Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: I[C:2]1[S:3][C:4]2[NH:5][C:6](=[O:15])[C:7]3[CH:8]=[CH:9][CH:10]=[CH:11][C:12]=3[C:13]=2[N:14]=1.CN(C=O)C.[CH3:21][N:22]([CH3:26])[CH2:23][C:24]#[CH:25]>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.[Cu]I.C(N(CC)CC)C>[CH3:21][N:22]([CH3:26])[CH2:23][C:24]#[C:25][C:2]1[S:3][C:4]2[NH:5][C:6](=[O:15])[C:7]3[CH:8]=[CH:9][CH:10]=[CH:11][C:12]=3[C:13]=2[N:14]=1
Reactant: C#CCN(C)C
Reactant: O=c1[nH]c2sc(I)nc2c2ccccc12
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Cu]I
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: CN(C)CC#Cc1nc2c([nH]c(=O)c3ccccc32)s1
Yield: 68 %

Procedure:
2-Iodo-1,3-thiazolo[5,4-c]isoquinolin-5(4H)-one (0.1 g, 0.3 mmol), DMF (10 ml), 1-dimethylamino-2-propyne (0.25 g, 3.05 mmol), (Ph3P)2PdCl2 (10 mg), CuI (1 mg), and triethylamine (1.2 ml) were stirred at room temperature for 4 hours. The solvent was removed under reduced pressure and the mixture was chromatographed on SiO2 gel, eluting, with dichloromethane/methanol (98/2), to produce the title compound. Yield: 68% yield.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:12][CH2:11][C@H:10]([CH2:13][NH:14][C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[CH2:9]2)=[C:4]([F:22])[CH:3]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[CH3:36][C:37]([CH3:39])=O>>[F:22][C:4]1[CH:3]=[C:2]([NH:1][CH:37]([CH3:39])[CH3:36])[CH:7]=[CH:6][C:5]=1[N:8]1[CH2:12][CH2:11][C@H:10]([CH2:13][NH:14][C:15](=[O:21])[O:16][C:17]([CH3:18])([CH3:19])[CH3:20])[CH2:9]1
Reactant: CC(C)=O
Reactant: CC(C)(C)OC(=O)NC[C@H]1CCN(c2ccc(N)cc2F)C1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Product: CC(C)Nc1ccc(N2CC[C@H](CNC(=O)OC(C)(C)C)C2)c(F)c1

Procedure:
tert-Butyl (R)-[1-(4-amino-2-fluorophenyl)pyrrolidin-3-yl]methylcarbamate was alkylated with acetone using triacetoxyborohydride as reducing agent by method N. This resulted in the product with the molecular weight of 351.47 (C19H30FN3O2); MS (ESI): 352 (M+H+).
Reaction SMILES: [Cl:1][C:2]1[C:9]([Cl:10])=[CH:8][CH:7]=[CH:6][C:3]=1[CH:4]=O.[O:11]=[C:12]([CH3:21])[CH2:13][C:14]([O:16][CH:17]1[CH2:20][O:19][CH2:18]1)=[O:15]>N1CCCCC1.C(O)(=O)CCCCC.C1C=CC=CC=1>[Cl:1][C:2]1[C:9]([Cl:10])=[CH:8][CH:7]=[CH:6][C:3]=1[CH:4]=[C:13]([C:12](=[O:11])[CH3:21])[C:14]([O:16][CH:17]1[CH2:20][O:19][CH2:18]1)=[O:15]
Reactant: CC(=O)CC(=O)OC1COC1
Reactant: O=Cc1cccc(Cl)c1Cl
Solvent: CCCCCC(=O)O
Solvent: c1ccccc1
Solvent: C1CCNCC1
Product: CC(=O)C(=Cc1cccc(Cl)c1Cl)C(=O)OC1COC1
Temperature: 25 °C
Yield: 121.1 %

Procedure:
A solution of 2,3-dichlorobenzaldehyde (1.33 g, 7.6 mmoles), 3-oxetanyl 3-oxobutanoate (1.2 g, 7.6 mmoles), piperidine (6 drops) and hexanoic acid (8 drops) in dry benzene (80 ml) was heated at reflux using a Dean and Stark apparatus. The solution was allowed to cool to room temperature and the solvent removed in vacuo to leave the sub-title compound as an oil 2.9 g.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:37])[CH2:5][CH2:6][CH2:7][O:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][O:21][C:22]2[CH:27]=[C:26]([OH:28])[CH:25]=[C:24]([Br:29])[CH:23]=2)[C:10]=1[CH2:30][CH2:31][C:32]([O:34][CH2:35][CH3:36])=[O:33])[CH3:2].C(=O)([O-])[O-].[K+].[K+].CN(C)C=O.I[CH2:50][CH3:51]>O.CC(C)=O>[CH2:1]([O:3][C:4](=[O:37])[CH2:5][CH2:6][CH2:7][O:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][O:21][C:22]2[CH:27]=[C:26]([O:28][CH2:50][CH3:51])[CH:25]=[C:24]([Br:29])[CH:23]=2)[C:10]=1[CH2:30][CH2:31][C:32]([O:34][CH2:35][CH3:36])=[O:33])[CH3:2]
Reactant: CCI
Reactant: CCOC(=O)CCCOc1cccc(CCCCCCOc2cc(O)cc(Br)c2)c1CCC(=O)OCC
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CC(C)=O
Solvent: O
Product: CCOC(=O)CCCOc1cccc(CCCCCCOc2cc(Br)cc(OCC)c2)c1CCC(=O)OCC
Temperature: 25 °C
Yield: 97.6 %

Procedure:
To a mixture of 4-[3-[6-(3-bromo-5-hydroxy-phenoxy)-hexyl]-2-(2-ethoxycarbonyl-ethyl)-phenoxy]-butyric acid ethyl ester (163 mg, 0.28 mmol) and potassium carbonate (117 mg, 0.84 mmol) were added dimethylformamide (4 mL), acetone (8 mL), and iodoethane (219 mg, 1.4 mmol) at room temperature. The resulting suspension was heated to reflux for 2 days. Then, the reaction mixture was cooled to room temperature and diluted with water (20 mL). The organic compound was extracted into ethyl acetate (2×25 mL) and the combined organic extracts were washed with water (50 mL) and brine solution (50 mL). The organic layers were dried over anhydrous magnesium sulfate and filtration of the drying agent and concentration of the solvent gave the crude product which was purified by using an ISCO 40 g column, eluting with 0-30% ethyl acetate in hexanes to afford 4-[3-[6-(3-bromo-5-ethoxy-phenoxy)-hexyl]-2-(2-ethoxycarbonyl-ethyl)-phenoxy]-butyric acid ethyl ester (166 mg, 98%) as a colorless oil: ES(+)-HRMS m/e calcd for C31H43BrO7 (M+H)+ 607.2265. found 607.2270.
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[CH:10]=[N:9][N:8]([CH3:11])[C:7]=1[C:12]([OH:14])=O)=[O:5])[CH3:2].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:39][O:40][C:41]1[CH:42]=[C:43]([C:47]2[N:56]=[C:50]3[CH:51]=[C:52]([NH2:55])[CH:53]=[CH:54][N:49]3[N:48]=2)[CH:44]=[CH:45][CH:46]=1.CCN(C(C)C)C(C)C>CN(C=O)C.O>[CH2:1]([O:3][C:4]([C:6]1[CH:10]=[N:9][N:8]([CH3:11])[C:7]=1[C:12](=[O:14])[NH:55][C:52]1[CH:53]=[CH:54][N:49]2[N:48]=[C:47]([C:43]3[CH:44]=[CH:45][CH:46]=[C:41]([O:40][CH3:39])[CH:42]=3)[N:56]=[C:50]2[CH:51]=1)=[O:5])[CH3:2]
Reactant: COc1cccc(-c2nc3cc(N)ccn3n2)c1
Reactant: CCOC(=O)c1cnn(C)c1C(=O)O
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: O
Solvent: CCN(C(C)C)C(C)C
Product: CCOC(=O)c1cnn(C)c1C(=O)Nc1ccn2nc(-c3cccc(OC)c3)nc2c1
Temperature: 25 °C
Reaction time: 16 h
Yield: 45.9 %

Procedure:
To a solution of 2-methyl-2H-pyrazole-3,4-dicarboxylic acid 4-ethyl ester (8.0 g, 40.4 mmol) in DMF (120 ml) were added HATU (34 g, 88.9 mmol), 2-(3-methoxy-phenyl)-[1,2,4]triazolo[1,5-a]pyridin-7-ylamine (10.6 g, 44.4 mmol) and DIPEA (30 ml, 161.1 mmol) at 0° C. The reaction mixture was stirred at 25° C. for 16 h. The reaction mixture was diluted with water. The resultant precipitated solid was filtered, washed with water, dried azeotropically with toluene followed by vacuum to yield 5-[2-(3-methoxy-phenyl)-[1,2,4]triazolo[1,5-a]pyridin-7-ylcarbamoyl]-1-methyl-1H-pyrazole-4-carboxylic acid ethyl ester as white solid (7.8 g, 56%). LC-MS: m/z=421.2 [M+H]+.
Reaction SMILES: [OH:1][C:2]1[C:11]([CH2:12]/[CH:13]=[CH:14]/[CH2:15]O)=[CH:10][C:9]([CH3:17])=[C:8]2[C:3]=1[CH:4]=[CH:5][C:6](=[O:18])[NH:7]2.B(F)(F)F.C(=O)(O)[O-].[Na+].O>ClCCCl>[CH3:17][C:9]1[CH:10]=[C:11]2[CH2:12][CH:13]([CH:14]=[CH2:15])[O:1][C:2]2=[C:3]2[C:8]=1[NH:7][C:6](=[O:18])[CH:5]=[CH:4]2
Reactant: Cc1cc(C/C=C/CO)c(O)c2ccc(=O)[nH]c12
Agent: FB(F)F
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCCl
Solvent: O
Product: C=CC1Cc2cc(C)c3[nH]c(=O)ccc3c2O1
Temperature: 60 °C
Reaction time: 5 h
Yield: 97.5 %

Procedure:
5-Hydroxy-6-(trans-4-hydroxy-2-butenyl)-8-methylcarbostyril (2.6 g) was suspended in 1,2-dichloroethane (50 ml). Boron trifluoride.ether complex (7.5 ml) was added to the suspension, and the mixture was stirred at 60° C. for 5 hours. After the reaction, saturated sodium bicarbonate (50 ml) was added thereto, followed by stirring at room temperature for 1.5 hours. Water was added thereto and extraction was performed with chloroform. The extract was dried and condensed under reduced pressure, and the residue was recrystallized from a solvent mixture of chloroform-ether. As a result, 2.35 g of 5-methyl-2,3,6,7-tetrahydro-2-vinylfuro[2,3-f]quinoline-7-one was obtained as pale brown powdery crystals (97.6%).
Reaction SMILES: C[O:2][C:3](=[O:22])[CH2:4][CH:5]1[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[C:12]2[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=2[N:6]1[C:19](=[O:21])[CH3:20].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>O1CCOCC1.O.[Li+].[OH-]>[C:19]([N:6]1[CH:5]([CH2:4][C:3]([OH:22])=[O:2])[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[C:12]2[CH:11]=[CH:10][CH:9]=[CH:8][C:7]1=2)(=[O:21])[CH3:20]
Reactant: COC(=O)CC1c2ccccc2-c2ccccc2N1C(C)=O
Agent: O=C(O)CC(O)(CC(=O)O)C(=O)O
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: C1COCCO1
Product: CC(=O)N1c2ccccc2-c2ccccc2C1CC(=O)O
Temperature: 25 °C
Reaction time: 4 h

Procedure:
To a solution of (5-acetyl-5,6-dihydro-phenanthridin-6-yl)-acetic acid methyl ester (210 mg, 0.71 mmol) dissolved in a mixture of dioxane (10 mL) and water (10 mL), LiOH×H2O (42 mg, 1 mmol) was added. The solution was allowed to stir at r.t. for 4 h. Citric acid (5% solution in water) was added and the mixture was extracted with ethyl acetate. The organic phase was washed with citric acid (2×), water (1×), and brine (1×). After drying over MgSO4, the solvent was removed in vacuo to give a colourless oil that solidified on standing ar r.t. Yield, 70%. (+)-ESI-MS: m/z=282 [M+H]+, 240, 222, 180.
Reaction SMILES: [CH3:1][C:2](=[CH2:6])[CH2:3][CH2:4][OH:5].[C:7]1(O)[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O>O1CCCC1>[CH3:6][C:2](=[CH2:1])[CH2:3][CH2:4][O:5][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1
Reactant: C=C(C)CCO
Reactant: Oc1ccccc1
Agent: CC(C)(C)OC(=O)N=NC(=O)OC(C)(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: C=C(C)CCOc1ccccc1
Temperature: 70 °C

Procedure:
To a stirred solution of 3-methyl-3-buten-1-ol (1.17 ml) in tetrahydrofuran (30 ml) were added sequentially phenol (1.32 g), triphenylphosphine (3.85 g) and di-tert-butyl azodicarboxylate (3.27 g). The mixture was heated at 70° C. overnight and then was concentrated in vacuo. The residue was purified by column chromatography (SiO2; gradient: heptane/EtOAc 100:0->70:30) to give (3-methyl-but-3-enyloxy)-benzene (2.06 g, quant.) as a colourless semi-solid which crystallized on standing.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[N:9]([C:17]([NH2:19])=[O:18])[C:10]3[C:15]([CH:16]=2)=[CH:14][CH:13]=[CH:12][CH:11]=3)[CH:5]=[CH:6][CH:7]=1.[CH2:20]([C:22]1[CH:23]=[C:24]([N:28]=[C:29]=[O:30])[CH:25]=[CH:26][CH:27]=1)[CH3:21]>C1COCC1.C(OCC)(=O)C>[CH2:20]([C:22]1[CH:23]=[C:24]([NH:28][C:29]([NH:1][C:2]2[CH:3]=[C:4]([C:8]3[N:9]([C:17]([NH2:19])=[O:18])[C:10]4[C:15]([CH:16]=3)=[CH:14][CH:13]=[CH:12][CH:11]=4)[CH:5]=[CH:6][CH:7]=2)=[O:30])[CH:25]=[CH:26][CH:27]=1)[CH3:21]
Reactant: NC(=O)n1c(-c2cccc(N)c2)cc2ccccc21
Reactant: CCc1cccc(N=C=O)c1
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: CCc1cccc(NC(=O)Nc2cccc(-c3cc4ccccc4n3C(N)=O)c2)c1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To the solution of 2-(3-aminophenyl)-1H-indole-1-carboxamide (50.2 mg, 0.2 mmol, 1 eq) in anhydrous THF (2 mL) was added 3-ethylphenyl isocyanate (29 μL, 1 eq) and the reaction solution was stirred at room temperature for one hour. It was then diluted with ethyl acetate, washed with aqueous ammonium chloride, saturated aqueous sodium bicarbonate, brine, and lastly dried with anhydrous sodium sulfate. The upper solution was decanted, concentrated and the oily residue was subject to a gradient column chromatography (from EtOAc-Hex 1:2 to MeOH-EtOAc 1:10). The product fractions were collected, concentrated, and the solid residue was triturated with EtOAc-Hex (1:1) to give 2-[3-({[(3-ethylphenyl)amino]carbonyl}amino)phenyl]-1H-indole-1-carboxamide as white solid upon filtration in amount of 32 mg.
Reaction SMILES: [CH3:1][C:2]1[C:6]2[C:7](=[O:18])[N:8]([CH2:11][CH2:12][N:13]3[CH2:17][CH2:16][CH2:15][CH2:14]3)[CH2:9][CH2:10][C:5]=2[NH:4][C:3]=1[CH:19]=O.[OH:21][CH2:22][CH2:23][C:24]1[CH:32]=[CH:31][CH:30]=[C:29]2[C:25]=1[CH2:26][C:27](=[O:33])[NH:28]2>>[OH:21][CH2:22][CH2:23][C:24]1[CH:32]=[CH:31][CH:30]=[C:29]2[C:25]=1[C:26](=[CH:19][C:3]1[NH:4][C:5]3[CH2:10][CH2:9][N:8]([CH2:11][CH2:12][N:13]4[CH2:14][CH2:15][CH2:16][CH2:17]4)[C:7](=[O:18])[C:6]=3[C:2]=1[CH3:1])[C:27](=[O:33])[NH:28]2
Reactant: O=C1Cc2c(CCO)cccc2N1
Reactant: Cc1c(C=O)[nH]c2c1C(=O)N(CCN1CCCC1)CC2
Product: Cc1c(C=C2C(=O)Nc3cccc(CCO)c32)[nH]c2c1C(=O)N(CCN1CCCC1)CC2
Yield: 30 %

Procedure:
The title compound was prepared under the same conditions as described in Example with 3-methyl-4-oxo-5-(2-pyrrolidin-1-yl-ethyl)-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridine-2-carbaldehyde and 4-(2-hydroxy-ethyl)-1,3-dihydro-indol-2-one (prepared according to US2004186160) as starting materials to give 2-[4-(2-hydroxy-ethyl)-2-oxo-1,2-dihydro-indol-3-ylidenemethyl]-3-methyl-5-(2-pyrrolidin-1-yl-ethyl)-1,5,6,7-tetrahydro-pyrrolo[3,2-c]pyridin-4-one (30 mg, 30.0%) as a yellow solid.
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH3:11].[CH3:12][S:13](=[S:16])([O-:15])=[O:14].[Na+].CN(C=O)C>O>[CH3:12][S:13](=[S:16])([O:15][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH3:11])=[O:14]
Reactant: CS(=O)([O-])=S
Reactant: CCCCCCCCCCBr
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: CCCCCCCCCCOS(C)(=O)=S
Temperature: 60 °C
Yield: 94 %

Procedure:
The mixture of 1-bromodecane (2.095 g, 0.00947 mol), sodium methanethiosulfonate and dry DMF (6 mL) was heated at 60° C. for 2 hr. At room temperature, water (15 mL) was added and the mixture was extracted with ether (3×30 mL). The ether extracts were washed with brine, dried, concentrated and the residue was subjected to flash column chromatography on silica gel with EtOAc-hexanes (1:4) to afford a white solid (2.063 g, 94%). It was recrystallized from 95% EtOH. mp: 28.0-29.5° C. IR (CDCl3 cast): 2954 (m), 2921 (st), 2852 (st), 1469 (m), 1305 (st), 1128 (st), 965 (m), 758 (m) and 720 cm−1 (m); 1H NMR (200 MHz, CDCl3): δ 3.32 (s, 3H, CH3SO2S), 3.17 (t, J=7.4 Hz, 2H, SCH2CH2), 1.77 (m, 2H, SCH2CH2), 1.50-1.20 (m, 14H, —(CH2)7—), 0.88 (m, 3H, CH2CH3); 13C NMR (50 MHz, CDCl3): δ 50.64, 36.49, 31.84, 29.45 (two carbons), 29.37, 29.23, 28.94, 28.57, 22.64, 14.08.
Reaction SMILES: [CH:1]1([NH:6][C:7]2[N:12]=[C:11]([C:13]3[N:17]4[CH:18]=[CH:19][CH:20]=[C:21]([N:22]5[CH2:27][CH2:26][O:25][CH2:24][CH2:23]5)[C:16]4=[N:15][C:14]=3[C:28]3[CH:35]=[CH:34][C:31]([C:32]#[N:33])=[CH:30][CH:29]=3)[CH:10]=[CH:9][N:8]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[OH-:36].[NH4+].OO>CO.O1CCCC1>[CH:1]1([NH:6][C:7]2[N:12]=[C:11]([C:13]3[N:17]4[CH:18]=[CH:19][CH:20]=[C:21]([N:22]5[CH2:27][CH2:26][O:25][CH2:24][CH2:23]5)[C:16]4=[N:15][C:14]=3[C:28]3[CH:29]=[CH:30][C:31]([C:32]([NH2:33])=[O:36])=[CH:34][CH:35]=3)[CH:10]=[CH:9][N:8]=2)[CH2:2][CH2:3][CH2:4][CH2:5]1
Reactant: [OH-]
Reactant: N#Cc1ccc(-c2nc3c(N4CCOCC4)cccn3c2-c2ccnc(NC3CCCC3)n2)cc1
Agent: OO
Agent: [NH4+]
Solvent: C1CCOC1
Solvent: CO
Product: NC(=O)c1ccc(-c2nc3c(N4CCOCC4)cccn3c2-c2ccnc(NC3CCCC3)n2)cc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 99 %

Procedure:
To a cold (0° C.) solution of 4-[3-[2-(cyclopentylamino)-4-pyrimidinyl]-8-(4-morpholinyl)imidazo[1,2-α]pyridin-2-yl]benzonitrile (16 mg, 0.03 mmol) in methanol (2 mL) and tetrahydrofuran (2 mL) was added concentrated ammonium hydroxide (1 mL, 28%) followed by hydrogen peroxide (0.1 mL, 30%). The cold bath was removed and the mixture was stirred at room temperature for 2 hours at which time an additional 0.1 mL of 30% hydrogen peroxide was added. After an additional 14 hours, the reaction was quenched by the addition of saturated aqueous sodium thiosulfate. Ether was added and the layers separated. The organic layer was washed with brine. The aqueous layer was extracted with ether and the combined organics were dried over magnesium sulfate. Filtration and concentration followed by flash chromatography (3% to 10% methanol in dichloromethane) provided 4-[3-[2-(cyclopentylamino)-4-pyrimidinyl]-8-(4-morpholinyl)imidazo[1,2-α]pyridin-2-yl]benzamide (17 mg, 99%) as a white solid. 1H NMR (CDCl3): δ 9.03 (broad, 1H), 8.15 (d, 1H), 7.89–7.82 (m, 4H), 6.85 (t, 1H), 6.64 (d, 1H), 6.44 (d, 1H), 6.22–5.79 (broad, 2H), 5.36 (m, 1H), 4.37 (m, 1H), 4.02 (m, 4H), 3.61 (m, 4H), 2.20–2.11 (m, 2H), 1.84–1.57 (m, 6H); MS m/z 484 (M+1).
Reaction SMILES: Cl[C:2]1[O:3][C:4]([C:7]2[N:12]=[C:11]([NH:13][C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][N:15]=3)[CH:10]=[CH:9][CH:8]=2)=[CH:5][N:6]=1.[S:21]1[CH:25]=[CH:24][C:23](B(O)O)=[CH:22]1.C([O-])([O-])=O.[K+].[K+]>C1COCC1.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>[Cl:20][C:17]1[CH:18]=[CH:19][C:14]([NH:13][C:11]2[CH:10]=[CH:9][CH:8]=[C:7]([C:4]3[O:3][C:2]([C:23]4[CH:24]=[CH:25][S:21][CH:22]=4)=[N:6][CH:5]=3)[N:12]=2)=[N:15][CH:16]=1
Reactant: Clc1ccc(Nc2cccc(-c3cnc(Cl)o3)n2)nc1
Reactant: OB(O)c1ccsc1
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: [K+]
Solvent: C1CCOC1
Solvent: O
Product: Clc1ccc(Nc2cccc(-c3cnc(-c4ccsc4)o3)n2)nc1
Temperature: 100 °C
Yield: 88.7 %

Procedure:
A solution of [6-(2-chloro-oxazol-5-yl)-pyridin-2-yl]-(5-chloro-pyridin-2-yl)-amine (50 mg, 0.162 mmol) in THF (4 ml) and water (2 ml) was treated with 3-thiopheneboronic acid (25 mg, 0.195 mmol), Pd(PPh3)4 (19 mg, 0.0162 mmol) and K2CO3 (50 mg, 0.358 mmol) before heating to 100° C. for 60 h. The cooled mixture was treated with water and extracted with DCM. The combined organics were dried over MgSO4, filtered and evaporated under reduced pressure before purification by column chromatography on SiO2, eluting with 1% EtOH in DCM to afford the title compound as an off-white solid (51 mg, 89%). 1H NMR (400 MHz, DMSO-d6) δ 10.05 (s, 1H), 8.33-8.31 (m, 1H), 8.28 (d, J=2.5 Hz, 1H), 8.15 (d, J=9.0 Hz, 1H), 7.89 (dd, J=9.0, 2.7 Hz, 1H), 7.85 (s, 1H), 7.83-7.77 (m, 2H), 7.69-7.65 (m, 1H), 7.49 (d, J=8.3 Hz, 1H), 7.40 (d, J=7.4 Hz, 1H). (ESI+) m/z 355 (M+H)+. Retention time=4.28 mins (method 1).
Reaction SMILES: C([O:5][C:6](=[O:19])[CH2:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]#[N:16])=[CH:11][C:10]=1[C:17]#[CH:18])(C)(C)C.[CH2:20]([S:27]([C:30]1[CH:35]=[CH:34][C:33]([CH3:36])=[C:32](Br)[CH:31]=1)(=[O:29])=[O:28])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>>[CH2:20]([S:27]([C:30]1[CH:35]=[CH:34][C:33]([CH3:36])=[C:32]([C:18]#[C:17][C:10]2[CH:11]=[C:12]([C:15]#[N:16])[CH:13]=[CH:14][C:9]=2[O:8][CH2:7][C:6]([OH:5])=[O:19])[CH:31]=1)(=[O:29])=[O:28])[C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1
Reactant: C#Cc1cc(C#N)ccc1OCC(=O)OC(C)(C)C
Reactant: Cc1ccc(S(=O)(=O)Cc2ccccc2)cc1Br
Product: Cc1ccc(S(=O)(=O)Cc2ccccc2)cc1C#Cc1cc(C#N)ccc1OCC(=O)O

Procedure:
Following the general method as outlined in Example 37, starting from tert-butyl(4-cyano-2-ethynyl phenoxy)acetate (Intermediate 46) and 4-(benzylsulfonyl)-2-bromo-1-methylbenzene (Intermediate 69), the title compound was obtained as a yellow solid.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:7](=O)[O:6][CH:5]2O.[NH2:13][NH2:14]>>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:7](=[O:6])[NH:14][N:13]=[CH:5]2
Reactant: O=C1OC(O)c2cc(Br)ccc21
Reactant: NN
Product: O=c1[nH]ncc2cc(Br)ccc12

Procedure:
5-Bromo-3-hydroxyphthalide is reacted in alcoholic solution with hydrazine to give 6-bromophthalazin-1(2H)-one which in turn is reacted with the appropriate (dialkylamino)alkylhalide in a polar solvent such as DMSO in the presence of a base such as KOH to give the 2-(dialkylaminoalkyl)-6-bromophthalazin-1(2H)-one. The styryl group is then attached by reacting the 6-bromo-2-substituted-phthalazin-1(2H)-one with styrene or 4-methoxystyrene in solvents such as DMSO or acetonitrile or mixtures thereof, in the presence of the reagents tri(o-tolyl)phosphine and palladium acetate to give the 6-[2-(phenyl or 4-methoxyphenyl)ethenyl]-2-[(dialkylamino)-alkyl]phthalazin-1(2H)-one. Specific methods for preparing the compounds of this invention are disclosed in the examples.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:11]=[C:10]2[C:6]([C:7]([C:12](=[O:16])[CH:13]([CH3:15])[CH3:14])=[N:8][NH:9]2)=[CH:5][CH:4]=1.Br[CH2:18][C:19]([O:21][CH2:22][CH3:23])=[O:20].CCOC(C)=O>CN(C=O)C.C(=O)([O-])[O-].[Cs+].[Cs+]>[C:12]([C:7]1[C:6]2[C:10](=[CH:11][C:3]([O:2][CH3:1])=[CH:4][CH:5]=2)[N:9]([CH2:18][C:19]([O:21][CH2:22][CH3:23])=[O:20])[N:8]=1)(=[O:16])[CH:13]([CH3:14])[CH3:15]
Reactant: CCOC(=O)CBr
Reactant: COc1ccc2c(C(=O)C(C)C)n[nH]c2c1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CCOC(=O)Cn1nc(C(=O)C(C)C)c2ccc(OC)cc21
Temperature: 25 °C
Reaction time: 8 h

Procedure:
Dissolve 5.456 g of 1-(6-methoxy-1H-indazol-3-yl)-2-methylpropan-1-one in 100 mL anhydrous DMF. Weigh in 8.96 g cesium carbonate followed by 4.593 g ethyl bromoacetate. The resulting mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure. Partition the residue between EtOAc and water. Extract the aqueous layer with EtOAc several times. The combined organic extract was washed with water (3×) and saturated brine, dried over anhydrous Na2SO4, and evaporated to give the crude product. The title compound was obtained by recrystallization from 40 mL 4:1 hexanes and EtOAc. 1H NMR (CDCl3, 500 MHz) δ 8.26 (d, 8.9 Hz, 1H), 7.00 (dd, 2.1 & 9.0 Hz, 1H), 6.685 (d, 2.1 Hz, 1H), 5.17 (s, 2H), 4.28 (q, 7.1 Hz, 2H), 3.90 (s, 3H), 3.87 (heptet, 6.9 Hz, 1H), 1.29 (t, 7.1 Hz, 3H), 1.28 (d, 6.8 Hz, 6H). LC-MS: 3.51 min. (m/Z=305.1, 327.0).
Reaction SMILES: [OH:1][C@H:2]([C:13]1[CH:22]=[CH:21][C:16]2[C:17](=[O:20])[O:18][CH2:19][C:15]=2[C:14]=1[CH3:23])[CH2:3][N:4]1[CH:9]2[CH2:10][NH:11][CH2:12][CH:5]1[CH2:6][O:7][CH2:8]2.[CH3:24][C@@H:25]1[CH2:34][C:33]2[C:28](=[CH:29][CH:30]=[C:31]([CH2:35][CH:36]=O)[CH:32]=2)[C:27](=[O:38])[O:26]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[OH:1][C@H:2]([C:13]1[C:14]([CH3:23])=[C:15]2[C:16](=[CH:21][CH:22]=1)[C:17](=[O:20])[O:18][CH2:19]2)[CH2:3][N:4]1[CH:9]2[CH2:10][N:11]([CH2:36][CH2:35][C:31]3[CH:32]=[C:33]4[C:28](=[CH:29][CH:30]=3)[C:27](=[O:38])[O:26][C@H:25]([CH3:24])[CH2:34]4)[CH2:12][CH:5]1[CH2:6][O:7][CH2:8]2
Reactant: C[C@@H]1Cc2cc(CC=O)ccc2C(=O)O1
Reactant: Cc1c([C@@H](O)CN2C3CNCC2COC3)ccc2c1COC2=O
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: ClCCCl
Product: Cc1c([C@@H](O)CN2C3COCC2CN(CCc2ccc4c(c2)C[C@@H](C)OC4=O)C3)ccc2c1COC2=O
Temperature: 25 °C
Reaction time: 1 h

Procedure:
A solution of 5-[(1R)-1-hydroxy-2-(3-oxa-7,9-diazabicyclo[3.3.1]non-9-yl)ethyl]-4-methyl-2-benzofuran-1(3H)-one (INTERMEDIATE 17) (60 mg, 0.19 mmol) and (R)-2-(3-Methyl-1-oxoisochroman-6-yl)acetaldehyde (INTERMEDIATE 21) (39 mg, 0.19 mmol) in 1,2-dichloroethane (5 mL) was treated with sodium triacetoxyborohydride (120 mg, 0.57 mmol) and stirred at room temperature for 1 hour. The reaction mixture was concentrated and the residue was purified by preparative TLC eluting with 5% (10% NH4OH in MeOH)/95% DCM, followed by a second preparative TLC iteration eluting with 5% (10% NH4OH in MeOH)/95% chloroform (eluted twice) to provide (R)-6-(2-(9-((R)-2-hydroxy-2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)ethyl)-3-oxa-7,9-diazabicyclo[3.3.1]nonan-7-yl)ethyl)-3-methylisochroman-1-one.
Reaction SMILES: Cl.[NH2:2][C@H:3]([C:14]([O:16][CH3:17])=[O:15])[CH2:4][C:5]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[NH:7][CH:6]=1.C(N(CC)CC)C.[CH:25]([C:28]1[CH:38]=[CH:37][C:31]([CH:32]=[CH:33][C:34](O)=[O:35])=[CH:30][CH:29]=1)([CH3:27])[CH3:26].CCN=C=NCCCN(C)C.Cl>C(Cl)Cl>[CH:25]([C:28]1[CH:29]=[CH:30][C:31]([CH:32]=[CH:33][C:34]([NH:2][C@H:3]([C:14]([O:16][CH3:17])=[O:15])[CH2:4][C:5]2[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[NH:7][CH:6]=2)=[O:35])=[CH:37][CH:38]=1)([CH3:27])[CH3:26]
Reactant: CC(C)c1ccc(C=CC(=O)O)cc1
Reactant: COC(=O)[C@@H](N)Cc1c[nH]c2ccccc12
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: COC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)C=Cc1ccc(C(C)C)cc1
Yield: 97.8 %

Procedure:
The same procedures as in Example 146 were carried out from methyl L-tryptophanate hydrochloride (3.0 g), triethylamine (2.0 mL), 4-i-propylcinnamic acid (2.7 g), WSC.HCl (2.7 g), and methylene chloride (80 mL), to give the captioned compound (4.5 g, 98%) as an oily product.