53][C:52]([N+:55]([O-])=O)=[CH:51][CH:50]=4)=[CH:44][CH:43]=3)[C:16]3[CH:28]=[CH:27][C:26]4[C:25]5[C:20](=[CH:21][C:22]([C:29]6[S:30][C:31]7[CH:37]=[CH:36][CH:35]=[CH:34][C:32]=7[N:33]=6)=[CH:23][CH:24]=5)[C:19]([CH2:40][CH3:41])([CH2:38][CH3:39])[C:18]=4[CH:17]=3)=[CH:11][CH:10]=2)=[CH:6][CH:5]=1)([O-])=O.CC(N(C)C)=O.C(O)C.O.NN>[Pd].O>[NH2:1][C:4]1[CH:59]=[CH:58][C:7]([O:8][C:9]2[CH:14]=[CH:13][C:12]([N:15]([C:42]3[CH:47]=[CH:46][C:45]([O:48][C:49]4[CH:50]=[CH:51][C:52]([NH2:55])=[CH:53][CH:54]=4)=[CH:44][CH:43]=3)[C:16]3[CH:28]=[CH:27][C:26]4[C:25]5[C:20](=[CH:21][C:22]([C:29]6[S:30][C:31]7[CH:37]=[CH:36][CH:35]=[CH:34][C:32]=7[N:33]=6)=[CH:23][CH:24]=5)[C:19]([CH2:38][CH3:39])([CH2:40][CH3:41])[C:18]=4[CH:17]=3)=[CH:11][CH:10]=2)=[CH:6][CH:5]=1
Reactant: CCC1(CC)c2cc(-c3nc4ccccc4s3)ccc2-c2ccc(N(c3ccc(Oc4ccc([N+](=O)[O-])cc4)cc3)c3ccc(Oc4ccc([N+](=O)[O-])cc4)cc3)cc21
Agent: [Pd]
Agent: NN
Solvent: CCO
Solvent: O
Solvent: CC(=O)N(C)C
Product: CCC1(CC)c2cc(-c3nc4ccccc4s3)ccc2-c2ccc(N(c3ccc(Oc4ccc(N)cc4)cc3)c3ccc(Oc4ccc(N)cc4)cc3)cc21
Temperature: 70 °C
Reaction time: 2 h
Yield: 54 %

Procedure:
To a mixture of N,N-di[4-(4-nitrophenoxy)phenyl)]-7-(benzothiazol-2-yl)-9,9-diethyl-fluoren-2-amine (Example 11; 5.25 g, 6.6 mmol), DMAC (75 mL), ethanol (50 mL), and 10% palladium on charcoal catalyst (0.51 g) heated to 70° C., a mixture of hydrazine hydrate (4.9 mL), and ethanol (7 mL) was added in portions over 15 minutes. After two hours at 75° C., the mixture was cooled and poured into water. The separated solids were collected, and transferred to a column of silica gel. Elution with 3:1 toluene-ethyl-acetate mixture gave the product, 2.61 g (54% yield), m.p. 192-194° C. Recrystallization from a mixture of ethyl acetate and hexanes did not raise the m.p. Mass spec: m/z 736 (M+). Anal. Calcd. for C48H40N4O2S: C, 78.23%; H, 5.47%; N, 7.60%; S, 4.35%. Found: C, 78.23%; H, 5.56%; N, 7.55%; S, 4.41%. 1H NMR (CDCl3) δ ppm: 0.37 (t, 6H, 7.32 Hz), 1.88-1.97 (m, 2H), 2.03-2.11 (m, 2H), 3.57 (s, 4H), 6.64-6.73 (m, 4H), 6.85-6.92 (m, 8H), 6.94-6.98 (m, 1H), 7.00-7.10 (m, 5H), 7.36 (t, 1H, 8.16 Hz), 7.48 (t, 1H, 7.12 Hz), 7.55 (d, 1H, 8.28 Hz), 7.65 (m, 1H, 7.92 Hz), 7.89 (m, 1H, 7.6 Hz), 7.99 (dd, 1H, 1.6 and 7.92 Hz), 8.02-8.10 (m, 2H). 13C NMR (CDCl3) δ ppm: 8.58, 32.59, 56.29 (3 sp3C), 116.19, 116.64, 118.16, 119.09, 120.79, 120.84, 121.26, 121.37, 121.49, 122.86, 124.87, 125.81, 126.21, 127.22, 131.13, 134.12, 134.88, 142.36, 142.55, 144.64, 148.67, 148.86, 150.51, 152.06, 154.23, 154.53, and 168.90 (27 sp2C).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[CH:4][C:5]2[C:9]([CH3:11])([CH3:10])[O:8][B:7]([OH:12])[C:6]=2[CH:13]=1.C([O-])([O-])=O.[K+].[K+].[F:20][C:21]1[CH:29]=[CH:28][C:24]([C:25](Cl)=[O:26])=[C:23]([C:30]([F:33])([F:32])[F:31])[CH:22]=1.C(OC(C)C)(=O)C>O.CC(C)=O.C1COCC1>[F:20][C:21]1[CH:29]=[CH:28][C:24]([C:25]([NH:1][C:2]2[CH:3]=[CH:4][C:5]3[C:9]([CH3:10])([CH3:11])[O:8][B:7]([OH:12])[C:6]=3[CH:13]=2)=[O:26])=[C:23]([C:30]([F:31])([F:32])[F:33])[CH:22]=1
Reactant: CC1(C)OB(O)c2cc(N)ccc21
Reactant: O=C(Cl)c1ccc(F)cc1C(F)(F)F
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(=O)OC(C)C
Solvent: C1CCOC1
Solvent: CC(C)=O
Product: CC1(C)OB(O)c2cc(NC(=O)c3ccc(F)cc3C(F)(F)F)ccc21
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 113.1 %

Procedure:
A 22 L four-necked round-bottomed-flask equipped with a nitrogen inlet adapter, mechanical stirrer and thermocouple was charged with 6-amino-3,3-dimethyl-3H-benzo[c][1,2]oxaborol-1-ol (554 g, 3.13 mol), THF (5.5 L, anhydrous, stabilizer free) and K2CO3 (865 g, 6.26 mol). The suspension was stirred at room temperature for 30 min and 4-fluoro-2-(trifluoromethyl)benzoyl chloride (780 g, 3.44 mol) was added over 30 min. The resulting suspension was aged for 24 h at room temperature. HPLC showed unreacted 6-amino-3,3-dimethyl-3H-benzo[c][1,2]oxaborol-1-ol so an additional 42 mL of the acid chloride was added. After 30 min, water (2.8 L) and isopropyl acetate (5.5 L) were added and the phases were partitioned. The organic phase was further extracted with water (2.8 L) and then brine (2.8 L). The organic phase was dried over MgSO4 and concentrated in vacuo to provide a tan solid. The solid was dissolved with acetone (3.0 L) and transferred to a mechanically stirred 50 L round-bottomed-flask. Distilled water (2.0 L) was added in one portion and the mixture was stirred for 30 min to produce a seed bed and then additional water (1.0 L) was added over 30 min. The suspension was stirred at room temperature overnight and the solids were collected on a frit. The cake was rinsed with 1:1 acetone/water (1.0 L) and air dried to constant weight to provide 4-fluoro-N-(1-hydroxy-3,3-dimethyl-1,3-dihydro-benzo[c][1,2]oxaborol-6-yl)-2-trifluoromethyl benzamide as a dark tan solid (1.3 kg).
Reaction SMILES: [C:1]([C:5]1[CH:10]=[C:9]([SH:11])[CH:8]=[C:7]([C:12]([CH3:15])([CH3:14])[CH3:13])[C:6]=1[OH:16])([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[K+].[K+].Cl[CH2:24][Si:25]([CH3:33])([CH3:32])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1>CN(C)C=O>[C:12]([C:7]1[CH:8]=[C:9]([S:11][CH2:24][Si:25]([CH3:33])([CH3:32])[C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH:10]=[C:5]([C:1]([CH3:4])([CH3:3])[CH3:2])[C:6]=1[OH:16])([CH3:15])([CH3:14])[CH3:13]
Reactant: C[Si](C)(CCl)c1ccccc1
Reactant: CC(C)(C)c1cc(S)cc(C(C)(C)C)c1O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CC(C)(C)c1cc(SC[Si](C)(C)c2ccccc2)cc(C(C)(C)C)c1O
Temperature: 25 °C
Reaction time: 8 h

Procedure:
Mix 2,6-di-t-butyl-4-mercaptophenol (2.4 g, 10mmol), potassium carbonate (1.4 g, 10 mmol), chloromethyldimethylphenylsilane (1.9 g, 10 mmol) and dimethylformamide (50 mL) and stir overnight at room temperature under argon atmosphere. Dilute the mixture with ice-water and extract with ethyl ether. Wash the ethereal layer with water, then brine, filter through flourosil-Na2SO4, and evaporate to an orange oil (3.5 g). Purify the product by first distilling (bp 160°-170° C. @0.1 mm Hg), then subjecting to silica gel chromatography (CCl4 :CHCl3 /1:1) to obtain the title compound as a light yellow oil which slowly crystallizes to a whim waxy solid (2.3 g, 59%).
Reaction SMILES: [NH2:1][C:2]1[N:7]([C:8]2[CH:13]=[CH:12][C:11]([Cl:14])=[C:10]([C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH:9]=2)[C:6](=[O:20])[CH:5]=[C:4]([C:21]([F:24])([F:23])[F:22])[N:3]=1.CO[C:27](OC)([CH2:29]Br)[CH3:28]>CN(C=O)C>[Cl:14][C:11]1[CH:12]=[CH:13][C:8]([N:7]2[C:6](=[O:20])[CH:5]=[C:4]([C:21]([F:23])([F:24])[F:22])[N:3]3[CH:28]=[C:27]([CH3:29])[N:1]=[C:2]23)=[CH:9][C:10]=1[C:15]([O:17][CH2:18][CH3:19])=[O:16]
Reactant: CCOC(=O)c1cc(-n2c(N)nc(C(F)(F)F)cc2=O)ccc1Cl
Reactant: COC(C)(CBr)OC
Solvent: CN(C)C=O
Product: CCOC(=O)c1cc(-n2c(=O)cc(C(F)(F)F)n3cc(C)nc23)ccc1Cl
Temperature: 130 °C

Procedure:
A mixture of 2-amino-3-(4-chloro-3-ethoxycarbonylphenyl)-3,4-dihydro-6-trifluoromethylpyrimidin-4-one (0.5 g), bromoacetone dimethyl acetal (0.6 g) and DMF (10 ml) was heated for 5 hours at 130° C. with stirring. The solvent was distilled off under reduced pressure. The residue was added with water and extracted with ethyl acetate. The extract layer was washed with water and dried on anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure and the residue was purified by a preparative thin-layer plate of alumina (developing solvent: ethyl acetate/hexane=3/7) to give the compound of interest (0.11 g).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:11][C:10](=[CH:12][C:13]2[N:14]([CH3:29])[C:15]3[C:20]([N:21]=2)=[C:19]([N:22]2[CH2:27][CH2:26][O:25][CH2:24][CH2:23]2)[N:18]=[C:17](Cl)[N:16]=3)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH:30]1[C:34]2[CH:35]=[CH:36][CH:37]=[CH:38][C:33]=2[N:32]=[C:31]1[C@H:39]([OH:41])[CH3:40].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.C([O-])([O-])=O.[Cs+].[Cs+]>C1(C)C=CC=CC=1.[Pd].[Pd].C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1>[C:1]([O:5][C:6]([N:8]1[CH2:11][C:10](=[CH:12][C:13]2[N:14]([CH3:29])[C:15]3[C:20]([N:21]=2)=[C:19]([N:22]2[CH2:27][CH2:26][O:25][CH2:24][CH2:23]2)[N:18]=[C:17]([N:30]2[C:34]4[CH:35]=[CH:36][CH:37]=[CH:38][C:33]=4[N:32]=[C:31]2[C@H:39]([OH:41])[CH3:40])[N:16]=3)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: Cn1c(C=C2CN(C(=O)OC(C)(C)C)C2)nc2c(N3CCOCC3)nc(Cl)nc21
Reactant: C[C@@H](O)c1nc2ccccc2[nH]1
Agent: [Pd]
Agent: CC(C)c1cc(C(C)C)c(-c2ccccc2P(C2CCCCC2)C2CCCCC2)c(C(C)C)c1
Agent: O=C(C=Cc1ccccc1)C=Cc1ccccc1
Solvent: Cc1ccccc1
Product: C[C@@H](O)c1nc2ccccc2n1-c1nc(N2CCOCC2)c2nc(C=C3CN(C(=O)OC(C)(C)C)C3)n(C)c2n1
Temperature: 140 °C
Yield: 71 %

Procedure:
A mixture of 3-(2-chloro-9-methyl-6-morpholin-4-yl-9H-purin-8-ylmethylene)azetidine-1-carboxylic acid tert-butyl ester (180 mg, 0.43 mmol), (R)-1-(1H-benzoimidazol-2-yl)ethanol (84 mg, 0.52 mmol), tris(dibenzylideneacetone) dipalladium (40 mg, 0.04 mmol), XPhos (82 mg, 0.17 mmol) and Cs2CO3 (279 mg, 0.86 mmol) in toluene (3 mL) was purged with argon then heated at 140° C. for 1 h in a microwave reactor. The reaction mixture was filtered through Celite®, washing with EtOAc and the filtrate concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, MeOH:EtOAc, 0-15%) affording the title compound (167 mg, 72%). LCMS (method A): RT 3.24 min [M+H]+ 547.4
Reaction SMILES: [C:1](=[O:4])([O-])[O-].[Cs+].[Cs+].[NH:7]1[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[NH:9][C:8]1=O.CI.O>CN(C=O)C>[CH3:8][N:7]1[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[NH:9][C:1]1=[O:4]
Reactant: O=c1[nH]c2ccccc2[nH]1
Reactant: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Solvent: CI
Solvent: O
Product: Cn1c(=O)[nH]c2ccccc21
Reaction time: 0.5 h
Yield: 11.6 %

Procedure:
Cesium carbonate (814.5 mg, 2.5 mmol) was added to a stirred solution of benzimidazolinone (335 mg, 2.5 mmol) in DMF (10 mL) under nitrogen at room temperature. After stirring for 30 min., methyl iodide (355 mg, 2.5 mmol) was added and the mixture stirred at room temperature for 18 h. Water was added and the mixture extracted with ethyl acetate. The organic phase was washed with water, dried (magnesium sulfate) and the solvent removed in vacuo. The residue was chromatographed (10-50% ethyl acetate/hexane) to give the title compound (43 mg, 12%) as a white solid.
Reaction SMILES: [CH2:1]([CH2:3][NH2:4])[OH:2].C([O-])(O)=O.[Na+].[Cl:10][C:11]1[CH:18]=[CH:17][C:14]([CH:15]=O)=[CH:13][CH:12]=1.[BH4-].[Na+]>C1COCC1.CO>[Cl:10][C:11]1[CH:18]=[CH:17][C:14]([CH2:15][NH:4][CH2:3][CH2:1][OH:2])=[CH:13][CH:12]=1
Reactant: O=Cc1ccc(Cl)cc1
Reactant: NCCO
Agent: O=C([O-])O
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Solvent: C1CCOC1
Product: OCCNCc1ccc(Cl)cc1
Temperature: 0 °C
Reaction time: 1 h

Procedure:
To a solution of ethanolamine (1.2 eq.) in either MeOH or THF were added NaHCO3 (1.5 eq.) and 4-chlorobenzaldehyde (1 eq.). The reaction was refluxed for 4 h, then cooled to 0° C. NaBH4 (1.2 eq.) was added portionwise. The reaction was stirred for 1 h at 0° C., then 15 h at 20° C. The crude was concentrated under reduced pressure then partitioned between water and DCM. The aqueous layer was then extracted twice with DCM. The organic layers were combined, dried over MgSO4, filtered and concentrated under reduced pressure. The crude was purified by chromatography on silica gel (elution with DCM/MeOH: 1/0 to 95/5) to afford 2-(4-chloro-benzylamino)-ethanol.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([C:8]2[C:17]3[C:12](=[N:13][C:14]([CH3:18])=[CH:15][CH:16]=3)[N:11]([CH2:19][CH3:20])[C:10](=[O:21])[C:9]=2[CH:22]2[CH2:27][CH2:26][N:25]([CH2:28][C:29]([O:31]CC)=[O:30])[CH2:24][CH2:23]2)[CH:5]=[CH:6][CH:7]=1.[ClH:34]>>[ClH:34].[Br:1][C:2]1[CH:3]=[C:4]([C:8]2[C:17]3[C:12](=[N:13][C:14]([CH3:18])=[CH:15][CH:16]=3)[N:11]([CH2:19][CH3:20])[C:10](=[O:21])[C:9]=2[CH:22]2[CH2:27][CH2:26][N:25]([CH2:28][C:29]([OH:31])=[O:30])[CH2:24][CH2:23]2)[CH:5]=[CH:6][CH:7]=1
Reactant: CCOC(=O)CN1CCC(c2c(-c3cccc(Br)c3)c3ccc(C)nc3n(CC)c2=O)CC1
Agent: Cl
Product: CCn1c(=O)c(C2CCN(CC(=O)O)CC2)c(-c2cccc(Br)c2)c2ccc(C)nc21
Temperature: 100 °C
Reaction time: 15 h

Procedure:
To 370 mg of ethyl {4-[4-(3-bromophenyl)-1-ethyl-7-methyl-2-oxo-1,2-dihydro-1,8-naphthyridin-3-yl]piperidin-1-yl}acetate was added 5 ml of 6M hydrochloric acid, followed by stirring at 100° C. for 15 hours. After removal of the solvent, the resulting crude crystals were recrystallized from ethanol-acetonitrile to obtain 185 mg of {4-[4-(3-bromophenyl)-1-ethyl-7-methyl-2-oxo-1,2-dihydro-1,8-naphthyridin-3-yl]piperidin-1-yl}acetic acid monohydrochloride as colorless crystals.
Reaction SMILES: Cl[C:2]1[CH:7]=[N:6][CH:5]=[C:4]([O:8][CH2:9][CH2:10][C:11]2[N:12]=[C:13]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[O:14][C:15]=2[CH3:16])[N:3]=1.CC1OC(C2C=CC=CC=2)=NC=1CCO.[NH:38]1[CH2:43][CH2:42][NH:41][CH2:40][CH2:39]1.C([O-])([O-])=O.[K+].[K+]>>[CH3:16][C:15]1[O:14][C:13]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[N:12][C:11]=1[CH2:10][CH2:9][O:8][C:4]1[CH:5]=[N:6][CH:7]=[C:2]([N:38]2[CH2:43][CH2:42][NH:41][CH2:40][CH2:39]2)[N:3]=1
Reactant: Cc1oc(-c2ccccc2)nc1CCOc1cncc(Cl)n1
Reactant: C1CNCCN1
Agent: Cc1oc(-c2ccccc2)nc1CCO
Agent: O=C([O-])[O-]
Agent: [K+]
Product: Cc1oc(-c2ccccc2)nc1CCOc1cncc(N2CCNCC2)n1

Procedure:
The title compound was prepared according to the procedure of example 50, step 2, starting from 2-chloro-6-[2-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy]pyrazine [2.90 g, 9.18 mmol; obtained according to the procedure of example 50, step 1, starting from 2-(5-methyl-2-phenyloxazol-4-yl)ethanol], piperazine (2.37 g, 27.5 mmol) and K2CO3 (1.27 g, 9.19 mmol) with the exception that the final filtration through alumina was omitted. The yield of the of the title compound was 2.09 g (62%) which was obtained as a light yellow oil that solidified when refrigerated. Purity 100% (HPLC). MS m/z 365 (M)+. HRMS m/z calcd for C20H23N5O2 (M)+ 365.1852, found 365.1855.
Reaction SMILES: [H-].[Al+3].[Li+].[H-].[H-].[H-].[CH3:7][CH:8]1[CH2:16][C:15]2[C:10](=[C:11]([CH3:20])[CH:12]=[CH:13][C:14]=2[CH:17]([CH3:19])[CH3:18])[C:9]1=[O:21].[OH-].[Na+]>C(OCC)C>[CH3:7][CH:8]1[CH2:16][C:15]2[C:10](=[C:11]([CH3:20])[CH:12]=[CH:13][C:14]=2[CH:17]([CH3:18])[CH3:19])[CH:9]1[OH:21]
Reactant: Cc1ccc(C(C)C)c2c1C(=O)C(C)C2
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: CCOCC
Product: Cc1ccc(C(C)C)c2c1C(O)C(C)C2
Temperature: 25 °C
Reaction time: 1.5 h

Procedure:
In a 1-liter three-necked flask equipped with a 300-ml dropping funnel and a Dimroth condenser were charged 5.00 g (0.132 mol) of lithium aluminum hydride and 300 ml of diethyl ether, to which was dripped down at 0° C. over 1.5 hours about 50 g (0.25 mol) of 2,7-dimethyl-4-isopropyl-1-indanone diluted with 200 ml of diethyl ether. After stirring at room temperature for 30 minutes, the mixture was stirred under reflux for 1.5 hours. After completion of the reaction, 10 ml of ice water and 10 ml of aqueous sodium hydroxide solution were added at 0° C. and the resulting mixture was extracted with diethyl ether. The organic layer was washed with an aqueous sodium hydrogen carbonate solution and with saline and then dried over sodium sulfate. Sodium sulfate was removed by filtration and the solvent was distilled off under reduced pressure.
Reaction SMILES: [H-].[Na+].[Br:3][C:4]1[CH:5]=[C:6]([CH2:11][C:12]#[N:13])[CH:7]=[C:8]([Br:10])[CH:9]=1.Br[CH2:15][CH2:16]Br.O>CS(C)=O>[Br:3][C:4]1[CH:5]=[C:6]([C:11]2([C:12]#[N:13])[CH2:16][CH2:15]2)[CH:7]=[C:8]([Br:10])[CH:9]=1
Reactant: N#CCc1cc(Br)cc(Br)c1
Reactant: BrCCBr
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CS(C)=O
Product: N#CC1(c2cc(Br)cc(Br)c2)CC1
Temperature: 25 °C
Reaction time: 0.67 h
Yield: 83.3 %

Procedure:
Sodium hydride (1.601 g, 40.02 mmol) was added portionwise over 10 minutes to a solution of 2-(3,5-dibromophenyl)acetonitrile (5.0 g, 18.19 mmol) in DMSO (40 mL) at room temperature. The reaction was stirred at room temperature for 40 mins then cooled in an ice-bath whilst 1,2-dibromoethane (3.588 g, 1.646 mL, 19.10 mmol) was added dropwise. The reaction was then warmed to room temperature and stirred overnight. Water was added (100 mL) and mixture extracted with ethyl acetate/toluene (3×150 mL, 2:1). The organics were combined, washed with 1M HCl, water, and brine then dried over MgSO4, filtered and the solvent removed under reduced pressure. The crude product was purified on silica (Companion, 120 g) eluting with 1-20% EtOAc:Petrol ether to give 1-(3,5-dibromophenyl)cyclopropane-1-carbonitrile as a light yellow solid (4.56 g, 83%).
Reaction SMILES: Br[C:2]1[C:10]2[C:5](=[N:6][CH:7]=[C:8]([C:11]3[CH:12]=[C:13]([CH:26]=[CH:27][CH:28]=3)[C:14]([NH:16][C:17]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)([CH3:19])[CH3:18])=[O:15])[CH:9]=2)[O:4][C:3]=1[C:29]1[CH:34]=[CH:33][C:32]([F:35])=[CH:31][CH:30]=1.[CH3:36]B1OB(C)OB(C)O1.C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C.O.CCOC(C)=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:35][C:32]1[CH:33]=[CH:34][C:29]([C:3]2[O:4][C:5]3=[N:6][CH:7]=[C:8]([C:11]4[CH:12]=[C:13]([CH:26]=[CH:27][CH:28]=4)[C:14]([NH:16][C:17]([C:20]4[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=4)([CH3:19])[CH3:18])=[O:15])[CH:9]=[C:10]3[C:2]=2[CH3:36])=[CH:30][CH:31]=1
Reactant: CC(C)(NC(=O)c1cccc(-c2cnc3oc(-c4ccc(F)cc4)c(Br)c3c2)c1)c1ccccc1
Reactant: CB1OB(C)OB(C)O1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Solvent: O
Product: Cc1c(-c2ccc(F)cc2)oc2ncc(-c3cccc(C(=O)NC(C)(C)c4ccccc4)c3)cc12
Reaction time: 0.5 h
Yield: 84.2 %

Procedure:
Pd(Ph3P)4 (4.4 mg, 3.8 μmol) was added to a stirring solution of 3-(3-bromo-2-(4-fluorophenyl)furo[2,3-b]pyridin-5-yl)-N-(2-phenylpropan-2-yl)benzamide (20 mg, 0.038 mmol), trimethylboroxine (11 μL, 0.076 mmol), and Na2CO3 (12.0 mg, 0.11 mmol) in DMF (1.4 mL) and Water (0.14 mL) at room temperature. It was subjected to microwave irradiation: 180° C. for 30 min. The mixture was diluted with EtOAc and washed with sat NaHCO3, and sat NaCl. The organic phase was dried over Na2SO4, filtered and concentrated was purified on silica gel (Biotage, EtOAc/hexanes gradient, fraction collection at λ=254 nm) to give the expected product 3-(2-(4-fluorophenyl)-3-methylfuro[2,3-b]pyridin-5-yl)-N-(2-phenylpropan-2-yl)benzamide (15 mg, 0.032 mmol, 85% yield) by LCMS. LC-MS retention time: 1.87 min; m/z (MH+): 465. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Waters XBridge 5 u C18 4.6×50 mm column using a SPD-10AV UV-Vis detector at a detector wave length of 220 nM. The elution conditions employed a flow rate of 5 ml/min, a gradient of 100% solvent A/0% solvent B to 0% solvent A/100% solvent B, a gradient time of 2 min, a hold time of 1 min, and an analysis time of 3 min where solvent A was 5% acetonitrile/95% H2O/10 mM ammonium acetate and solvent B was 5% H2O/95% acetonitrile/10 mM ammonium acetate. MS data was determined using a Micromass Platform for LC in electrospray mode.
Reaction SMILES: [CH3:1][O:2][C:3]1[C:4]([NH:15][C:16](=[O:20])OCC)=[N:5][C:6]2[C:11]([N:12]=1)=[CH:10][C:9]([O:13][CH3:14])=[CH:8][CH:7]=2.[CH3:21][O:22][C:23]1[CH:24]=[C:25]([N:33]2[CH2:38][CH2:37][NH:36][CH2:35][CH2:34]2)[CH:26]=[C:27]([O:31][CH3:32])[C:28]=1[O:29][CH3:30]>>[CH3:1][O:2][C:3]1[C:4]([NH:15][C:16]([N:36]2[CH2:35][CH2:34][N:33]([C:25]3[CH:24]=[C:23]([O:22][CH3:21])[C:28]([O:29][CH3:30])=[C:27]([O:31][CH3:32])[CH:26]=3)[CH2:38][CH2:37]2)=[O:20])=[N:5][C:6]2[C:11]([N:12]=1)=[CH:10][C:9]([O:13][CH3:14])=[CH:8][CH:7]=2
Reactant: COc1cc(N2CCNCC2)cc(OC)c1OC
Reactant: CCOC(=O)Nc1nc2ccc(OC)cc2nc1OC
Product: COc1ccc2nc(NC(=O)N3CCN(c4cc(OC)c(OC)c(OC)c4)CC3)c(OC)nc2c1
Yield: 92 %

Procedure:
Ethyl N-(3,6-dimethoxyquinoxalin-2-yl)carbamate and 1-(3,4,5-trimethoxyphenyl)piperazine were reacted by the same way with the example 148 to obtain the titled compound (yield, 92%).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[S:10](=[O:15])(=[O:14])[N:11]([CH3:13])[CH3:12])[CH2:5]O.S(Cl)([Cl:18])=O>C(Cl)Cl.CCCCCC>[Br:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[S:10](=[O:15])(=[O:14])[N:11]([CH3:13])[CH3:12])[CH2:5][Cl:18]
Reactant: O=S(Cl)Cl
Reactant: CN(C)S(=O)(=O)c1ccc(CO)cc1Br
Solvent: CCCCCC
Solvent: ClCCl
Product: CN(C)S(=O)(=O)c1ccc(CCl)cc1Br
Temperature: 25 °C
Reaction time: 2 h
Yield: 99.4 %

Procedure:
To a solution of OBS02002 (5.0 g, 16.12 mmol) in anhydrous DCM (50 mL) was added thionyl chloride (1.76 mL, 24.18 mmol). The mixture was stirred at room temperature for 2 h and the volatiles removed in vacuo. The residue was re-dissolved and co-evaporated three times with DCM (3×20 mL) to give a yellow oil which solidified on standing. The solid was stirred in n-hexane, filtered and air-dried to give OBS02003 as an off-white solid (5.01 g, 95%). TLC [SiO2, EtOAc-n-hexane (1:1)] Rf=0.79; 1H-NMR (270 MHz, CDCl3)=3.05 (6H, s), 4.51 (2H, s), 7.32 (1H, dd, J=2.2, 8.4), 7.48 (1H, d, J=8.4), 7.62 (1H, d, J=2.2).
Reaction SMILES: Cl[CH2:2][C:3]1[C:4]([C:9]2[CH:14]=[C:13]([O:15][CH3:16])[C:12]([O:17][CH3:18])=[C:11]([O:19][CH3:20])[CH:10]=2)=[N:5][CH:6]=[CH:7][CH:8]=1.[NH:21]1[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]1>>[CH3:20][O:19][C:11]1[CH:10]=[C:9]([C:4]2[C:3]([CH2:2][N:21]3[CH2:26][CH2:25][N:24]([CH2:2][C:3]4[C:4]([C:9]5[CH:14]=[C:13]([O:15][CH3:16])[C:12]([O:17][CH3:18])=[C:11]([O:19][CH3:20])[CH:10]=5)=[N:5][CH:6]=[CH:7][CH:8]=4)[CH2:23][CH2:22]3)=[CH:8][CH:7]=[CH:6][N:5]=2)[CH:14]=[C:13]([O:15][CH3:16])[C:12]=1[O:17][CH3:18]
Reactant: COc1cc(-c2ncccc2CCl)cc(OC)c1OC
Reactant: C1CNCCN1
Product: COc1cc(-c2ncccc2CN2CCN(Cc3cccnc3-c3cc(OC)c(OC)c(OC)c3)CC2)cc(OC)c1OC

Procedure:
3-Chloromethyl-2-(3,4,5-trimethoxyphenyl) pyridine (241 mg) and piperazine (35 mg) were reacted in the same manner as in Example 1 to obtain the title compound as a free base.
Reaction SMILES: [CH2:1]([S:3][C:4]1[N:5]([C:17]2[CH:22]=[CH:21][C:20]([O:23][CH2:24][C:25]([F:28])([F:27])[F:26])=[CH:19][CH:18]=2)[C:6](=[O:16])[C:7]2[CH:13]=[CH:12][C:11]([O:14]C)=[N:10][C:8]=2[N:9]=1)[CH3:2].Cl.N1C=CC=CC=1.Cl>CN(C)C=O>[CH2:1]([S:3][C:4]1[N:5]([C:17]2[CH:22]=[CH:21][C:20]([O:23][CH2:24][C:25]([F:27])([F:28])[F:26])=[CH:19][CH:18]=2)[C:6](=[O:16])[C:7]2[CH:13]=[CH:12][C:11](=[O:14])[NH:10][C:8]=2[N:9]=1)[CH3:2]
Reactant: CCSc1nc2nc(OC)ccc2c(=O)n1-c1ccc(OCC(F)(F)F)cc1
Agent: Cl
Solvent: CN(C)C=O
Solvent: c1ccncc1
Product: CCSc1nc2[nH]c(=O)ccc2c(=O)n1-c1ccc(OCC(F)(F)F)cc1
Temperature: 120 °C
Reaction time: 0.25 h
Yield: 94.6 %

Procedure:
A mixture of 2-(ethylsulfanyl)-7-methoxy-3-[4-(2,2,2-trifluoroethoxy)phenyl]pyrido[2,3-d]pyrimidin-4(3H)-one (150 mg), pyridine hydrochloride (1156 mg) and N,N-dimethylformamide (1 ml) was stirred at 120° C. for 15 min. The reaction mixture was poured into 0.2M hydrochloric acid (10 ml), and the precipitated white solid was collected by filtration, and washed with water. The obtained solid was dissolved in tetrahydrofuran (5 ml), and the solution was diluted with ethyl acetate (70 ml), washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (137 mg) as a white solid.