Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(O[C:6]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[CH:20]=[N:19][C:18](Br)=[CH:17][N:16]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.[C:22]([C:24]1[CH:29]=[CH:28][C:27](B(O)O)=[CH:26][CH:25]=1)#[N:23]>>[CH:6]1([N:8]2[CH2:9][CH2:10][CH:11]([O:14][C:15]3[CH:20]=[N:19][C:18]([C:27]4[CH:28]=[CH:29][C:24]([C:22]#[N:23])=[CH:25][CH:26]=4)=[CH:17][N:16]=3)[CH2:12][CH2:13]2)[CH2:12][CH2:11][CH2:10][CH2:9]1
Reactant: N#Cc1ccc(B(O)O)cc1
Reactant: CC(C)(C)OC(=O)N1CCC(Oc2cnc(Br)cn2)CC1
Product: N#Cc1ccc(-c2cnc(OC3CCN(C4CCCC4)CC3)cn2)cc1

Procedure:
According to the same method as in Example 1-2), 3), 4) but using 2-(1-t-butoxycabonylpiperidin-4-yloxy)-5-bromopyrazine and 4-cyanophenylboronic acid, the entitled compound was obtained.
Reaction SMILES: [CH3:1][C:2]([OH:11])([CH2:5][CH2:6][CH:7]([CH3:10])[CH2:8][CH3:9])[C:3]#[CH:4].[H][H]>CO.[Pd].[Zn]>[CH3:1][C:2]([OH:11])([CH2:5][CH2:6][CH:7]([CH3:10])[CH2:8][CH3:9])[CH:3]=[CH2:4]
Reactant: C#CC(C)(O)CCC(C)CC
Reactant: [H][H]
Agent: [Pd]
Agent: [Zn]
Solvent: CO
Product: C=CC(C)(O)CCC(C)CC
Reaction time: 6 h

Procedure:
154 g (1 mole) of 3,6-dimethyl-oct-1-yn-3ol are dissolved in 100 ml of methanol, 1 g of an 0.1% strength palladium/calcium carbonate catalyst, which has been poisoned with zinc ions, is added, and hydrogen is passed in at 20° C. under atmospheric pressure. The hydrogenation is complete in 6 hours, when about 24 liters of hydrogen have been absorbed.
Reaction SMILES: [Si]([O:8][CH:9]([C:11]1[CH:12]=[CH:13][C:14]([C:17]2[NH:18][C:19]([CH:23]([C:31]3[CH:36]=[CH:35][C:34]([S:37]([CH:40]4[CH2:42][CH2:41]4)(=[O:39])=[O:38])=[CH:33][CH:32]=3)[CH2:24][CH:25]3[CH2:30][CH2:29][O:28][CH2:27][CH2:26]3)=[CH:20][C:21]=2[CH3:22])=[N:15][CH:16]=1)[CH3:10])(C(C)(C)C)(C)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>O1CCCC1.C(OCC)(=O)C>[CH:40]1([S:37]([C:34]2[CH:33]=[CH:32][C:31]([CH:23]([C:19]3[NH:18][C:17]([C:14]4[N:15]=[CH:16][C:11]([CH:9]([OH:8])[CH3:10])=[CH:12][CH:13]=4)=[C:21]([CH3:22])[CH:20]=3)[CH2:24][CH:25]3[CH2:26][CH2:27][O:28][CH2:29][CH2:30]3)=[CH:36][CH:35]=2)(=[O:39])=[O:38])[CH2:42][CH2:41]1
Reactant: Cc1cc(C(CC2CCOCC2)c2ccc(S(=O)(=O)C3CC3)cc2)[nH]c1-c1ccc(C(C)O[Si](C)(C)C(C)(C)C)cn1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: Cc1cc(C(CC2CCOCC2)c2ccc(S(=O)(=O)C3CC3)cc2)[nH]c1-c1ccc(C(C)O)cn1
Temperature: 25 °C
Reaction time: 8 h
Yield: 78.6 %

Procedure:
To a solution (5 mL) of 5-(1-{[tert-butyl(dimethyl)silyl]oxy}ethyl)-2-(5-{1-[4-(cyclopropylsulfonyl)phenyl]-2-(tetrahydro-2H-pyran-4-yl)ethyl}-3-methyl-1H-pyrrol-2-yl)pyridine (130 mg) in tetrahydrofuran (5 mL) was added tetrabutylammonium fluoride (1M tetrahydrofuran solution, 256 μL), and the mixture was stirred overnight at room temperature. The reaction mixture was diluted with ethyl acetate and washed with water. The ethyl acetate layer was washed with saturated aqueous sodium hydrogen carbonate and saturated brine, dried (MgSO4) and concentrated. The residue was subjected to silica gel column chromatography, and the title compound (83.0 mg, yield 79%) was obtained as a pale-yellow amorphous solid from a fraction eluted with ethyl acetate-hexane (3:1, volume ratio). MS: 495 (MH+).
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:12][N:11]=[C:10]([CH3:13])[C:9]=2[NH:14][C:15]2[O:16][C:17]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)=[N:18][N:19]=2)=[CH:4][CH:3]=1.[CH2:26]([O:28][C:29]([CH2:31][CH2:32][C:33]1[CH:38]=[CH:37][C:36](B(O)O)=[CH:35][CH:34]=1)=[O:30])[CH3:27]>>[CH2:26]([O:28][C:29](=[O:30])[CH2:31][CH2:32][C:33]1[CH:38]=[CH:37][C:36]([C:2]2[CH:3]=[CH:4][C:5]([C:8]3[O:12][N:11]=[C:10]([CH3:13])[C:9]=3[NH:14][C:15]3[O:16][C:17]([C:20]4[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=4)=[N:18][N:19]=3)=[CH:6][CH:7]=2)=[CH:35][CH:34]=1)[CH3:27]
Reactant: Cc1noc(-c2ccc(Br)cc2)c1Nc1nnc(-c2ccccc2)o1
Reactant: CCOC(=O)CCc1ccc(B(O)O)cc1
Product: CCOC(=O)CCc1ccc(-c2ccc(-c3onc(C)c3Nc3nnc(-c4ccccc4)o3)cc2)cc1

Procedure:
Prepared according to the procedure described in Example 42, Step 2, using [5-(4-bromo-phenyl)-3-methyl-isoxazol-4-yl]-(5-phenyl-[1,3,4]oxadiazol-2-yl)-amine and [4-(2-ethoxycarbonylethyl)phenyl]boronic acid.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[F:10])[CH2:5][OH:6]>C(Cl)Cl>[Br:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[F:10])[CH:5]=[O:6]
Reactant: OCc1ccc(F)c(Br)c1
Solvent: ClCCl
Product: O=Cc1ccc(F)c(Br)c1
Reaction time: 1 h
Yield: 85.4 %

Procedure:
A solution of 45.9 g (0.225 mol) of 3-bromo-4-fluoro-benzyl alcohol in 45 ml of methylene chloride was added dropwise to a suspension of 78 g of pyridine/CrO3 /HCl in 450 ml of methylene chloride. During this addition, the temperature of the mixture rose to about 40° C. The mixture was then subsequently stirred for 1 hour, the organic phase was decanted from the chromium salts and the solvent was distilled off in vacuo. The residue was distilled. 39 g (86% of theory) of 3-bromo-4-fluoro-benzaldehyde with a boiling point of 63°-65° C./0.3 mm Hg were thus obtained.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([C:9](=O)[CH2:10][C:11](=O)[C:12]([F:15])([F:14])[F:13])[CH:5]=[CH:6][C:7]=1[F:8].[NH2:18][C:19]1[C:23]([C:24]#[N:25])=[CH:22][NH:21][N:20]=1>>[F:1][C:2]1[CH:3]=[C:4]([C:9]2[CH:10]=[C:11]([C:12]([F:15])([F:14])[F:13])[N:20]3[N:21]=[CH:22][C:23]([C:24]#[N:25])=[C:19]3[N:18]=2)[CH:5]=[CH:6][C:7]=1[F:8]
Reactant: O=C(CC(=O)C(F)(F)F)c1ccc(F)c(F)c1
Reactant: N#Cc1c[nH]nc1N
Product: N#Cc1cnn2c(C(F)(F)F)cc(-c3ccc(F)c(F)c3)nc12
Yield: 42.3 %

Procedure:
Reaction of 1-(3,4-difluoro-phenyl)-4,4,4-trifluoro-butane-1,3-dione (252 mg, 1.0 mmol), prepared from commercially available 3,4-difluoro-acetophenone according to general procedure A, and 3-amino-4-cyano-pyrazole (108 mg, 1.0 mmol) according to general procedure B yielded the title compound as a light yellow solid (137 mg, 42%).
Reaction SMILES: [C:1]([C:9]1[CH:17]=[CH:16][CH:15]=[CH:14][C:10]=1[C:11]([OH:13])=O)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:18]([O:22][C:23](=[O:29])[C@@H:24]1[CH2:28][CH2:27][CH2:26][NH:25]1)([CH3:21])([CH3:20])[CH3:19].O.ON1C2C=CC=CC=2N=N1.C1CCC(N=C=NC2CCCCC2)CC1>C(Cl)Cl>[CH3:21][C:18]([O:22][C:23](=[O:29])[C@@H:24]1[CH2:28][CH2:27][CH2:26][N:25]1[C:11](=[O:13])[C:10]1[CH:14]=[CH:15][CH:16]=[CH:17][C:9]=1[C:1](=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)([CH3:19])[CH3:20]
Reactant: O=C(O)c1ccccc1C(=O)c1ccccc1
Reactant: CC(C)(C)OC(=O)[C@@H]1CCCN1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: On1nnc2ccccc21
Solvent: O
Solvent: ClCCl
Product: CC(C)(C)OC(=O)[C@@H]1CCCN1C(=O)c1ccccc1C(=O)c1ccccc1

Procedure:
6.78 g (30mmol) of o-benzoylbenzoic acid, 5.13 g (30 mmol) of L-proline t-butyl ester, 4.05 g (30 mmol) of 1-hydroxybenzotriazole hydrate and 6.18 g (30 mmol) of DCC in 100 ml methylene chloride were reacted in the manner described in Example 25 for the coupling of o-benzoylbenzoic acid with L-proline t-butyl ester. A standard work-up as described in Example 25 afforded a viscous gum which was purified by flash chromatography on silica gel with 40:1/methylene chloride:methanol as eluant to give an amorphous solid. The isolated yield of the title compound was 8.6 g (76%). TLC (90:10/CH2Cl2 :MeOH): Rf =0.80. 1H NMR (CDCl3) δ: 7.30-7.80(m,9H,); 4.06-4.38(m,1H); 3.36-3.65(m,2H); 1.78-2.32(m,4H); 1.32(s),1.43(s,9H). I.R. (KBr): 1595, 1627, 1661, 1733 cm-1. Low Resolution Mass Spectrum: 380 (p+1). Standard Combustion Analysis Calculated: C,72.80; H,6.64; N,3.69. Found: C,72.37; H,6.59; N,3.76.
Reaction SMILES: [CH3:1][C:2]1([CH3:13])[C:10]2[C:5](=[CH:6][C:7]([CH3:11])=[CH:8][CH:9]=2)[C:4](=[O:12])[CH2:3]1.[CH3:14][CH:15](O)[CH:16]=[CH2:17].C1(C)C=CC(S(O)(=O)=O)=CC=1.O>COC(OC)(C)C>[CH2:14]([CH:3]1[C:2]([CH3:13])([CH3:1])[C:10]2[C:5](=[CH:6][C:7]([CH3:11])=[CH:8][CH:9]=2)[C:4]1=[O:12])[CH:15]=[CH:16][CH3:17]
Reactant: C=CC(C)O
Reactant: Cc1ccc2c(c1)C(=O)CC2(C)C
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: COC(C)(C)OC
Solvent: O
Product: CC=CCC1C(=O)c2cc(C)ccc2C1(C)C
Yield: 51 %

Procedure:
A solution of 18.9 g of 3,3,6-trimethyl-1-indanone, 22.4 ml of 3-buten-2-ol and 300 mg of p-toluenesulfonic acid in 200 ml of 2,2-dimethoxy-propane was boiled under reflux for 64 hours on a water separator filled with molecular sieve (0.4 nm, 2 mm pearl shaped). The reaction mixture was subsequently concentrated in a vacuum and purified by column chromatography on silica gel (hexane/ethyl acetate 6:1). In addition to 4.5 g of educt, there were obtained 12.7 g (51%) of (RS)-2-(2-buten-1-yl)-3,3,6-trimethyl-1-indanone as a yellow oil
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([NH:15][C:16]2[C:25]3[C:20](=[CH:21][CH:22]=[C:23]([C:26]4[N:30]([CH3:31])[C:29]([CH:32]=O)=[CH:28][N:27]=4)[CH:24]=3)[N:19]=[CH:18][N:17]=2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(O)(=O)C.[NH:38]1[CH2:45][CH2:44][CH2:43][C@H:39]1[C:40]([NH2:42])=[O:41].C(O[BH3-])(=O)C.[Na+]>ClCCl>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([NH:15][C:16]2[C:25]3[C:20](=[CH:21][CH:22]=[C:23]([C:26]4[N:30]([CH3:31])[C:29]([CH2:32][N:38]5[CH2:45][CH2:44][CH2:43][C@H:39]5[C:40]([NH2:42])=[O:41])=[CH:28][N:27]=4)[CH:24]=3)[N:19]=[CH:18][N:17]=2)=[CH:11][CH:10]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: NC(=O)[C@@H]1CCCN1
Reactant: Cn1c(C=O)cnc1-c1ccc2ncnc(Nc3ccc(OCc4ccccc4)cc3)c2c1
Agent: [BH3-]OC(C)=O
Agent: [Na+]
Solvent: CC(=O)O
Solvent: ClCCl
Product: Cn1c(CN2CCC[C@H]2C(N)=O)cnc1-c1ccc2ncnc(Nc3ccc(OCc4ccccc4)cc3)c2c1
Temperature: 20 °C
Reaction time: 0.75 h

Procedure:
2-(4-(4-Benzyloxy-phenylamino)-quinazolin-6-yl)-3-methyl-3H-imidazole-4-carbaldehyde was dissolved in dichloromethane (5 ml) containing glacial acetic acid (0.03 ml). L-prolinamide (0.028 g) was added and the mixture stirred at 20° C. for 0.75 hours. Sodium acetoxyborohydride (0.08 g) was added and the reaction stirred at 20° C. for 18 hours. The mixture was partitioned between 2N sodium carbonate and ethyl acetate, the organic phase was dried over magnesium sulphate and concentrated in vacuo. Chromatography on silica gave the title compound (0.008 g) as a yellow solid; tlc (SiO2, CH2Cl2:EtOH:NH3, 100:8:1) Rf 0.18; m/z (M+1)30 534.
Reaction SMILES: [CH3:1][C:2]([CH3:34])([CH3:33])[CH2:3][C:4]([NH:6][C:7]1[C:8]([CH3:32])=[C:9]([CH3:31])[C:10]2[O:14][CH2:13][CH:12]([C:15]3[CH:20]=[CH:19][C:18]([CH:21]([CH3:28])[CH2:22][C:23](OCC)=[O:24])=[CH:17][CH:16]=3)[C:11]=2[C:29]=1[CH3:30])=[O:5]>C(OCC)(=O)C.CCCCCC>[OH:24][CH2:23][CH2:22][CH:21]([C:18]1[CH:19]=[CH:20][C:15]([CH:12]2[C:11]3[C:29]([CH3:30])=[C:7]([NH:6][C:4](=[O:5])[CH2:3][C:2]([CH3:33])([CH3:1])[CH3:34])[C:8]([CH3:32])=[C:9]([CH3:31])[C:10]=3[O:14][CH2:13]2)=[CH:16][CH:17]=1)[CH3:28]
Reactant: CCOC(=O)CC(C)c1ccc(C2COc3c(C)c(C)c(NC(=O)CC(C)(C)C)c(C)c32)cc1
Solvent: CCOC(C)=O
Solvent: CCCCCC
Product: Cc1c(C)c2c(c(C)c1NC(=O)CC(C)(C)C)C(c1ccc(C(C)CCO)cc1)CO2
Yield: 85 %

Procedure:
Using ethyl 3-(4-(5-((3,3-dimethylbutanoyl)amino)-4,6,7-trimethyl-2,3-dihydro-1-benzofuran-3-yl)phenyl)butanoate obtained in Example 182, the title compound was synthesized in the same manner as in Example 193. Yield: 85%. Melting point: 145-147° C. (ethyl acetate-hexane).
Reaction SMILES: CC(C)([O-])C.[K+].[C:7]([OH:11])(=[O:10])[CH:8]=[CH2:9].[C:12](=[O:21])([O:18][CH2:19]Cl)[O:13][CH2:14][CH2:15][CH2:16][CH3:17].C1OCCOCCOCCOCCOCCOC1>CN(C=O)C>[C:12](=[O:21])([O:18][CH2:19][O:10][C:7](=[O:11])[CH:8]=[CH2:9])[O:13][CH2:14][CH2:15][CH2:16][CH3:17]
Reactant: C=CC(=O)O
Reactant: CCCCOC(=O)OCCl
Agent: C1COCCOCCOCCOCCOCCO1
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: C=CC(=O)OCOC(=O)OCCCC
Temperature: 25 °C
Reaction time: 48 h
Yield: 50.2 %

Procedure:
Potassium tert. butoxide (5.84 g, 0.052 mol ) was added to a solution of acrylic acid (4.47 g, 0.045 mol) in DMF (220 ml). Butyl chloromethyl carbonate (Example li, 6.5 g, 0.052 mol) in DMF (150 ml) was added to the resulting suspension. 18crown-6 (0.6 g) was then added and the reaction mixture was left with stirring at room temperature for 2 days. The reaction mixture was filtered and the solvent was removed under reduced pressure. The residue was dissolved in chloroform (100 ml) and washed with saturated aqueous sodium hydrogen carbonate (50 ml) and water (50 ml). The organic phase was dried (MgSO4) and the solvent removed under reduced pressure. Flash chromatography gave 4.57 g of the title product.
Reaction SMILES: [C:1]([O:5][C:6](=[O:17])[CH2:7]/[N:8]=[CH:9]/[CH2:10][C:11]([CH:14]1[CH2:16][CH2:15]1)([CH3:13])[CH3:12])(C)(C)C.[Cl:18][C:19]1[C:20]([F:37])=[C:21](/[CH:25]=[C:26](/[C:29]2[CH:34]=[CH:33][C:32]([Cl:35])=[CH:31][C:30]=2[F:36])\[C:27]#[N:28])[CH:22]=[CH:23][CH:24]=1.C(N(CC)CC)C>ClCCl>[CH3:1][O:5][C:6]([CH:7]1[CH:25]([C:21]2[CH:22]=[CH:23][CH:24]=[C:19]([Cl:18])[C:20]=2[F:37])[C:26]([C:29]2[CH:34]=[CH:33][C:32]([Cl:35])=[CH:31][C:30]=2[F:36])([C:27]#[N:28])[CH:9]([CH2:10][C:11]([CH:14]2[CH2:16][CH2:15]2)([CH3:13])[CH3:12])[NH:8]1)=[O:17]
Reactant: N#C/C(=C\c1cccc(Cl)c1F)c1ccc(Cl)cc1F
Reactant: CC(C)(C)OC(=O)C/N=C/CC(C)(C)C1CC1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COC(=O)C1NC(CC(C)(C)C2CC2)C(C#N)(c2ccc(Cl)cc2F)C1c1cccc(Cl)c1F
Temperature: 25 °C
Reaction time: 8 h
Yield: 49.8 %

Procedure:
To a solution of [3-cyclopropyl-3-methyl-but-(E)-ylideneamino]-acetic acid tert-butyl ester prepared in Example 99a (0.9 g, 3.76 mmol) and (Z)-3-(3-chloro-2-fluoro-phenyl)-2-(4-chloro-2-fluoro-phenyl)-acrylonitrile (1.16 g, 3.76 mmol) prepared in Example 52a in dichloromethane (100 mL) were added triethylamine (0.76 g, 7.5 mmol) and AgF (0.47 g, 3.76 mmol), in one portion. The mixture was stirred at room temperature for overnight. The mixture was then quenched with sat. NH4Cl and extracted with CH2Cl2. The organic phase was separated, filtered through celite and dried over Na2SO4, and concentrated. The residue was dissolved into methanol (40 mL), and DBU (3 mL) was added. The mixture was heated at 100° C. for 5 h, then cooled to room temperature, and concentrated. The residue was partitioned between ethyl acetate and water. The organic layer were separated, dried over MgSO4, and concentrated. The residue was purified by chromatography (EtOAc:hexanes=1:5, 1:3) to give rac-(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2-cyclopropyl-2-methyl-propyl)-pyrrolidine-2-carboxylic acid methyl ester as a white foam (0.95 g, 50%).
Reaction SMILES: [H-].[Na+].[C:3]([O:12]C)(=O)[CH2:4][CH2:5][CH2:6][C:7]([CH3:10])([CH3:9])[CH3:8].[C:14]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)(=[O:16])[CH3:15]>C1(C)C(C)=CC=CC=1>[C:17]1([C:14](=[O:16])[CH2:15][C:3]([CH2:4][CH2:5][CH2:6][C:7]([CH3:8])([CH3:9])[CH3:10])=[O:12])[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1
Reactant: CC(=O)c1ccccc1
Reactant: COC(=O)CCCC(C)(C)C
Agent: [H-]
Agent: [Na+]
Solvent: Cc1ccccc1C
Product: CC(C)(C)CCCC(=O)CC(=O)c1ccccc1
Temperature: 135 °C
Yield: 51.9 %

Procedure:
A 500 mL 4 neck round bottom flask equipped with mechanical stirring, a nitrogen inlet, a thermometer, a condenser, and an addition funnel was charged with 60% sodium hydride in mineral oil (20.5 g, 0.51 mol), methyl neo-octanoate (92.3 g, 0.58 mol), and xylene (42.8 g). The mixture was heated to reflux (135° C.), and then a solution of acetophenone (32.4 g, 0.27 mol) in xylene (19.1 g) was added over 1.25 h. The mixture was kept at reflux for an additional 1 h. After cooling to room temperature, the reaction was quenched by the careful addition of methanol (20 mL), and then acidified with 150 g/L sulfuric acid (180 mL). After separation of layers, the organic phase was washed with water (2×100 mL) and brine (100 mL). After drying by passing through anhydrous sodium sulfate, the solution was concentrated in vacuo at 70° C. down to 12 mbar to yield an orange liquid containing product in a crude yield of 63%. Vacuum distillation (200 mtorr) through a 15 cm Vigreux column yielded the product in the heart cut: 1-phenyl-3-neoheptyl-1,3-propanedione (37.2 g, 96% pure, 0.14 mol; 53% yield; bp: 94-135° C.). Dypnone was undetectable in the product.
Reaction SMILES: Cl.[Cl:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[C:13]([C:15]([O:17][CH3:18])=[O:16])([CH3:14])[CH2:12][NH:11][N:10]=2)=[CH:5][CH:4]=1.C(N(CC)CC)C.[F:26][C:27]([F:38])([F:37])[C:28]1[CH:33]=[CH:32][C:31]([N:34]=[C:35]=[O:36])=[CH:30][CH:29]=1>C(Cl)Cl>[F:26][C:27]([F:37])([F:38])[C:28]1[CH:29]=[CH:30][C:31]([NH:34][C:35]([N:11]2[CH2:12][C:13]([C:15]([O:17][CH3:18])=[O:16])([CH3:14])[C:9]([C:6]3[CH:5]=[CH:4][C:3]([Cl:2])=[CH:8][CH:7]=3)=[N:10]2)=[O:36])=[CH:32][CH:33]=1
Reactant: O=C=Nc1ccc(C(F)(F)F)cc1
Reactant: COC(=O)C1(C)CNN=C1c1ccc(Cl)cc1
Agent: Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: COC(=O)C1(C)CN(C(=O)Nc2ccc(C(F)(F)F)cc2)N=C1c1ccc(Cl)cc1
Yield: 95 %

Procedure:
3-(4-chlorophenyl)-4-carbomethoxy-4-methyl-4,5-dihydro-1H-pyrazole hydrochloride (Example P) (10 mmole), triethylamine (20 mmole), methylene chloride (30 ml) were added together and stirred for 10 minutes, whereon 10 mmole of 4-trifluoromethylphenyl isocyanate was added and after 30 minutes the resulting mixture was washed twice with water, dried with magnesium sulfate and concentrated giving a 95% yield of N-(4-trifluoromethylphenyl)-3-(4-chlorophenyl)-4-carbomethoxy-4-methyl-4,5-dihydro-1H-pyrazole-1-carboxamide. NMR data was consistent with the structure.
Reaction SMILES: [Cl:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][NH2:7])=[CH:4][CH:3]=1.Br[C:11]1[CH:20]=[N:19][CH:18]=[CH:17][C:12]=1[C:13]([O:15][CH3:16])=[O:14]>>[Cl:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][NH:7][N:19]2[CH:18]=[CH:17][C:12]([C:13]([O:15][CH3:16])=[O:14])=[CH:11][CH2:20]2)=[CH:4][CH:3]=1
Reactant: NCc1ccc(Cl)cc1
Reactant: COC(=O)c1ccncc1Br
Product: COC(=O)C1=CCN(NCc2ccc(Cl)cc2)C=C1
Yield: 72 %

Procedure:
The title compound was prepared in 72% yield from 4-chlorobenzylamine and methyl 3-bromoisonicotinate according to the procedure for Preparation 4A. 1H NMR (400 MHz, CDCl3): δ 8.14 (s, 1H), 7.94 (d, 1H, J=5.0 Hz), 7.82 (br s, 1H), 7.62 (d, 1H, J=5.0 Hz), 7.24-7.32 (m, 4H), 4.47 (d, 2H, J=5.7 Hz), 3.89 (s, 3H). [M+H] calc'd for C14H13ClN2O2, 277, 279; found 277, 279.
Reaction SMILES: [Cl:1][C:2]1[C:7]([Cl:8])=[CH:6][CH:5]=[CH:4][C:3]=1[N:9]1[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][CH2:17][CH2:18][O:19][C:20]2[CH:29]=[C:28]3[C:23]([CH2:24][CH2:25][C:26](=[O:32])[N:27]3[CH2:30][OH:31])=[CH:22][CH:21]=2)[CH2:11][CH2:10]1.C(N(CC)CC)C.CS(Cl)(=O)=O.[C:45]([NH:48][CH2:49][CH2:50][CH2:51][C:52](O)=[O:53])(=[O:47])[CH3:46]>ClCCl>[C:45]([NH:48][CH2:49][CH2:50][CH2:51][C:52]([O:31][CH2:30][N:27]1[C:28]2[C:23](=[CH:22][CH:21]=[C:20]([O:19][CH2:18][CH2:17][CH2:16][CH2:15][N:12]3[CH2:13][CH2:14][N:9]([C:3]4[CH:4]=[CH:5][CH:6]=[C:7]([Cl:8])[C:2]=4[Cl:1])[CH2:10][CH2:11]3)[CH:29]=2)[CH2:24][CH2:25][C:26]1=[O:32])=[O:53])(=[O:47])[CH3:46]
Reactant: CC(=O)NCCCC(=O)O
Reactant: O=C1CCc2ccc(OCCCCN3CCN(c4cccc(Cl)c4Cl)CC3)cc2N1CO
Agent: CS(=O)(=O)Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(=O)NCCCC(=O)OCN1C(=O)CCc2ccc(OCCCCN3CCN(c4cccc(Cl)c4Cl)CC3)cc21
Reaction time: 0.42 h

Procedure:
To a suspension of hemiaminal A1 (2.6 g, 5.5 mmol) in dichloromethane (30 mL) was added triethylamine (2.3 mL, 16.4 mmol), followed by addition of methanesulfonyl chloride (0.47 g, 6.0 mmol) over 3 min. The reaction mixture was stirred for 25 min and then N-acetyl-4-aminobutyric acid (1.6 g, 10.1 mmol) added. The reaction mixture was then heated at reflux for 18 h, cooled and washed with sat. NaHCO3 (aq). The organic phase was dried over MgSO4, filtered and evaporated. The residue was further purified on silica eluting with 1:1:0.1 to 1:1:0.2 dichloromethane/ethyl acetate/methanol to give the title compound as an off white solid (1.1 g, 34%).
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([NH:8][CH2:9][C:10]([NH:12][C:13]2[CH:18]=[CH:17][C:16]([CH2:19][N:20]([CH3:22])[CH3:21])=[CH:15][CH:14]=2)=[O:11])=[CH:4][CH:3]=1.[Cl:23][C:24]1[CH:29]=[CH:28][C:27](OB(O)O)=[CH:26][CH:25]=1>>[Cl:23][C:24]1[CH:29]=[CH:28][C:27]([C:2]2[CH:7]=[CH:6][C:5]([NH:8][CH2:9][C:10]([NH:12][C:13]3[CH:18]=[CH:17][C:16]([CH2:19][N:20]([CH3:22])[CH3:21])=[CH:15][CH:14]=3)=[O:11])=[CH:4][CH:3]=2)=[CH:26][CH:25]=1
Reactant: CN(C)Cc1ccc(NC(=O)CNc2ccc(Br)cc2)cc1
Reactant: OB(O)Oc1ccc(Cl)cc1
Product: CN(C)Cc1ccc(NC(=O)CNc2ccc(-c3ccc(Cl)cc3)cc2)cc1

Procedure:
Prepared analogously to Example 130a starting from 2-(4-bromo-phenylamino)-N-(4-dimethylaminomethyl-phenyl)-acetamide (Example 163a) and 4-chloro-phenyl-boric acid.
Reaction SMILES: S(Cl)([Cl:3])=O.[Cl:5][S:6]([C:9]1[C:10]([O:18][CH3:19])=[C:11]([CH:15]=[CH:16][CH:17]=1)[C:12](O)=[O:13])(=[O:8])=[O:7]>CN(C)C=O>[Cl:5][S:6]([C:9]1[C:10]([O:18][CH3:19])=[C:11]([CH:15]=[CH:16][CH:17]=1)[C:12]([Cl:3])=[O:13])(=[O:8])=[O:7]
Reactant: COc1c(C(=O)O)cccc1S(=O)(=O)Cl
Reactant: O=S(Cl)Cl
Solvent: CN(C)C=O
Product: COc1c(C(=O)Cl)cccc1S(=O)(=O)Cl
Temperature: 60 °C
Reaction time: 2 h

Procedure:
Three drops of N,N-dimethylformamide were added to a thionyl chloride (4.37 mL) suspension of 3-(chlorosulfonyl)-2-methoxybenzoic acid (3.00 g), followed by stirring at 60° C. for 2 hours. The solvent was evaporated, and this was azeotroped with toluene to obtain 3-(chlorosulfonyl)-2-methoxybenzoyl chloride (3.22 g).
Reaction SMILES: Br[C:2]1[C:3]2[N:4]([N:8]=[C:9]([Cl:11])[N:10]=2)[CH:5]=[CH:6][CH:7]=1.[Cl:12][C:13]1[CH:14]=[CH:15][C:16]([O:22][CH2:23][CH2:24][CH3:25])=[C:17](B(O)O)[CH:18]=1>>[Cl:11][C:9]1[N:10]=[C:3]2[C:2]([C:15]3[CH:14]=[C:13]([Cl:12])[CH:18]=[CH:17][C:16]=3[O:22][CH2:23][CH2:24][CH3:25])=[CH:7][CH:6]=[CH:5][N:4]2[N:8]=1
Reactant: CCCOc1ccc(Cl)cc1B(O)O
Reactant: Clc1nc2c(Br)cccn2n1
Product: CCCOc1ccc(Cl)cc1-c1cccn2nc(Cl)nc12

Procedure:
2-Chloro-8-(5-chloro-2-propoxy-phenyl)-[1,2,4]triazolo[1,5-a]pyridine was prepared from 8-bromo-2-chloro-[1,2,4]triazolo[1,5-a]pyridine and 5-chloro-2-propoxyphenylboronic acid in a manner analogous to Example 2c (0.46 g, 66%). MS=323 (MH)+.
Reaction SMILES: I[C:2]1[CH:9]=[CH:8][CH:7]=[CH:6][C:3]=1[CH2:4][OH:5].[CH:10]1[CH2:15][CH2:14][CH2:13][CH2:12][CH:11]=1.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.CCN(CC)CC>CO.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH:10]1([C:2]2[CH:9]=[CH:8][CH:7]=[CH:6][C:3]=2[CH2:4][OH:5])[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]1
Reactant: OCc1ccccc1I
Reactant: C1=CCCCC1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: Cc1ccccc1P(c1ccccc1C)c1ccccc1C
Solvent: CO
Solvent: CCN(CC)CC
Product: OCc1ccccc1C1CCCCC1
Yield: 42 %

Procedure:
According to example 61, 10.0 g of 2-iodobenzyl alcohol was treated with 25 mL of cyclohexene (Aldrich) using 0.96 g of Pd(OAc)2, 2.60 g of tri-ortho-tolylphosphine, and 6.6 mL of Et3N at 110° C. for 48 h. The resulting olefin mixture was hydrogenated for 6.5 h using 0.36 g of 5% Pt(C) in MeOH to afford 3.37 g (42%) of 2-cyclohexyl benzyl alcohol as a light yellow liquid.
Reaction SMILES: [CH3:1][Si:2]([CH3:9])([CH3:8])[NH:3][Si](C)(C)C.N1[CH:14]=[N:13][CH:12]=[N:11]1.N>S1(C2C(=CC=CC=2)C(=O)N1)(=O)=O>[CH3:1][Si:2]([CH3:9])([CH3:8])[N:3]1[CH:14]=[N:13][CH:12]=[N:11]1
Reactant: c1nc[nH]n1
Reactant: C[Si](C)(C)N[Si](C)(C)C
Agent: N
Agent: O=C1NS(=O)(=O)c2ccccc21
Product: C[Si](C)(C)n1cncn1
Temperature: 126 °C
Yield: 124.7 %

Procedure:
23.4 ml (0.11 mole) of hexamethyldisilazane were added to a mixture consisting of 10.35 g (0.15 mole) of 1,2,4-triazole and 127 mg (0.75 mmole) of saccharin heated to 126° C. and evolution of ammonia started immediately. After refluxing for 30 minutes, the calculated amount of ammonia was evolved as determined by the method described in Example 1A. Vacuum distillation yielded 19.37 g (91.6%) of 1-trimethylsilyl-1,2,4-triazole boiling at 76.5°-78.0° C. at 12 mm Hg and nD 25=1.4592.