Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: I[C:2]1[CH:3]=[C:4]([CH:30]=[CH:31][CH:32]=1)[C:5]([NH:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][C:15]2[C:20]([C:21]3[CH:26]=[CH:25][N:24]=[C:23]([NH:27][CH3:28])[N:22]=3)=[CH:19][CH:18]=[CH:17][N:16]=2)=[C:10]([CH3:29])[CH:9]=1)=[O:6].[CH3:33][N:34]([CH3:38])[CH2:35][C:36]#[CH:37]>C(N(CC)CC)C.C(#N)C.ClCCl.C1(C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)[Pd][P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[CH3:33][N:34]([CH3:38])[CH2:35][C:36]#[C:37][C:2]1[CH:3]=[C:4]([CH:30]=[CH:31][CH:32]=1)[C:5]([NH:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][C:15]2[C:20]([C:21]3[CH:26]=[CH:25][N:24]=[C:23]([NH:27][CH3:28])[N:22]=3)=[CH:19][CH:18]=[CH:17][N:16]=2)=[C:10]([CH3:29])[CH:9]=1)=[O:6]
Reactant: CNc1nccc(-c2cccnc2Oc2ccc(NC(=O)c3cccc(I)c3)cc2C)n1
Reactant: C#CCN(C)C
Agent: [Cu]I
Agent: c1ccc([P]([Pd][P](c2ccccc2)(c2ccccc2)c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: CC#N
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CNc1nccc(-c2cccnc2Oc2ccc(NC(=O)c3cccc(C#CCN(C)C)c3)cc2C)n1
Reaction time: 3.5 h

Procedure:
A mixture of 3-iodo-N-(3-methyl-4-(3-(2-(methylamino)pyrimidin-4-yl)pyridin-2-yloxy)phenyl)benzamide (0.20 g, 0.37 mmol), N,N-dimethylprop-2-yn-1-amine (0.080 mL, 0.74 mmol), bis(triphenylphosphine)palladium (II) dichloride (0.013 g, 0.020 mmol), copper (I) iodide (0.0035 g, 0.020 mmol) in triethylamine (1.5 mL) and acetonitrile (5 mL) was heated in a sealed tube to 100 deg. C. for 3.5 h. The reaction was diluted in dichloromethane and filtered. The filtrate was concentrated in vacuo and the resulting material was purified by silica gel chromatography using MeOH/dichloromethane as eluent to give 3-(3-(dimethylamino)prop-1-ynyl)-N-(3-methyl-4-(3-(2-(methylamino)pyrimidin-4-yl)pyridin-2-yloxy)phenyl)benzamide as a brown solid. MS m/z=493 [M+1]+. Calc'd for C29H28N6O2: 492.58.
Reaction SMILES: C(OP([CH2:9][C:10]([CH3:17])=[CH:11][C:12]([O:14][CH2:15][CH3:16])=[O:13])(OCC)=O)C.[Br:18][C:19]1[C:28]2[C:27]([CH3:30])([CH3:29])[CH2:26][CH:25]=[C:24]([CH:31]([CH2:33][CH3:34])[CH3:32])[C:23]=2[CH:22]=[C:21](/[C:35](/[CH2:40][CH3:41])=[C:36](/[F:39])\[CH:37]=O)[C:20]=1[O:42][CH2:43][CH3:44]>>[Br:18][C:19]1[C:28]2[C:27]([CH3:30])([CH3:29])[CH2:26][CH:25]=[C:24]([CH:31]([CH2:33][CH3:34])[CH3:32])[C:23]=2[CH:22]=[C:21](/[C:35](/[CH2:40][CH3:41])=[C:36](/[F:39])\[CH:37]=[CH:9]\[C:10](\[CH3:17])=[CH:11]\[C:12]([O:14][CH2:15][CH3:16])=[O:13])[C:20]=1[O:42][CH2:43][CH3:44]
Reactant: CCOC(=O)C=C(C)CP(=O)(OCC)OCC
Reactant: CCOc1c(/C(CC)=C(/F)C=O)cc2c(c1Br)C(C)(C)CC=C2C(C)CC
Product: CCOC(=O)/C=C(C)/C=C/C(F)=C(/CC)c1cc2c(c(Br)c1OCC)C(C)(C)CC=C2C(C)CC

Procedure:
Following General Procedure I-1, ethyl 4(diethoxyphosphoryl)-3-methyl-but-2-enoate (645 mg, 2.44 mmol) and (2E)-3-(4-Bromo-8-sec-butyl-3-ethoxy-5,5-dimethyl-5,6-dihydro-naphthalen-2-yl)-2-fluoro-pent-2-enal (Compound A-154, 333 mg, 0.81 mmol) were reacted to give the title compound as a light yellow syrup after purification by column chromatography (silica gel, 2% ethyl acetate in hexane).
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([S:8][CH2:9][CH3:10])=[CH:4][CH:3]=1.[Mn]([O-])(=O)(=O)=[O:12].[K+].[OH2:17]>C(O)(=O)C>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([CH2:9][CH3:10])(=[O:12])=[O:17])=[CH:4][CH:3]=1
Reactant: CCSc1ccc(Br)cc1
Reactant: O
Reactant: O=[Mn](=O)(=O)[O-]
Agent: [K+]
Solvent: CC(=O)O
Product: CCS(=O)(=O)c1ccc(Br)cc1
Temperature: 90 °C

Procedure:
1-Bromo-4-ethylsulfanyl-benzene (5.0 g) was dissolved in acetic acid and potassium permanganate as a 3% solution in water (8 mL) was added. The reaction mixture was heated to 90° C. for 3 hrs, after which time the reaction was cooled to room temperature and partitioned between ethyl acetate and 2N NaOH solution (500 m) each. The organics were separated and washed with water (100 mL), dried over sodium sulfate and purified on biotage eluting with 90:10 hexanes:ethyl acetate to afford the title compound as a clear oil (2.70 g). 1H NMR (300 MHz, CDCl3): δ 1.30 (t, J=7.85 Hz, 3 H) 3.02 (q, J=7.54 Hz, 2 H), 7.40 (m, 4 H).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[NH:8][C:9](=[O:26])[NH:10][C:11]1[CH:16]=[CH:15][C:14]([CH2:17][C:18]([O:20]C(C)(C)C)=[O:19])=[CH:13][C:12]=1[CH3:25].C(O)(C(F)(F)F)=O>C(Cl)Cl>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[NH:8][C:9](=[O:26])[NH:10][C:11]1[CH:16]=[CH:15][C:14]([CH2:17][C:18]([OH:20])=[O:19])=[CH:13][C:12]=1[CH3:25]
Reactant: Cc1cc(CC(=O)OC(C)(C)C)ccc1NC(=O)Nc1ccccc1Cl
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: Cc1cc(CC(=O)O)ccc1NC(=O)Nc1ccccc1Cl
Reaction time: 4 h
Yield: 99.6 %

Procedure:
To a stirred solution of tert-butyl 4-[N′-(2-chlorophenyl)ureido]-3-methylphenylacetate (1.57 g, 4.19 mmol) in CH2Cl2 (10 ml) was added TFA (6 ml) at room temperature. After 4 h stirring, the mixture was concentrated in vacuo. The residue was triturated by the addition of water to give 4-[N′-(2-chlorophenyl)ureido]-3-methylphenylacetic acid (1.33 g, 100%) as a yellow powder. mp 243-245° C. (dec.); 1H-NMR (CDCl3) δ2.24 (s, 3H), 3.47 (s, 2H), 6.99-7.08 (m, 3H), 7.28 (t, J=7.6 Hz, 1H), 7.44 (dt, J=8.0, 2.4 Hz, 1H), 7.66 (dd, J=8.3, 1.9 Hz, 1H), 8.13 (dd, J=6.1, 1.7 Hz, 1H), 8.61 (d, J=6.3 Hz, 2H); MS (ESI), m/z 319 (M++1), 321 (M++3); Anal. Calcd. for C16H15ClN2O3.0.7TFA: C, 59.33; H, 4.65; Cl, 10.85; N, 8.57. Found: C, 59.23; H, 4.64; Cl, 10.90; N, 8.40.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:27]=[C:28]([O:32][CH3:33])[C:29]=1[O:30][CH3:31])[CH2:6][N:7]1[C:11](=[O:12])[CH2:10][C:9]([CH2:20][CH2:21]OS(C)(=O)=O)([CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH2:8]1.[CH2:34]([O:36][CH2:37][CH2:38][N:39]1[C:43]2[CH:44]=[CH:45][CH:46]=[CH:47][C:42]=2[N:41]=[C:40]1[NH:48][CH:49]1[CH2:54][CH2:53][NH:52][CH2:51][CH2:50]1)[CH3:35]>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:27]=[C:28]([O:32][CH3:33])[C:29]=1[O:30][CH3:31])[CH2:6][N:7]1[C:11](=[O:12])[CH2:10][C:9]([CH2:20][CH2:21][N:52]2[CH2:51][CH2:50][CH:49]([NH:48][C:40]3[N:39]([CH2:38][CH2:37][O:36][CH2:34][CH3:35])[C:43]4[CH:44]=[CH:45][CH:46]=[CH:47][C:42]=4[N:41]=3)[CH2:54][CH2:53]2)([CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH2:8]1
Reactant: CCOCCn1c(NC2CCNCC2)nc2ccccc21
Reactant: COc1cc(CN2CC(CCOS(C)(=O)=O)(Cc3ccccc3)CC2=O)cc(OC)c1OC
Product: CCOCCn1c(NC2CCN(CCC3(Cc4ccccc4)CC(=O)N(Cc4cc(OC)c(OC)c(OC)c4)C3)CC2)nc2ccccc21

Procedure:
Prepare by the method of Example 1.6 using 1-(3,4,5-trimethoxybenzyl)-3-(2-methanesulfonyloxyethyl)-3-(phenylmethyl)-5-oxopyrrolidine (0.05 g, 0.10 mmol) and (1-(2-ethoxyethyl)-1H-benzimidazol-2-yl)(piperidin-4-yl)amine (0.03 g, 0.10 mmol). Purify by chromatography on silica gel eluting with 2% triethylamine/5% methanol/ethyl acetate to give the title compound: Rf=0.20 (silica gel, 2% triethylamine/5% methanol/ethyl acetate).
Reaction SMILES: [OH:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[O:5][C:4](=[O:12])[CH:3]=1.[C:13]1([CH:19](O)[CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.B(F)(F)F.CCOCC>O1CCOCC1>[C:13]1([CH:19]([C:3]2[C:4](=[O:12])[O:5][C:6]3[C:11]([C:2]=2[OH:1])=[CH:10][CH:9]=[CH:8][CH:7]=3)[CH2:20][C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: O=c1cc(O)c2ccccc2o1
Reactant: OC(Cc1ccccc1)c1ccccc1
Agent: FB(F)F
Solvent: C1COCCO1
Solvent: CCOCC
Product: O=c1oc2ccccc2c(O)c1C(Cc1ccccc1)c1ccccc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 8058.5 %

Procedure:
To a flame-dried flask containing a near-solution of 810 mg of 4-hydroxycoumarin and 1.20 mg of 1,2-diphenylethanol of Preparation 15 in 30 mL of dioxane under an argon atmosphere is added 3.0 mL of boron trifluoride etherate. The resulting yellow solution is left to stir at room temperature overnight; the reaction is then heated to reflux for 48 hours. The volatiles are removed and the residue is partioned between diethyl ether and 1N sodium hydroxide. The basic aqueous phase is washed with diethyl ether and acidified to pH=1 with 6N hydrochloric acid. The resulting precipitant is repeatedly extracted with dichloromethane (methanol-chloroform co-solvents). The combined dichloromethane extracts are washed once with dilute sodium bicarbonate to remove most of the unreacted 4-hydroxycoumarin, then brine, dried (magnesium sulfate), and finally concentrated under reduced pressure. The residue is adsorbed onto silica and flash column chromatographed with 40% to 50% ethyl acetate in hexanes to yield 167 mg of the title product as a white solid.
Reaction SMILES: C1(C)C=CC(S(O[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][C:26]([OH:28])=[O:27])(=O)=O)=CC=1.[C-:30]#[N:31].[Na+].C(OCC)C.O>CS(C)=O>[C:30]([CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][C:26]([OH:28])=[O:27])#[N:31]
Reactant: Cc1ccc(S(=O)(=O)OCCCCCCCCCCCCCCCC(=O)O)cc1
Reactant: [C-]#N
Agent: [Na+]
Solvent: CS(C)=O
Solvent: CCOCC
Solvent: O
Product: N#CCCCCCCCCCCCCCCCC(=O)O
Temperature: 80 °C
Reaction time: 5 h
Yield: 93.5 %

Procedure:
The methyl ester of 16-paratoluenesulfonyloxy-hexadecanoic acid (600 mg) was dissolved in dimethylsulfoxide (DMSO). Sodium cyanide (250 mg) was added to the solution, and the mixture was stirred at 80° C. for 5 hours. After the reaction mixture was cooled, it was distributed into diethyl ether and water. The diethyl ether layer is dried over anhydrous sodium sulfate and concentrated to give the methyl ester of 16-cyanohexadecanoic acid (370 mg). The product was dissolved in a mixed solvent of ethanol-water (1:1), and lithium hydroxide (180 mg) was added to the solution. The mixture was stirred at 80° C. for 30 minutes. The reaction mixture was cooled and ethanol was removed by distillation and extracted with ethyl acetate which had been adjusted to a weak acidic range of pH by adding citric acid. The ethyl acetate layer was dried and concentrated to give 16-cyanohexadecanoic acid (316 mg).
Reaction SMILES: [C:1]1([C:6]([C:8]2[CH:20]=[CH:19][C:11]([O:12][C:13]([CH3:18])([CH3:17])[C:14]([OH:16])=[O:15])=[CH:10][CH:9]=2)=[O:7])[S:5][CH:4]=[CH:3][CH:2]=1.S1C=CC=[C:22]1C(C1C=CC(O)=CC=1)=O.S(=O)(=O)(O)O>CO>[C:1]1([C:6]([C:8]2[CH:20]=[CH:19][C:11]([O:12][C:13]([CH3:17])([CH3:18])[C:14]([O:16][CH3:22])=[O:15])=[CH:10][CH:9]=2)=[O:7])[S:5][CH:4]=[CH:3][CH:2]=1
Reactant: CC(C)(Oc1ccc(C(=O)c2cccs2)cc1)C(=O)O
Reactant: O=C(c1ccc(O)cc1)c1cccs1
Agent: O=S(=O)(O)O
Solvent: CO
Product: COC(=O)C(C)(C)Oc1ccc(C(=O)c2cccs2)cc1

Procedure:
2-[4-(2-Thenoyl)-phenoxy]-2-methyl-propionic acid (M.p. 157° C.; 29 g; obtained according to the procedure described in Example 2 from 2-thienyl(4-hydroxy-phenyl)ketone) is dissolved in anhydrous methanol (300 ml), concentrated sulfuric acid (2 ml) is then added thereto and the mixture is heated for 6 hours at the reflux temperature. The solvent is then evaporated off under reduced pressure and the residue is dissolved in ethyl ether; the organic phase is washed with an aqueous sodium hydroxide solution. After neutralization and drying, the ether is evaporated off and the methyl ester is recrystallized from ethanol, to give 29 g of product which melts at 85° C.
Reaction SMILES: [CH3:1][C:2]([CH3:15])([CH3:14])[CH2:3][C:4]([C:6]1[CH:13]=[CH:12][C:9]([CH2:10]Br)=[CH:8][CH:7]=1)=[O:5].[C:16]1(=[O:26])[NH:20][C:19](=[O:21])[C:18]2=[CH:22][CH:23]=[CH:24][CH:25]=[C:17]12.[K]>CN(C=O)C.CCOC(C)=O>[CH3:1][C:2]([CH3:15])([CH3:14])[CH2:3][C:4]([C:6]1[CH:13]=[CH:12][C:9]([CH2:10][N:20]2[C:16](=[O:26])[C:17]3[C:18](=[CH:22][CH:23]=[CH:24][CH:25]=3)[C:19]2=[O:21])=[CH:8][CH:7]=1)=[O:5]
Reactant: O=C1NC(=O)c2ccccc21
Reactant: CC(C)(C)CC(=O)c1ccc(CBr)cc1
Agent: [K]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CC(C)(C)CC(=O)c1ccc(CN2C(=O)c3ccccc3C2=O)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 99.1 %

Procedure:
Add 4-(3,3-dimethyl-butyryl)-benzyl bromide (1 g, 3.731 mmol) to a stirred suspension of potassium phthalimide (0.705 g, 3.805 mmol) in anhydrous DMF (20 mL). Stir the mixture overnight at room temperature. Dilute with EtOAc and wash twice with ice-cold water. Dry the organic layer over Na2SO4, filter and concentrate in vacuo. Purify the crude mixture by chromatography on silica gel eluting sequentially with hexane and hexane/EtOAc (19:1, 4:1) to provide the desired intermediate as oil (1.24 g, 100%).
Reaction SMILES: [C:1]1([CH2:7][CH:8]=[CH:9][C:10]2[CH:11]=[C:12]([N+:16]([O-])=O)[CH:13]=[CH:14][CH:15]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.O.N.[S-][S-].[Na+].[Na+]>C(O)C>[C:1]1([CH2:7][CH:8]=[CH:9][C:10]2[CH:11]=[C:12]([CH:13]=[CH:14][CH:15]=2)[NH2:16])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: O=[N+]([O-])c1cccc(C=CCc2ccccc2)c1
Agent: N
Agent: [Na+]
Agent: [S-][S-]
Solvent: CCO
Solvent: O
Product: Nc1cccc(C=CCc2ccccc2)c1
Yield: 84.9 %

Procedure:
To a solution of 3-(3-phenyl-1-propenyl)nitrobenzene (10.5 g) in 200 ml of ethanol were added 70 ml of 35% ammonia water and 44 g of sodium disulfide. After heating under reflux for 2 hours, the solvent was removed under reduced pressure, followed by extraction with ethyl acetate. The extract was washed with water and dried over magnesium sulfate. The solvent was removed by distillation under reduced pressure to give 7.8 g of 3-(3-phenyl-1-propenyl)aniline (yield, 85%). B.P. 128°-130° C./0.09 mmHg.
Reaction SMILES: C1(S)C=CC=CC=1.[CH2:8]([NH2:11])[CH2:9][NH2:10].[CH3:12][CH2:13][CH:14]([CH2:16][CH:17]([CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][C:27]([NH:29][C@@H:30]1[C:61](=[O:62])[NH:60][C@@H:59]([C@H:63]([OH:65])[CH3:64])[C:57](=[O:58])[N:56]2[C@@H:52]([CH2:53][C@@H:54]([OH:66])[CH2:55]2)[C:50](=[O:51])[NH:49][C@@H:48]([C@H:67]([OH:77])[C@@H:68]([OH:76])[C:69]2[CH:74]=[CH:73][C:72]([OH:75])=[CH:71][CH:70]=2)[C:46](=[O:47])[NH:45][C@@H:44]([C@H:78]([OH:83])[CH2:79][C:80]([NH2:82])=O)[C:42](=[O:43])[N:41]2[C@@H:37]([C@@H:38]([OH:84])[CH2:39][CH2:40]2)[C:35](=[O:36])[NH:34][C@H:33](O)[C@H:32]([OH:86])[CH2:31]1)=[O:28])[CH3:18])[CH3:15]>>[CH3:12][CH2:13][CH:14]([CH2:16][CH:17]([CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][C:27]([NH:29][C@@H:30]1[C:61](=[O:62])[NH:60][C@@H:59]([C@H:63]([OH:65])[CH3:64])[C:57](=[O:58])[N:56]2[C@@H:52]([CH2:53][C@@H:54]([OH:66])[CH2:55]2)[C:50](=[O:51])[NH:49][C@@H:48]([C@H:67]([OH:77])[C@@H:68]([OH:76])[C:69]2[CH:74]=[CH:73][C:72]([OH:75])=[CH:71][CH:70]=2)[C:46](=[O:47])[NH:45][C@@H:44]([C@H:78]([OH:83])[CH2:79][CH2:80][NH2:82])[C:42](=[O:43])[N:41]2[C@@H:37]([C@@H:38]([OH:84])[CH2:39][CH2:40]2)[C:35](=[O:36])[NH:34][C@H:33]([NH:10][CH2:9][CH2:8][NH2:11])[C@H:32]([OH:86])[CH2:31]1)=[O:28])[CH3:18])[CH3:15]
Reactant: CCC(C)CC(C)CCCCCCCCC(=O)N[C@H]1C[C@@H](O)[C@@H](O)NC(=O)[C@@H]2[C@@H](O)CCN2C(=O)[C@H]([C@H](O)CC(N)=O)NC(=O)[C@H]([C@H](O)[C@@H](O)c2ccc(O)cc2)NC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@H]([C@@H](C)O)NC1=O
Reactant: NCCN
Agent: Sc1ccccc1
Product: CCC(C)CC(C)CCCCCCCCC(=O)N[C@H]1C[C@@H](O)[C@@H](NCCN)NC(=O)[C@@H]2[C@@H](O)CCN2C(=O)[C@H]([C@H](O)CCN)NC(=O)[C@H]([C@H](O)[C@@H](O)c2ccc(O)cc2)NC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@H]([C@@H](C)O)NC1=O

Procedure:
According to WO96/24613 and US5552521, the primary amide group in Pneumocandin B0 is reduced to amine group (47% of yield), and then the resulting product reacts with thiophenol and ethylenediamine in turn to obtain caspofungin.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[C:15](=[O:19])[N:14]([CH2:20][CH:21]([CH3:23])[CH3:22])[C:13]([C:24]([O:26][CH3:27])=[O:25])=[C:12]2OS(C(F)(F)F)(=O)=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:36][C:37]1[CH:42]=[CH:41][C:40](B(O)O)=[CH:39][CH:38]=1.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.CO.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>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[C:15](=[O:19])[N:14]([CH2:20][CH:21]([CH3:23])[CH3:22])[C:13]([C:24]([O:26][CH3:27])=[O:25])=[C:12]2[C:40]1[CH:41]=[CH:42][C:37]([F:36])=[CH:38][CH:39]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: OB(O)c1ccc(F)cc1
Reactant: COC(=O)c1c(OS(=O)(=O)C(F)(F)F)c2cc(OCc3ccccc3)ccc2c(=O)n1CC(C)C
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: Cc1ccccc1
Solvent: O
Solvent: CO
Product: COC(=O)c1c(-c2ccc(F)cc2)c2cc(OCc3ccccc3)ccc2c(=O)n1CC(C)C
Yield: 74.9 %

Procedure:
A mixed solution of methyl 6-benzyloxy-2-isobutyl-1-oxo-4-trifluoromethanesulfonyloxy-1,2-dihydro-3-isoquinolinecarboxylate (7.70 g, 15 mmol), 4-fluorophenylboronic acid (2.52 g, 18 mmol) and sodium carbonate (3.97 g, 37.5 mmol) in toluene (50 mL), methanol (10 mL) and water (10 mL) was stirred under an argon atmosphere at room temperature for 30 min. To the obtained mixture was added tetrakis(triphenylphosphine)palladium (0.87 g, 0.9 mmol) and the mixture was refluxed under heating under an argon atmosphere for 12 h. The reaction mixture was poured into water and extracted with ethyl acetate. After washing the extract with water, the extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to give methyl 6-benzyloxy-4-(4-fluorophenyl)-2-isobutyl-1-oxo-1,2-dihydro-3-isoquinolinecarboxylate (5.16 g, 74.9%) as crystals.
Reaction SMILES: [C:1]([C:3]1[N:4]=[C:5]([CH2:19][OH:20])[NH:6][C:7]=1[C:8]1[C:9]([CH3:18])=[CH:10][C:11]([CH3:17])=[C:12]([CH:16]=1)[C:13]([OH:15])=O)#[N:2].CC1NC(C2C=C(C=CC=2C)C(O)=O)=C(C)N=1.Cl.[F:39][C:40]1([C:44]2[CH:51]=[CH:50][C:47]([C:48]#[N:49])=[CH:46][CH:45]=2)[CH2:43][NH:42][CH2:41]1.Cl.N1CC(C2C=CC(C#N)=CC=2)C1>>[C:48]([C:47]1[CH:50]=[CH:51][C:44]([C:40]2([F:39])[CH2:43][N:42]([C:13]([C:12]3[C:11]([CH3:17])=[CH:10][C:9]([CH3:18])=[C:8]([C:7]4[NH:6][C:5]([CH2:19][OH:20])=[N:4][C:3]=4[C:1]#[N:2])[CH:16]=3)=[O:15])[CH2:41]2)=[CH:45][CH:46]=1)#[N:49]
Reactant: N#Cc1ccc(C2(F)CNC2)cc1
Reactant: Cc1cc(C)c(-c2[nH]c(CO)nc2C#N)cc1C(=O)O
Agent: Cc1nc(C)c(-c2cc(C(=O)O)ccc2C)[nH]1
Agent: Cl
Agent: N#Cc1ccc(C2CNC2)cc1
Product: Cc1cc(C)c(-c2[nH]c(CO)nc2C#N)cc1C(=O)N1CC(F)(c2ccc(C#N)cc2)C1

Procedure:
The title compound was prepared using standard chemical manipulations and procedures similar to those used for the preparation of compound 5, except 5-(4-cyano-2-(hydroxymethyl)-1H-imidazol-5-yl)-2,4-dimethylbenzoic acid (compound 219.6) was used in place of 3-(2,4-dimethyl-1H-imidazol-5-yl)-4-methylbenzoic acid (compound 5.7) and 4-(3-fluoroazetidin-3-yl)benzonitrile hydrochloride (compound 43.4) was used in place of 4-(azetidin-3-yl)benzonitrile hydrochloride (compound 5.2). m/z (ES+) 430 (M+H)+.
Reaction SMILES: [Cl:1][C:2]1[C:7]([CH2:8][NH2:9])=[CH:6][CH:5]=[CH:4][N:3]=1.[C:10](OC(=O)C)(=[O:12])[CH3:11].C(N(CC)CC)C>ClCCl>[Cl:1][C:2]1[C:7]([CH2:8][NH:9][C:10](=[O:12])[CH3:11])=[CH:6][CH:5]=[CH:4][N:3]=1
Reactant: NCc1cccnc1Cl
Reactant: CC(=O)OC(C)=O
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(=O)NCc1cccnc1Cl
Yield: 47.5 %

Procedure:
To a solution of (2-chloro-3-pyridyl)methanamine (300 mg, 2.10 mmol) in dichloromethane (2 mL) at room temperature is added acetic acid anhydride (198.88 mL, 2.10 mmol) and triethylamine (293.26 mL, 2.10 mmol). After 1 h the reaction is quenched with saturated aqueous solution of sodium bicarbonate and extracted with dichloromethane. The organic layer was separated, dried over magnesium sulfate and the solvent evaporated in vacuo to afford 184 mg of N-[(2-chloro-3-pyridyl)methyl]acetamide. MS (m/z): 185 (M+1)
Reaction SMILES: [CH2:1]([N:8]=[C:9]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[CH3:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1(P(C2C=CC=CC=2)CCCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(O)(=O)C.[H][H]>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.C1(C)C=CC=CC=1>[CH2:1]([NH:8][CH:9]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[CH3:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CC(=NCc1ccccc1)c1ccccc1
Reactant: [H][H]
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [I-]
Agent: c1ccc(P(CCCCP(c2ccccc2)c2ccccc2)c2ccccc2)cc1
Solvent: Cc1ccccc1
Solvent: CC(=O)O
Product: CC(NCc1ccccc1)c1ccccc1
Reaction time: 2 h

Procedure:
The process is carried out as in Example 8 but the reaction conditions are modified as follows: 0.636 g (4.8 mmol) of N-benzyl-N-(1-phenylethylidene)amine, 3.2 mg (0.0048 mmol) of [Ir(1,5-cyclooctadiene)Cl]2, 4.5 mg (0.01 mmol) of 1,4-bis(diphenylphosphino)butane (ligand) and 30 mg (0.08 mmol) of tetrabutylammonium iodide, 2 ml of acetic acid, 5 ml of toluene, 40 bar of hydrogen, reaction temperature: 25° C. The reaction time is 2 hours, the conversion is complete.
Reaction SMILES: Br[CH:2]([CH3:10])[C:3](=O)[CH2:4][C:5]([O:7][CH3:8])=[O:6].[C:11]([NH2:19])(=[O:18])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1>>[CH3:10][C:2]1[O:18][C:11]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[N:19][C:3]=1[CH2:4][C:5]([O:7][CH3:8])=[O:6]
Reactant: COC(=O)CC(=O)C(C)Br
Reactant: NC(=O)c1ccccc1
Product: COC(=O)Cc1nc(-c2ccccc2)oc1C

Procedure:
reacting methyl 4-bromo-3-oxovalerate with benzamide to give methyl 2-(5-methyl-2-phenyl-4-oxazolyl)acetate, or reacting ethyl 4-bromo-3-oxovalerate with benzamide to give ethyl 2-(5-methyl-2-phenyl-4-oxazolyl)acetate,
Reaction SMILES: [C:1]([C:3]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[NH:5][CH:4]=1)#[N:2].C([S:14]P(CC)(=S)O)C.[ClH:20]>C(OCC)(=O)C>[ClH:20].[NH:5]1[C:6]2[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=2)[C:3]([C:1](=[S:14])[NH2:2])=[CH:4]1
Reactant: CCSP(O)(=S)CC
Reactant: N#Cc1c[nH]c2ccccc12
Agent: Cl
Solvent: CCOC(C)=O
Product: NC(=S)c1c[nH]c2ccccc12

Procedure:
To a solution of 1.0 g of 3-cyanoindole in 30 ml of ethyl acetate was added 1.1 ml of diethyldithiophosphonic acid. The solution was then saturated with gaseous hydrogen chloride and stirred at room temperature for 18 hours. The thioamide was isolated from the reaction mixture as a tan precipitate and used directly in the following reaction.
Reaction SMILES: [CH2:1]([C:15]1[CH:27]=[CH:26][C:18]([N:19]([CH2:23][CH2:24][OH:25])[CH2:20][CH2:21][OH:22])=[CH:17][CH:16]=1)[C:2]1[CH:14]=[CH:13][C:5]([N:6]([CH2:10][CH2:11][OH:12])[CH2:7][CH2:8][OH:9])=[CH:4][CH:3]=1.[S].[NH3:29].[Cl-:30].[NH4+]>C(O)(C)C.C(OCC)C.C(O)CO>[ClH:30].[C:1]([C:15]1[CH:16]=[CH:17][C:18]([N:19]([CH2:23][CH2:24][OH:25])[CH2:20][CH2:21][OH:22])=[CH:26][CH:27]=1)([C:2]1[CH:3]=[CH:4][C:5]([N:6]([CH2:10][CH2:11][OH:12])[CH2:7][CH2:8][OH:9])=[CH:13][CH:14]=1)=[NH:29]
Reactant: [Cl-]
Reactant: N
Reactant: OCCN(CCO)c1ccc(Cc2ccc(N(CCO)CCO)cc2)cc1
Agent: [NH4+]
Agent: [S]
Solvent: OCCO
Solvent: CCOCC
Solvent: CC(C)O
Product: Cl
Product: N=C(c1ccc(N(CCO)CCO)cc1)c1ccc(N(CCO)CCO)cc1
Temperature: 140 °C
Reaction time: 16 h

Procedure:
A mixture of 486.8 grams (1.3 moles) of 4,4'-methylenebis[N,N-bis(2-hydroxyethyl)aniline], 230 grams (7.2 moles) of sulfur and 800 grams of ethylene glycol was heated at 140° C. for 4 hours while a stream of ammonia gas was bubbled therein. To the reaction mixture was then added 170 grams (3.2 moles) of ammonium chloride and heating at 140° C. was continued for an additional 16 hours. The reaction mixture was cooled to 60° C., diluted with 3 liters of isopropanol, and added to diethyl ether to precipitate the dye. The dye was recovered by filtration, dissolved in 70° C. water and salted out by adding sodium chloride thereto. The resulting product was recovered and dried in vacuo. The dried tar was dissolved in 500 mls. of N,N-dimethylformamide, treated with activated carbon, filtered and precipitated by adding the filtrate to diethyl ether. This was repeated using 500 mls. of methanol. The resulting oil was recovered and triturated with isopropanol and diethyl ether to effect crystallization. The crystals were dried in vacuo to obtain 95 grams of product, which was found to be pure by thin layer chromatography.