Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH:1]1[C:12](=[O:13])[C:11]2[N:9]([CH3:10])[CH:8]=[N:7][C:6]=2[N:4]([CH3:5])[C:2]1=[O:3].[H-].[Na+].CS([CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH:27]=[CH2:28])(=O)=O.O>CS(C)=O.C(OCC)(=O)C>[CH2:28]([N:1]1[C:12](=[O:13])[C:11]2[N:9]([CH3:10])[CH:8]=[N:7][C:6]=2[N:4]([CH3:5])[C:2]1=[O:3])[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23][CH2:22][CH:21]=[CH2:20]
Reactant: C=CCCCCCCCS(C)(=O)=O
Reactant: Cn1cnc2c1c(=O)[nH]c(=O)n2C
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CS(C)=O
Solvent: CCOC(C)=O
Product: C=CCCCCCCCn1c(=O)c2c(ncn2C)n(C)c1=O
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 24.2 %

Procedure:
Theobromine (1.98 g, 11 mmol) was added to a suspension of NaH (600 mg of a 50% mineral oil slurry, 12 mmol) in DMSO (15 ml). After 15 min, 9-methanesulfonyl-1-nonene (2.25 g, 11 mmol) was added and the reaction mixture was stirred for 6 days at 25° C. The reaction mixture was poured into 60 ml of water and extracted with dichloromethane (3×50 ml). The organic portions were combined, dried with magnesium sulfate, and evaporated to give a dark oil. Chromatography (silica, ethyl acetate) gave 1-(8-nonenyl)-3,7-dimethylxanthine (CT1550) as a colorless oil (810 mg, 26% yield).
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([S:8](Cl)(=[O:10])=[O:9])=[CH:4][C:3]=1[C:12]([F:15])([F:14])[F:13].[NH2:16][C:17]1[C:18]([C:24]#[N:25])=[N:19][CH:20]=[C:21]([CH3:23])[CH:22]=1>N1C=CC=CC=1>[C:24]([C:18]1[C:17]([NH:16][S:8]([C:5]2[CH:6]=[CH:7][C:2]([CH3:1])=[C:3]([C:12]([F:15])([F:14])[F:13])[CH:4]=2)(=[O:10])=[O:9])=[CH:22][C:21]([CH3:23])=[CH:20][N:19]=1)#[N:25]
Reactant: Cc1cnc(C#N)c(N)c1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1C(F)(F)F
Solvent: c1ccncc1
Product: Cc1cnc(C#N)c(NS(=O)(=O)c2ccc(C)c(C(F)(F)F)c2)c1

Procedure:
Prepared from 2.92 g (11.3 mmol) of 4-methyl-3-trifluoromethyl-benzenesulfonyl chloride and 1.25 g (9.41 mmol) of 3-amino-5-methyl-pyridine-2-carbonitrile in 4 mL pyridine using procedure x. Yield: 1.13 g of a white solid. LC-MSD, m/z for C15H12F3N3O2S [M+H]+=356.0
Reaction SMILES: [C:1]([C:3](=[CH:13]OCC)[C:4]([NH:6][CH:7]1[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]1)=[O:5])#[N:2].Cl.[NH:18]([C:20]1[CH:29]=[CH:28][C:23]([C:24]([O:26][CH3:27])=[O:25])=[CH:22][CH:21]=1)[NH2:19].CCN(C(C)C)C(C)C>C(O)C>[NH2:2][C:1]1[N:18]([C:20]2[CH:21]=[CH:22][C:23]([C:24]([O:26][CH3:27])=[O:25])=[CH:28][CH:29]=2)[N:19]=[CH:13][C:3]=1[C:4](=[O:5])[NH:6][CH:7]1[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]1
Reactant: CCOC=C(C#N)C(=O)NC1CCCCC1
Reactant: COC(=O)c1ccc(NN)cc1
Agent: Cl
Solvent: CCO
Solvent: CCN(C(C)C)C(C)C
Product: COC(=O)c1ccc(-n2ncc(C(=O)NC3CCCCC3)c2N)cc1
Temperature: 70 °C

Procedure:
2-cyano-N-cyclohexyl-3-ethoxy-prop-2-enamide (Intermediate #17) (605 mg, 2.73 mmol) and methyl 4-hydrazinylbenzoate hydrochloride (Intermediate #123) (552 mg, 2.73 mmol) were suspended in ethanol (20 mL). DIPEA (351 mg, 2.73 mmol) was added and the mixture heated to 70° C. for 1 h. The reaction mixture was cooled to ambient and the resulting precipitate recovered by filtration, washed with ether and dried in vacuo to give the title compound as a white solid. (618 mg 66%)
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][C:6]([CH:10]=[O:11])=[CH:7][CH:8]=2)[CH:3]=[N:2]1.[Br:12][C:13]1[CH:18]=[C:17]([Cl:19])[CH:16]=[CH:15][C:14]=1[CH2:20]Br>>[Br:12][C:13]1[CH:18]=[C:17]([Cl:19])[CH:16]=[CH:15][C:14]=1[CH2:20][N:1]1[C:9]2[C:4](=[CH:5][C:6]([CH:10]=[O:11])=[CH:7][CH:8]=2)[CH:3]=[N:2]1
Reactant: Clc1ccc(CBr)c(Br)c1
Reactant: O=Cc1ccc2[nH]ncc2c1
Product: O=Cc1ccc2c(cnn2Cc2ccc(Cl)cc2Br)c1

Procedure:
1-(2-Bromo-4-chloro-benzyl)-1H-indazole-5-carbaldehyde was prepared from 1H-indazole-5-carbaldehyde and 2-bromo-1-bromomethyl-4-chloro-benzene following General Procedure A.
Reaction SMILES: [C:1]1([CH2:7][C:8](Cl)=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH2:11]([NH:18][C:19]([C:21]1[S:25][C:24]([NH2:26])=[N:23][C:22]=1[CH3:27])=[O:20])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1>>[CH2:11]([NH:18][C:19]([C:21]1[S:25][C:24]([NH:26][C:8](=[O:9])[CH2:7][C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)=[N:23][C:22]=1[CH3:27])=[O:20])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1
Reactant: O=C(Cl)Cc1ccccc1
Reactant: Cc1nc(N)sc1C(=O)NCc1ccccc1
Product: Cc1nc(NC(=O)Cc2ccccc2)sc1C(=O)NCc1ccccc1
Yield: 17 %

Procedure:
Following the procedure as described in Example 2, making variations only as required to use phenylacetyl chloride in place of benzoyl chloride to react with 2-amino-4-methylthiazole-5-carboxylic acid benzylamide, the title compound was obtained as a white solid in 17% yield; m.p. 63-65° C.; 1H NMR (CDCl3, 300 MHz) δ 7.39-7.23 (m, 10H), 5.95 (s, 1H), 4.56 (d, J=5.4 Hz, 2H), 3.79 (s, 2H), 2.54 (s, 3H); MS (ES+) m/z 366.1 (M+1).
Reaction SMILES: [C:1]([C:4]1[CH:28]=[CH:27][C:7]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][C:13]([CH:16](O)[C:17]3[CH:18]=[C:19]([CH:23]=[CH:24][CH:25]=3)[C:20]([OH:22])=[O:21])=[CH:12][CH:11]=2)=[C:6]([CH3:29])[C:5]=1[OH:30])(=[O:3])[CH3:2].C([SiH](CC)CC)C.B(F)(F)F.CCOCC.ClCCl>O>[C:1]([C:4]1[CH:28]=[CH:27][C:7]([O:8][CH2:9][C:10]2[CH:11]=[CH:12][C:13]([CH2:16][C:17]3[CH:18]=[C:19]([CH:23]=[CH:24][CH:25]=3)[C:20]([OH:22])=[O:21])=[CH:14][CH:15]=2)=[C:6]([CH3:29])[C:5]=1[OH:30])(=[O:3])[CH3:2]
Reactant: CC(=O)c1ccc(OCc2ccc(C(O)c3cccc(C(=O)O)c3)cc2)c(C)c1O
Agent: CC[SiH](CC)CC
Agent: FB(F)F
Solvent: O
Solvent: ClCCl
Solvent: CCOCC
Product: CC(=O)c1ccc(OCc2ccc(Cc3cccc(C(=O)O)c3)cc2)c(C)c1O
Yield: 70.2 %

Procedure:
A solution of 3-{[4-(4-acetyl-3-hydroxy-2-methyl-phenoxymethyl)-phenyl]-hydroxy-methyl}-benzoic acid (80 mg, 0.197 mmol), triethylsilane (250 μL, 1.57 mmol), boron trifluoride diethyl etherate (70 μL, 0.542 mmol), and dichloromethane (2 mL) is stirred 1 hr at room temperature. The mixture is diluted with water and extracted with ethyl acetate (2×10 mL). The combined extracts are dried over magnesium sulfate, filtered and concentrated. The residue is recrystallized from dichloromethane/hexanes to give (54 mg, 70%) the title compound, as a white solid. 1H NMR (DMSO-d6) δ 12.92 (bs, 1H), 12.85 (s, 1H), 7.78-7.82 (m, 3H), 7.27-7.49 (m, 6H), 6.72 (d, 1H), 5.23 (s, 2H), 4.06 (s, 2H), 2.52 (s, 3H), 2.04 (s, 3H). LCMS M−1 389.
Reaction SMILES: [OH-].[Na+].[Cl:3][C:4]1[CH:11]=[CH:10][C:9]([N+:12]([O-:14])=[O:13])=[CH:8][C:5]=1[CH:6]=O.[CH:15](=[O:18])[CH2:16][CH3:17].C(O)(=O)C>O.CO>[Cl:3][C:4]1[CH:11]=[CH:10][C:9]([N+:12]([O-:14])=[O:13])=[CH:8][C:5]=1[CH:6]=[C:16]([CH3:17])[CH:15]=[O:18]
Reactant: O=Cc1cc([N+](=O)[O-])ccc1Cl
Reactant: CCC=O
Agent: [Na+]
Agent: [OH-]
Solvent: CC(=O)O
Solvent: CO
Solvent: O
Product: CC(C=O)=Cc1cc([N+](=O)[O-])ccc1Cl
Temperature: 25 °C
Reaction time: 48 h
Yield: 78 %

Procedure:
4 g of NaOH dissolved in 20 ml of water were added to a suspension of 185.5 g (1 mole) of 2-chloro-5-nitrobenzaldehyde in 500 ml of methanol, after which 70 g (1.2 moles) of propionaldehyde were added dropwise while cooling to 10°-15° C. The mixture was stirred for 2 days at room temperature and then neutralized with glacial acetic acid, and the precipitated solid was isolated by filtration under suction, washed with water and dried at 50° C. under reduced pressure to give the product of melting point 99°-102° C. in 78% yield.
Reaction SMILES: [CH3:1][N:2]1[C@@H:19]2[CH2:20][C:7]3[CH:8]=[CH:9][C:10]([O:22][CH3:23])=[C:11]4[O:12][C@H:13]5[C:14]([CH2:16][CH2:17][C@:18]2([OH:21])[C@:5]5([C:6]=34)[CH2:4][CH2:3]1)=[O:15].[Cl:24]CCl>[Pd].C(O)(C)C>[CH3:1][N:2]1[C@@H:19]2[CH2:20][C:7]3[CH:8]=[CH:9][C:10]([O:22][CH3:23])=[C:11]4[O:12][C@H:13]5[C:14]([CH2:16][CH2:17][C@:18]2([OH:21])[C@:5]5([C:6]=34)[CH2:4][CH2:3]1)=[O:15].[ClH:24]
Reactant: ClCCl
Agent: [Pd]
Agent: COc1ccc2c3c1O[C@H]1C(=O)CC[C@@]4(O)[C@@H](C2)N(C)CC[C@]314
Solvent: CC(C)O
Product: Cl

Procedure:
To a 250 mL hydrogenation bottle was charged 1.5 g (4.75 mmol, prepared via Rh catalyst rearrangement, 424 ppm 14-hydroxycodeinone) of oxycodone base, 6 mL of dichloromethane (DCM) and 2 mL of isopropanol (IPA). The mixture was agitated until a solution was obtained, then 0.15 g of 10% Pd/C was added. The mixture was hydrogenated with agitation at 35° C., 25 psi H2 and processed to isolated oxycodone HCl in portions after one and two days of hydrogenation.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([N:9]([CH2:21][CH2:22][C:23]2[CH:24]=[N:25][C:26]([C:29]([F:32])([F:31])[F:30])=[CH:27][CH:28]=2)[C:10](=[O:20])[C:11]([C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=2)=[O:12])[CH:5]=[CH:6][C:7]=1[CH3:8].[BH4-].[Na+]>CO>[CH3:1][C:2]1[CH:3]=[C:4]([N:9]([CH2:21][CH2:22][C:23]2[CH:24]=[N:25][C:26]([C:29]([F:31])([F:32])[F:30])=[CH:27][CH:28]=2)[C:10](=[O:20])[C@H:11]([C:13]2[CH:14]=[CH:15][C:16]([F:19])=[CH:17][CH:18]=2)[OH:12])[CH:5]=[CH:6][C:7]=1[CH3:8]
Reactant: Cc1ccc(N(CCc2ccc(C(F)(F)F)nc2)C(=O)C(=O)c2ccc(F)cc2)cc1C
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Product: Cc1ccc(N(CCc2ccc(C(F)(F)F)nc2)C(=O)[C@@H](O)c2ccc(F)cc2)cc1C
Temperature: 0 °C
Reaction time: 12 h
Yield: 96.7 %

Procedure:
A solution of N-(3,4-dimethyl-phenyl)-2-(4-fluoro-phenyl)-2-oxo-N-[2-(6-trifluoromethyl-pyridin-3-yl)-ethyl]-acetamide (515 mg, 1.16 mmol) was dissolved in MeOH (8 mL), cooled to 0° C. and treated with NaBH4 (88 mg, 2.33 mmol) and stirred for 12 h at ambient temperature. The reaction mixture was quenched with aqueous K2CO3 (2 M, 1 mL), concentrated, then redissolved in EtOAc (15 mL) and washed with aqueous K2CO3 (2 M, 3×15 mL). The combined aqueous layers were extracted with EtOAc (3×15 mL) and the combined organic layers dried over sodium sulfate. Concentration and purification by chromatography (SiO2, heptane:ethyl acetate=95:5 to 60:40) afforded the racemic compound (501 mg, 97%) as a lightyellow oil. Separation by chromatography on a chiral column provided the title compound as a colourless oil MS m/e: 447.2 [M+H]+ which crystallized upon standing.
Reaction SMILES: [F:1][C:2]([F:22])([F:21])[C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([O:9][C:10]2[CH:15]=[CH:14][C:13]([CH2:16][C:17]([O:19]C)=[O:18])=[CH:12][CH:11]=2)[CH:4]=1.[OH-].[K+]>O>[F:1][C:2]([F:21])([F:22])[C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([O:9][C:10]2[CH:15]=[CH:14][C:13]([CH2:16][C:17]([OH:19])=[O:18])=[CH:12][CH:11]=2)[CH:4]=1
Reactant: COC(=O)Cc1ccc(Oc2cccc(C(F)(F)F)c2)cc1
Agent: [K+]
Agent: [OH-]
Solvent: O
Product: O=C(O)Cc1ccc(Oc2cccc(C(F)(F)F)c2)cc1

Procedure:
A mixture of 12.40 g of methyl [p-(α,α,α-trifluoro-m-tolyloxy)phenyl]acetate, 30 ml of 20% KOH and 10 ml of water is refluxed overnight. After dilution with 250 ml of water, the clear orange solution is acidified and extracted with two 50 ml portions of chloroform. The combined organic extracts are washed with two 50 ml portions of water, saturated brine, and dried over MgSO4. Evaporation of the solvent affords white crystals, mp 61°-63° C. (from petroleum ether). Recrystallization from petroleum ether affords colorless blades, mp 61°-62.5° C.
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].Br[CH:8]([C@H:25]1[CH2:30][CH2:29][C@H:28]([N:31]2[C:39](=[O:40])[C:38]3[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=3)[C:32]2=[O:41])[CH2:27][CH2:26]1)[C:9]([NH:11][C:12]1[CH:13]=[N:14][C:15]2[C:20]([C:21]=1[OH:22])=[N:19][C:18]([O:23][CH3:24])=[CH:17][CH:16]=2)=[O:10].ClCCl.CO>CN(C)C=O>[CH3:24][O:23][C:18]1[N:19]=[C:20]2[C:15](=[CH:16][CH:17]=1)[N:14]=[CH:13][C:12]1[NH:11][C:9](=[O:10])[CH:8]([C@H:25]3[CH2:30][CH2:29][C@H:28]([N:31]4[C:32](=[O:41])[C:33]5[C:38](=[CH:37][CH:36]=[CH:35][CH:34]=5)[C:39]4=[O:40])[CH2:27][CH2:26]3)[O:22][C:21]2=1
Reactant: COc1ccc2ncc(NC(=O)C(Br)[C@H]3CC[C@H](N4C(=O)c5ccccc5C4=O)CC3)c(O)c2n1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CO
Solvent: ClCCl
Product: COc1ccc2ncc3c(c2n1)OC([C@H]1CC[C@H](N2C(=O)c4ccccc4C2=O)CC1)C(=O)N3
Temperature: 25 °C
Reaction time: 2 h

Procedure:
Potassium carbonate (2.49 g, 18.03 mmol, 3.0 eq) is added at room temperature to a stirred solution of 2-bromo-[trans-4-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-cyclohexyl]-N-(4-hydroxy-6-methoxy-[1,5]naphthyridin-3-yl)-acetamide (3.24 g, 6.01 mmol, 1.0 eq) in N,N-dimethylformamide (30 mL). After 16 hours stirring at room temperature and 2 hours stirring at 55° C., solvent is removed and the residue is purified by column chromatography (silica gel, eluent: dichloromethane:methanol, 50:1, v/v) to afford 2-[trans-4-(6-methoxy-2-oxo-2,3-dihydro-1H-4-oxa-1,5,9-triaza-phenanthren-3-yl)-cyclohexyl]-isoindole-1,3-dione as a light yellow solid (1.35 g, 49% yield).
Reaction SMILES: [NH2:1][C:2]1[C:3]2[N:4]([C:8]([C@@H:26]3[CH2:30][CH2:29][CH2:28][NH:27]3)=[N:9][C:10]=2[C:11]2[CH:25]=[CH:24][C:14]([C:15]([NH:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=3)=[O:16])=[CH:13][CH:12]=2)[CH:5]=[CH:6][N:7]=1.[CH:31]1([C:34]#[C:35][C:36](O)=[O:37])[CH2:33][CH2:32]1>>[NH2:1][C:2]1[C:3]2[N:4]([C:8]([C@@H:26]3[CH2:30][CH2:29][CH2:28][N:27]3[C:36](=[O:37])[C:35]#[C:34][CH:31]3[CH2:33][CH2:32]3)=[N:9][C:10]=2[C:11]2[CH:25]=[CH:24][C:14]([C:15]([NH:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=3)=[O:16])=[CH:13][CH:12]=2)[CH:5]=[CH:6][N:7]=1
Reactant: O=C(O)C#CC1CC1
Reactant: Nc1nccn2c([C@@H]3CCCN3)nc(-c3ccc(C(=O)Nc4ccccn4)cc3)c12
Product: Nc1nccn2c([C@@H]3CCCN3C(=O)C#CC3CC3)nc(-c3ccc(C(=O)Nc4ccccn4)cc3)c12
Yield: 26 %

Procedure:
This compound was prepared, in an analogous manner as described in Example 2, from the compound described in intermediate 2b and 3-cyclopropylpropiolic acid, to afford the title compound (8 mg, 26%). Data: UPLC (C) Rt: 1.73 min; m/z 492.3 (M+H)+.
Reaction SMILES: [NH:1]1[CH:5]=[C:4]([C:6]2[N:11]=[CH:10][C:9]3[CH:12]=[N:13][N:14]([C:15]4[N:20]=[C:19]([N:21]5[CH2:27][CH2:26][CH2:25][N:24]([C:28]([O-:30])=[O:29])[CH2:23][CH2:22]5)[CH:18]=[CH:17][CH:16]=4)[C:8]=3[CH:7]=2)[CH:3]=[N:2]1.Br[CH2:32][CH:33]1[CH2:35][CH2:34]1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[CH:35]1([CH2:34][N:1]2[CH:5]=[C:4]([C:6]3[N:11]=[CH:10][C:9]4[CH:12]=[N:13][N:14]([C:15]5[N:20]=[C:19]([N:21]6[CH2:27][CH2:26][CH2:25][N:24]([C:28]([O:30][C:4]([CH3:6])([CH3:5])[CH3:3])=[O:29])[CH2:23][CH2:22]6)[CH:18]=[CH:17][CH:16]=5)[C:8]=4[CH:7]=3)[CH:3]=[N:2]2)[CH2:33][CH2:32]1
Reactant: BrCC1CC1
Reactant: O=C([O-])N1CCCN(c2cccc(-n3ncc4cnc(-c5cn[nH]c5)cc43)n2)CC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)N1CCCN(c2cccc(-n3ncc4cnc(-c5cnn(CC6CC6)c5)cc43)n2)CC1
Temperature: 25 °C
Reaction time: 18 h
Yield: 180.8 %

Procedure:
A suspension of 4-(6-(6-(1H-pyrazol-4-yl)-1H-pyrazolo[4,3-c]pyridin-1-yl)pyridin-2-yl)-1,4-diazepane-1-carboxylate (200 mg, 0.43 mmol), (bromomethyl)cyclopropane (100 mg, 0.65 mmol), and K2CO3 (120 mg, 0.87 mmol) in DMF (10 mL) was stirred at room temperature for 18 hours. The reaction mixture was extracted with EtOAc (100 mL), washed with brine (50 mL), dried over MgSO4, and concentrated under reduced pressure. The crude was purified by silica gel chromatography using petroleum ether/EtOAc (2/1) as eluting solvents to afford tert-butyl 4-(6-(6-(1-(cyclopropylmethyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-c]pyridin-1-yl)pyridin-2-yl)-1,4-diazepane-1-carboxylate as a white solid (200 mg, 89.6%). MS (ESI) m/z: 515 [M+H]+.
Reaction SMILES: Cl[C:2]1[N:7]([CH3:8])[C:6](=[O:9])[N:5]([CH3:10])[C:4](=[O:11])[C:3]=1[CH:12]=[O:13].[CH3:14][S-:15].[Na+]>>[CH3:8][N:7]1[C:2]([S:15][CH3:14])=[C:3]([CH:12]=[O:13])[C:4](=[O:11])[N:5]([CH3:10])[C:6]1=[O:9]
Reactant: C[S-]
Reactant: Cn1c(Cl)c(C=O)c(=O)n(C)c1=O
Agent: [Na+]
Product: CSc1c(C=O)c(=O)n(C)c(=O)n1C

Procedure:
The process described in Method D was followed. 6-Chloro-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carbaldehyde (0.404 g, 2.00 mmol) and sodium thiomethoxide (0.154 g, 2.20 mmol in 4 ml 1,4-dioxane) were used to obtain the title compound. The crude product was purified by washing with n-pentane.
Reaction SMILES: [Cl:1][C:2]([Cl:34])([Cl:33])[CH2:3][O:4][C:5]([C@@H:7]1[CH2:12][CH2:11][CH2:10][N:9]([C:13](=[O:32])[C@@H:14]([NH:16][C:17](=[O:31])[C@@H:18]([NH:22][C:23](=[O:30])[C:24]([C:28]#[N:29])([CH3:27])[CH:25]=[CH2:26])[CH:19]([CH3:21])[CH3:20])[CH3:15])[NH:8]1)=[O:6].Br[C:36]1[CH:45]=[C:44]2[C:39]([CH:40]=[CH:41][C:42]([C@H:46]([OH:48])[CH3:47])=[N:43]2)=[CH:38][CH:37]=1.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C1(CNCC2CCCCC2)CCCCC1>C(#N)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:34][C:2]([Cl:33])([Cl:1])[CH2:3][O:4][C:5]([C@@H:7]1[CH2:12][CH2:11][CH2:10][N:9]([C:13](=[O:32])[C@@H:14]([NH:16][C:17](=[O:31])[C@@H:18]([NH:22][C:23](=[O:30])[C:24]([C:28]#[N:29])([CH3:27])/[CH:25]=[CH:26]/[C:36]2[CH:45]=[C:44]3[C:39]([CH:40]=[CH:41][C:42]([C@H:46]([OH:48])[CH3:47])=[N:43]3)=[CH:38][CH:37]=2)[CH:19]([CH3:21])[CH3:20])[CH3:15])[NH:8]1)=[O:6]
Reactant: C[C@@H](O)c1ccc2ccc(Br)cc2n1
Reactant: C=CC(C)(C#N)C(=O)N[C@H](C(=O)N[C@@H](C)C(=O)N1CCC[C@@H](C(=O)OCC(Cl)(Cl)Cl)N1)C(C)C
Agent: [Pd+2]
Agent: C1CCC(CNCC2CCCCC2)CC1
Agent: CC(=O)[O-]
Solvent: CC#N
Product: CC(C)[C@H](NC(=O)C(C)(C#N)/C=C/c1ccc2ccc([C@@H](C)O)nc2c1)C(=O)N[C@@H](C)C(=O)N1CCC[C@@H](C(=O)OCC(Cl)(Cl)Cl)N1
Temperature: 120 °C
Yield: 18.2 %

Procedure:
(S)-1-{(S)-2-[(S)-2-(2-Cyano-2-methyl-but-3-enoylamino)-3-methyl-butyrylamino]-propionyl}-hexahydro-pyridazine-3-carboxylic acid 2,2,2-trichloro-ethyl ester (283 mg, 0.527 mmol), (R)-1-(7-bromo-quinolin-2-yl)-ethanol (146 mg, 0.580 mmol), palladium(II) acetate (24 mg, 0.105 mmol) and tri(o-tolyl)phosphine (32 mg, 0.105 mmol) were suspended in anhydrous acetonitrile and N,N-dicyclohexylmethylamine (113 mg, 124 μL, 0.580 mmol) added. The vessel was sealed and heated in a microwave reactor at 120° C. for 40 minutes. The mixture was evaporated and the residue dissolved in ethyl acetate and washed with saturated ammonium chloride solution (2×), water then saturated brine. The organic layer was dried over anhydrous sodium sulfate, filtered and evaporated. The residue was purified by silica gel chromatography using a gradient of iso-hexanes/ethyl acetate 1:1 to 0:1 to give the title compound (68 mg, 39%) as a yellow solid as a mixture of diastereoisomers. 1H NMR (300 MHz, CD3OD) δ 0.92-0.98 (m, 3H) 1.01 (d, J=6.9 Hz, 3H), 1.27 (app t, J=7.1 Hz, 3H), 1.59 (d, J=5.5 Hz, 3H), 1.68-1.81 (m, 2H), 1.86 (s, 3H), 1.88-1.99 (m, 1H), 2.10-2.25 (m, 2H), 2.86-3.05 (m, 1H), 3.60-3.75 (m, 1H), 3.85 (t, J=8.7 Hz, 1H), 4.22-4.38 (m, 2H), 4.69 (dd, J=12.0, 8.6 Hz, 1H), 4.95 (dd, J=12.0, 7.2 Hz, 1H), 4.98-5.09 (m, 2H), 5.26-5.42 (m, 1H), 6.48 (dd, J=16.1, 13.8 Hz, 1H), 6.62-6.68 (m, 1H), 6.96 (dd, J=15.5, 8.2 Hz, 1H), 7.16 (dd, J=16.1, 4.9 Hz, 1H), 7.35 (dd, J=8.5, 2.0 Hz, 1H), 7.64 (d, J=8.5 Hz, 1H), 7.81 (dd, J=8.5, 2.7 Hz, 1H), 8.09 (d, J=5.4 Hz, 1H), 8.13 (d, J=8.5 Hz, 1H). LCMS (m/z) 709.1, 711.1, 713.2 [M+H], Tr=2.38 min.
Reaction SMILES: [C:1]([OH:10])(=[O:9])[C:2]1[C:3](=[CH:5][CH:6]=[CH:7][CH:8]=1)[NH2:4].[C:11](OC(=O)C)(=O)[CH3:12].C(=O)(O)[O-].[Na+]>>[CH3:11][C:12]1[O:9][C:1](=[O:10])[C:2]2[CH:8]=[CH:7][CH:6]=[CH:5][C:3]=2[N:4]=1
Reactant: CC(=O)OC(C)=O
Reactant: Nc1ccccc1C(=O)O
Agent: O=C([O-])O
Agent: [Na+]
Product: Cc1nc2ccccc2c(=O)o1

Procedure:
4-iodo-2-methylbenzenamine 24 (233 mg, 1 mmol) on reaction with 2-ethynyl-6-methoxynaphthalene (25c, 182 mg, 1 mmol) by employing Sonagashira coupling conditions using Pd(PPh3)4 (69.3 mg, 0.06 equiv) as catalyst, CuI (22.8 mg, 0.12 equiv) as cocatalyst, butyl amine (261 mg, 3 equiv) as base and ether as solvent and kept the reaction for 6 h. After completion of the reaction as indicated by TLC and the reaction mixture is extracted into ether (4×25 mL) from the aqueous layer and concentrated in vacuo. The compound was further purified by column chromatography using 60-120 silica gel (ethyl acetate/hexane, 1:9) to obtain 4-((6-methoxynaphthalen-2-yl) ethynyl)-2-methyl benzenamine (26c) as pure product. Anthranilic acid (27, 137 mg, 1 mmol) on reaction with acetic anhydride at 150° C. and reflux for 30 min, after completion of reaction aqueous sodium bicarbonate solution is added and extracted in ethyl acetate (4×25 mL) from the aqueous layer and concentrated in vacuo afforded 2-methyl-4H-benzo[d][1,3]oxazin-4-one compound (28) as pure product. To a stirred solution of 4-((6-methoxynaphthalen-2-yl)ethynyl)-2-methylbenzenamine (26c) with 2-methyl-4H-benzo[d][1,3]oxazin-4-one (28, 161 mg, 1 mmol) in acetic acid and reflux for 8 h After completion of the reaction as indicated by TLC. then the reaction mixture was quenched with NaHCO3 and extracted in ethyl acetate (4×25 mL) from the ice cold aqueous layer and dried over anhydrous Na2SO4 afforded 3-(4-((6-methoxynaphthalen-2-yl)ethynyl)-2-methylphenyl)-2-methylquinazolin-4(3H)-one (29c). Reaction of 3-(4-((6-methoxynaphthalen-2-yl)ethynyl)-2-methylphenyl)-2-methylquinazolin-4(3H)-one (29c, 430 mg, 1 mmol) with 3,4,5-trimethoxybenzaldehyde (30l, 196 mg, 1 mmol) was taken in acetic acid Then the resulting mixture was stirred under reflux conditions for 8 h and then the reaction mixture was quenched with NaHCO3 and extracted in ethyl acetate (4×25 mL) from the ice cold aqueous layer and dried over anhydrous Na2SO4. The resulting product (61) was purified by column chromatography employing EtOAc/Hexane as an eluent.
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][C:7](=[O:11])[NH:8]2)=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Na+].[Na+].[C:18](OC([O-])=O)([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19]>C1COCC1>[C:21]([O:20][C:18]([N:8]1[C:9]2[C:5](=[CH:4][CH:3]=[C:2]([Cl:1])[CH:10]=2)[CH2:6][C:7]1=[O:11])=[O:19])([CH3:24])([CH3:23])[CH3:22]
Reactant: O=C1Cc2ccc(Cl)cc2N1
Reactant: CC(C)(C)OC(=O)OC(=O)[O-]
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N1C(=O)Cc2ccc(Cl)cc21
Temperature: 20 °C
Reaction time: 88 h
Yield: 48.3 %

Procedure:
A mixture of 6-chloro-1,3-dihydro-indol-2-one (11.35 g, 67.7 mmol), sodium carbonate (35.9 g, 338.5 mmol), tert-butyl dicarbonate (36.7 g, 168.2 mmol) and THF (300 mL) was stirred at 20° C. for 88 h then solids were removed by filtration and the filtrate evaporated in vacuo to give an oil. Chromatography (SiO2; gradient elution with 5-25% EtOAc in petrol) gave the title compound (8.746 g) as an oil. MS: [M−H]−=266.
Reaction SMILES: [N:1]1([C:6]2[CH:7]=[C:8]([CH:13]=[CH:14][CH:15]=2)[C:9]([O:11]C)=O)[CH:5]=[N:4][CH:3]=[N:2]1.[C:16]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])(=[O:18])[CH3:17].[Li]>>[C:20]([O:19][C:16](=[O:18])[CH2:17][C:9](=[O:11])[C:8]1[CH:13]=[CH:14][CH:15]=[C:6]([N:1]2[CH:5]=[N:4][CH:3]=[N:2]2)[CH:7]=1)([CH3:23])([CH3:22])[CH3:21]
Reactant: CC(=O)OC(C)(C)C
Reactant: COC(=O)c1cccc(-n2cncn2)c1
Agent: [Li]
Product: CC(C)(C)OC(=O)CC(=O)c1cccc(-n2cncn2)c1

Procedure:
Prepared from methyl 3-[1,2,4]triazol-1-yl-benzoate [CAS-No. 167626-27-9] by treatment with lithium tert.-butyl acetate according to general procedure H (method b). Obtained as an orange liquid (2.41 g).
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][CH:13]=[C:12]2[C:18](=O)[C:19](OC)=[O:20])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[BH4-].[Na+]>C(O)(C)C.O>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][CH:13]=[C:12]2[CH2:18][CH2:19][OH:20])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: COC(=O)C(=O)c1c[nH]c2ccc(OCc3ccccc3)cc12
Agent: [BH4-]
Agent: [Na+]
Solvent: O
Solvent: CC(C)O
Product: OCCc1c[nH]c2ccc(OCc3ccccc3)cc12

Procedure:
A suspension of methyl 5-benzyloxyindol-3-ylglyoxylate (10 g.) and sodium borohydride (3.7 g.) in isopropanol (100 ml.) was stirred and refluxed for 5 hours. The cooled mixture was diluted with water and extracted with dichloromethane. Evaporation of the extract gave a pale yellow oil which crystallised from a mixture of toluene and petroleum ether to give 5-benzyloxy-3-(2-hydroxyethyl)indole as a white crystalline powder m.p. 97°-98°.