Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[O:7][CH2:8][CH:9]=[CH:10][N:11]1[C:16]([OH:17])=[C:15]2[CH:18]=[C:19]([NH:21][C:22](=[O:27])[C:23]([CH3:26])([CH3:25])[CH3:24])[N:20]=[C:14]2[N:13]=[CH:12]1.I[C:29]1[CH:50]=[CH:49][C:32]([C:33]([NH:35][C@H:36]([C:44]([O:46][CH2:47][CH3:48])=[O:45])[CH2:37][CH2:38][C:39]([O:41][CH2:42][CH3:43])=[O:40])=[O:34])=[CH:31][CH:30]=1.CC1C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.IC1C=CC(C(N[C@H](C(OCC)=O)CCC([O-])=O)=O)=CC=1>C(N(CC)CC)C.C(#N)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[O:7][CH2:8][C:9]([C:29]1[CH:50]=[CH:49][C:32]([C:33]([NH:35][C@H:36]([C:44]([O:46][CH2:47][CH3:48])=[O:45])[CH2:37][CH2:38][C:39]([O:41][CH2:42][CH3:43])=[O:40])=[O:34])=[CH:31][CH:30]=1)=[CH:10][N:11]1[C:16]([OH:17])=[C:15]2[CH:18]=[C:19]([NH:21][C:22](=[O:27])[C:23]([CH3:24])([CH3:26])[CH3:25])[N:20]=[C:14]2[N:13]=[CH:12]1
Reactant: CCOC(=O)CC[C@H](NC(=O)c1ccc(I)cc1)C(=O)OCC
Reactant: CC(C)(C)C(=O)Nc1cc2c(O)n(C=CCOC3CCCCO3)cnc-2n1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: CCOC(=O)[C@H](CCC(=O)[O-])NC(=O)c1ccc(I)cc1
Solvent: CC#N
Solvent: CCN(CC)CC
Product: CCOC(=O)CC[C@H](NC(=O)c1ccc(C(=Cn2cnc3nc(NC(=O)C(C)(C)C)cc-3c2O)COC2CCCCO2)cc1)C(=O)OCC
Reaction time: 12 h

Procedure:
A mixture containing 3.48 g of 3-(3-tetrahydropyr-2-yloxyprop-1-en-1-yl)-4-hydroxy-6-pivaloylaminopyrrolo[2,3-d]pyrimidine, 3.12g (1.2 equiv.) of diethyl N-(4-iodobenzoyl)glutamate, 546 mg (20%) of tris-(2-methylphenyl)phosphine, 201 mg (10%) of palladium acetate and 85.5 mg (5%) of cuprous iodide in 15 ml of triethylamine and 240 ml of acetonitrile is heated at reflux under nitrogen. After 12 hours., 1.17 g of ethyl N-(4-iodobenzoyl)glutamate are added and the reaction mixture is heated at reflux under nitrogen for an additional 12 hours. The reaction mixture then is concentrated under reduced pressure and the residue chromatographed on silica gel, eluting with 20:1 ethyl acetate:hexane. (Any recovered starting material can be recycled through the foregoing procedure.) The concentrated material is dissolved in 1:5 ethyl acetate:ether and this solution is refrigerated for 15 hours. The solid which forms is collected by filtration, washed with cold ethyl acetate and dried to yield diethyl N-[4-{1-(tetrahydropyr-2-yloxy)-3-(4-hydroxy-6-pivaloylaminopyrrolo[2,3-d]pyrimidin-3-yl)prop-2-en-2yl}benzoyl]glutamate.
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[C:13]([NH:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[CH3:21])=[C:12]([F:22])[C:8]2[NH:9][CH:10]=[N:11][C:7]=2[CH:6]=1)=[O:4].C1COCC1.CO.C1C(=O)N([Br:37])C(=O)C1.CC1C=CC(S(O)(=O)=O)=CC=1.O>CO>[CH3:1][O:2][C:3]([C:5]1[C:13]([NH:14][C:15]2[CH:20]=[CH:19][C:18]([Br:37])=[CH:17][C:16]=2[CH3:21])=[C:12]([F:22])[C:8]2[NH:9][CH:10]=[N:11][C:7]=2[CH:6]=1)=[O:4]
Reactant: O=C1CCC(=O)N1Br
Reactant: COC(=O)c1cc2nc[nH]c2c(F)c1Nc1ccccc1C
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: C1CCOC1
Solvent: CO
Solvent: O
Product: COC(=O)c1cc2nc[nH]c2c(F)c1Nc1ccc(Br)cc1C
Temperature: -78 °C
Reaction time: 0.5 h
Yield: 79.2 %

Procedure:
7-Fluoro-6-o-tolylamino-1H-benzoimidazole-5-carboxylic acid methyl ester 7a (2.00 g, 6.68 mmol) is suspended in 1:1 THF/MeOH (60 mL) and cooled to −78° C. under a nitrogen atmosphere. A solution of NBS (1.20 g, 6.75 mmol) in 1:1 THF/MeOH (5 mL) is added followed by a MeOH (5 mL) solution of TsOH.H2O (1.9 g, 10.0 mmol). After 30 minutes, the reaction mixture is warmed to 0° C. and then after 1 hour warmed to room temperature. After 16 hours, more NBS (0.12 g, 0.67 mmol) is added and the reaction mixture is allowed to stir for 3 hours. The reaction mixture is quenched by the addition of 10% Na2S2O4 solution. After 30 minutes, the reaction mixture is diluted with water and ethyl acetate and the layers separated. The aqueous layer is extracted with ethyl acetate. The combined organic extracts are dried (Na2SO4) and concentrated under reduced pressure. The recovered solid is triturated with methylene chloride to give 2.00 g (79%) pure desired product: MS APCI (+) m/z 380, 378 (M+1 Br pattern) detected.
Reaction SMILES: Br[CH2:2][C:3]1[C:12]([Cl:13])=[N:11][CH:10]=[CH:9][C:4]=1[C:5]([O:7]C)=O.Cl.[F:15][C:16]([F:30])([CH:27]([F:29])[F:28])[CH2:17][O:18][C:19]1[N:24]=[CH:23][C:22]([CH2:25][NH2:26])=[CH:21][CH:20]=1>>[Cl:13][C:12]1[C:3]2[CH2:2][N:26]([CH2:25][C:22]3[CH:23]=[N:24][C:19]([O:18][CH2:17][C:16]([F:30])([F:15])[CH:27]([F:29])[F:28])=[CH:20][CH:21]=3)[C:5](=[O:7])[C:4]=2[CH:9]=[CH:10][N:11]=1
Reactant: NCc1ccc(OCC(F)(F)C(F)F)nc1
Reactant: COC(=O)c1ccnc(Cl)c1CBr
Agent: Cl
Product: O=C1c2ccnc(Cl)c2CN1Cc1ccc(OCC(F)(F)C(F)F)nc1
Yield: 60 %

Procedure:
The title compound is prepared in 60% yield (132 mg, white solid) from methyl 3-(bromomethyl)-2-chloroisonicotinate (150 mg, 0.57 mmol) and (6-(2,2,3,3-tetrafluoropropoxy)pyridin-3-yl)methanamine hydrochloride (156 mg, 0.57 mmol, Amine-14) in a similar manner to Intermediate-2.
Reaction SMILES: C(OC([NH:8][C:9]1[C:10]([CH3:17])=[N:11][S:12][C:13]=1[C:14]([OH:16])=[O:15])=O)(C)(C)C.O1CCOCC1>Cl>[NH2:8][C:9]1[C:10]([CH3:17])=[N:11][S:12][C:13]=1[C:14]([OH:16])=[O:15]
Reactant: Cc1nsc(C(=O)O)c1NC(=O)OC(C)(C)C
Agent: Cl
Solvent: C1COCCO1
Product: Cc1nsc(C(=O)O)c1N
Temperature: 25 °C
Reaction time: 8 h

Procedure:
4-tert-Butoxycarbonylamino-3-methyl-isothiazole-5-carboxylic acid (method 56) (11 g, 45 mmol) was dissolved in 50 mL of 4M solution of HCl in 1,4-dioxane (200 mmol) and the resulting solution was stirred at room temperature overnight. The TLC showed the complete disappearance of the starting acid. The reaction was concentrated and the residue was triturated with ether and the precipitated hydrochloride salt was filtered off and washed with ether and dried to provide the product as a light brown powder. Yield 8.2 g (100%). 1H NMR (300 MHz, DMSO-d6) δ 2.30 (s, 3H), 8.85 (bs, 3H).
Reaction SMILES: [CH:1]1([CH2:7][CH2:8][CH2:9][C@@H:10]([C:19]2[O:23][N:22]=[C:21]([CH2:24][C:25]3[CH:26]=[N:27][CH:28]=[CH:29][CH:30]=3)[N:20]=2)[CH2:11][C:12]([O:14]C(C)(C)C)=[O:13])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1>Cl.O1CCOCC1>[CH:1]1([CH2:7][CH2:8][CH2:9][C@@H:10]([C:19]2[O:23][N:22]=[C:21]([CH2:24][C:25]3[CH:26]=[N:27][CH:28]=[CH:29][CH:30]=3)[N:20]=2)[CH2:11][C:12]([OH:14])=[O:13])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: CC(C)(C)OC(=O)C[C@@H](CCCC1CCCCC1)c1nc(Cc2cccnc2)no1
Agent: Cl
Solvent: C1COCCO1
Product: O=C(O)C[C@@H](CCCC1CCCCC1)c1nc(Cc2cccnc2)no1
Temperature: 25 °C
Reaction time: 24 h
Yield: 118.1 %

Procedure:
A solution of tert-butyl (3R)-6-cyclohexyl-3-[3-(3-pyridinylmethyl)-1,2,4-oxadiazol-5-yl]hexanoate (Preparation 108) (408 mg, 0.99 mmol) in hydrogen chloride in 1,4-dioxan (4M) (5 ml) was stirred at room temperature for 18 hours. T.l.c. analysis showed reaction had gone >90%. A couple of drops of concentrated hydrochloric acid were added and the reaction mixture was stirred at room temperature for a further 24 hours. The solvent was removed under reduced pressure. A fresh portion of hydrogen chloride in 1,4-dioxan (4M) (4 ml) was added and stirred at room temperature for 4 hours. The solvent was removed under reduced pressure and azeotroped with ethyl acetate and diethylether. The oil was dried under reduced pressure to afford the title compound as a yellow oil (418 mg).
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][C:13]([C:18]([N:20]1[CH2:25][CH2:24][N:23]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=3[C:32]([CH3:35])([CH3:34])[CH3:33])[CH2:22][CH2:21]1)=[O:19])=[CH:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.IC.[H-].[Na+].[CH3:40]N(C)C=O>O>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[N:14]([CH3:40])[C:13]([C:18]([N:20]1[CH2:25][CH2:24][N:23]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=3[C:32]([CH3:35])([CH3:34])[CH3:33])[CH2:22][CH2:21]1)=[O:19])=[CH:12]2)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CC(C)(C)c1ccccc1N1CCN(C(=O)c2cc3cc(OCc4ccccc4)ccc3[nH]2)CC1
Reactant: CN(C)C=O
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CI
Product: Cn1c(C(=O)N2CCN(c3ccccc3C(C)(C)C)CC2)cc2cc(OCc3ccccc3)ccc21
Temperature: 25 °C
Reaction time: 16 h
Yield: 95 %

Procedure:
A mixture of 5-(benzyloxy)-2-{[4-(2-tert-butylphenyl)piperazin-1-yl]carbonyl}-1H-indole obtained in Example 23 (880 mg), iodomethane (0.143 mL), sodium hydride (92 mg, 60% in oil dispersion), and N,N-dimethylformamide (5 mL) was stirred at room temperature for 16 h. Water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure to provide the title compound (860 mg, 95%) as crystals.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][C:13](=[O:18])[CH2:12]2)=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH:19]1[C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[CH:21]=[C:20]1[CH:28]=O>C(O)C.N1CCCCC1>[C:1]([O:5][C:6]([NH:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][C:13](=[O:18])[C:12]2=[CH:28][C:20]1[NH:19][C:27]2[C:22]([CH:21]=1)=[CH:23][CH:24]=[CH:25][CH:26]=2)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: O=Cc1cc2ccccc2[nH]1
Reactant: CC(C)(C)OC(=O)Nc1ccc2c(c1)CC(=O)N2
Solvent: CCO
Solvent: C1CCNCC1
Product: CC(C)(C)OC(=O)Nc1ccc2c(c1)C(=Cc1cc3ccccc3[nH]1)C(=O)N2
Temperature: 90 °C
Yield: 104.5 %

Procedure:
A mixture of 5-tert-butoxycarbonylamino-2-oxindole (124 mg), indole-2-carbaldehyde (87 mg) (prepared according to Synthetic Communications, 1993, 23, 3109) and piperidine (4 mg) in ethanol (2 mL was heated in a sealed tube at 90° C. for 3 hours. The mixture was cooled to room temperature. The solid was collected by vacuum filtration, washed with cold ethanol and dried in oven for overnight to give 196 mg of 5-tert-butoxycarbonylamino-3-(1H-indol-2-ylmethylene)-1,3-dihydro-indol-2-one as a bright orange solid. It was then dissolved in trifluoroacetic acid/dichloromethane mixture (2 mL each) and stirred at room temperature for 1 hour. The reaction mixture was concentrated. The residue was dissolved in water and basified with saturated sodium bicarbonate solution. The solid was collected by vacuum filtration, washed with water and dried in vacuum oven for overnight to give 129 mg of 5-amino-3-(1H-indol-2-ylmethylene)-1,3-dihydro-indol-2-one as a brown solid.
Reaction SMILES: Br[C:2]1[CH:3]=[CH:4][C:5]2[O:11][CH2:10][CH2:9][N:8]([CH2:12][C:13]3[N:18]=[CH:17][CH:16]=[CH:15][N:14]=3)[C:7](=[O:19])[C:6]=2[CH:20]=1.[F:21][C:22]1[CH:23]=[C:24](B2OC(C)(C)C(C)(C)O2)[CH:25]=[CH:26][C:27]=1[C:28]([F:31])([F:30])[F:29].C(=O)([O-])[O-].[Cs+].[Cs+].CCOC(C)=O>CN(C=O)C.O.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].Cl[Pd]Cl>[F:21][C:22]1[CH:23]=[C:24]([C:2]2[CH:3]=[CH:4][C:5]3[O:11][CH2:10][CH2:9][N:8]([CH2:12][C:13]4[N:18]=[CH:17][CH:16]=[CH:15][N:14]=4)[C:7](=[O:19])[C:6]=3[CH:20]=2)[CH:25]=[CH:26][C:27]=1[C:28]([F:29])([F:30])[F:31]
Reactant: O=C1c2cc(Br)ccc2OCCN1Cc1ncccn1
Reactant: CC1(C)OB(c2ccc(C(F)(F)F)c(F)c2)OC1(C)C
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: O=C([O-])[O-]
Solvent: O
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: O=C1c2cc(-c3ccc(C(F)(F)F)c(F)c3)ccc2OCCN1Cc1ncccn1
Temperature: 85 °C

Procedure:
A mixture of 7-bromo-4-(pyrimidin-2-ylmethyl)-3,4-dihydrobenzo[f][1,4]oxazepin-5(2H)-one (50 mg, 0.15 mmol), 2-(3-fluoro-4-(trifluoromethyl)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (52 mg, 0.18 mmol), cesium carbonate (146 mg, 0.45 mmol), 1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium (10 mg, 0.015 mmol) was dissolved in a degassed mixture of DMF and water 3/1.5 (4.5 mL). The mixture was heated in microwave at 85° C. for 40 min. The mixture was poured into EtOAc and washed with water and brine. The organic layer was collected, dried over sodium sulfate and loaded onto silica gel. A flash column (5% MeOH in EtOAc) and reverse phase chromatography gave 7-(3-fluoro-4-(trifluoromethyl)phenyl)-4-(pyrimidin-2-ylmethyl)-3,4-dihydrobenzo[f][1,4]oxazepin-5 (2H)-one.
Reaction SMILES: [CH3:1][C:2]1([CH3:14])[CH2:10][CH2:9][CH:8]2[C:11](=[CH2:12])[CH:3]1[CH2:4][CH2:5][CH:6]([OH:13])[CH2:7]2.[C:15](OC(=O)C)(=[O:17])[CH3:16].O>P(=O)(O)(O)O.CCOCC>[C:15]([O:13][CH:6]1[CH2:5][CH2:4][CH:3]2[C:11](=[CH2:12])[CH:8]([CH2:9][CH2:10][C:2]2([CH3:14])[CH3:1])[CH2:7]1)(=[O:17])[CH3:16]
Reactant: CC(=O)OC(C)=O
Reactant: C=C1C2CCC(C)(C)C1CCC(O)C2
Agent: O=P(O)(O)O
Solvent: O
Solvent: CCOCC
Product: C=C1C2CCC(C)(C)C1CCC(OC(C)=O)C2
Temperature: 25 °C
Reaction time: 8 h

Procedure:
In a 3-necked flask which was equipped with a reflux condenser, there were placed, under N2 -atmosphere, 0.9 g (4.6 mmoles) of 7,7-dimethyl-10-methylene-bicyclo[4.3.1] decan-3-ol, 8 ml of acetic anhydride and 1 drop of phosphoric acid. The reaction mixture was stirred overnight at room temperature. Then 50 ml of H2O were added and the solution stirred one more night at room temperature. The resulting mixture was taken up in ether, washed to neutrality with brine and dried over Na2SO4. After filtration and concentration in vacuo, the product was distilled in a bulb-to-bulb apparatus at 150° C. (10 Pa). There were obtained 1.09 g of a colorless oil in 99% of the theoretical yield. The thus-obtained mixture was composed of 2 isomers (71/29) which were separated by gas chromatography on a chemically insert CARBOWAX® column having a length of 5 meters.
Reaction SMILES: [NH2:1][C:2]1[N:6]([C:7]2[CH:12]=[C:11]([S:13][CH2:14][C:15]([F:18])([F:17])[F:16])[C:10]([CH3:19])=[CH:9][C:8]=2[F:20])[N:5]=[C:4]([O:21][CH2:22][C:23]([F:32])([F:31])[C:24]([F:30])([F:29])[C:25]([F:28])([F:27])[F:26])[CH:3]=1.[C:33](OC(=O)C)(=[O:35])C>C(O)=O>[F:20][C:8]1[CH:9]=[C:10]([CH3:19])[C:11]([S:13][CH2:14][C:15]([F:17])([F:18])[F:16])=[CH:12][C:7]=1[N:6]1[C:2]([NH:1][CH:33]=[O:35])=[CH:3][C:4]([O:21][CH2:22][C:23]([F:32])([F:31])[C:24]([F:30])([F:29])[C:25]([F:26])([F:27])[F:28])=[N:5]1
Reactant: CC(=O)OC(C)=O
Reactant: Cc1cc(F)c(-n2nc(OCC(F)(F)C(F)(F)C(F)(F)F)cc2N)cc1SCC(F)(F)F
Solvent: O=CO
Product: Cc1cc(F)c(-n2nc(OCC(F)(F)C(F)(F)C(F)(F)F)cc2NC=O)cc1SCC(F)(F)F
Temperature: 25 °C
Reaction time: 12 h

Procedure:
1.18 g of 5-amino-1-{2-fluoro-4-methyl-5-(2,2,2-trifluoroethylthio)phenyl}-3-(2,2,3,3,4,4,4-heptafluorobutoxy)pyrazole was dissolved in 15 mL of formic acid, and 8mL of acetic anhydride was added under cooling with ice, followed by stirring at room temperature for 12 hours. Then, extraction with ethyl acetate was carried out, the organic layer was dried over anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure, and the obtained residue was purified by column chromatography (developing solvent ethyl acetate:hexane=1:2) to obtain 0.92 g of 1-{2-fluoro-4-methyl-5-(2,2,2-trifluoroethylthio)phenyl}-5-formylamino-3-(2,2,3,3,4,4,4-heptafluorobutoxy)pyrazole.
Reaction SMILES: [NH2:1][CH2:2][CH2:3][C:4]1[CH:9]=[CH:8][C:7]([NH:10][C:11](=[O:26])[CH2:12][C:13]2[N:14]=[C:15]([NH:18][CH2:19][C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[S:16][CH:17]=2)=[CH:6][CH:5]=1.[O:27]([CH2:34][C@@H:35]1[CH2:37][O:36]1)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1>CC(O)C>[CH2:19]([NH:18][C:15]1[S:16][CH:17]=[C:13]([CH2:12][C:11]([NH:10][C:7]2[CH:8]=[CH:9][C:4]([CH2:3][CH2:2][NH:1][CH2:37][C@H:35]([OH:36])[CH2:34][O:27][C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)=[CH:5][CH:6]=2)=[O:26])[N:14]=1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1
Reactant: c1ccc(OC[C@@H]2CO2)cc1
Reactant: NCCc1ccc(NC(=O)Cc2csc(NCc3ccccc3)n2)cc1
Solvent: CC(C)O
Product: O=C(Cc1csc(NCc2ccccc2)n1)Nc1ccc(CCNC[C@H](O)COc2ccccc2)cc1
Yield: 26.5 %

Procedure:
A solution of 670 mg of N-[4-(2-aminoethyl)phenyl]-2-(2-benzylaminothiazol-4-yl)acetamide and 300 mg of (S)-2-[(phenoxy)methyl]oxirane in 20 ml of 2-propanol was heated under refluxing for three hours. The solvent was evaporated off in vacuo and the residue was purified by means of silica gel column chromatography (eluate: chloroform/methanol=10/1). The resulting solid was recrystallized from methanol to obtain 250 mg of (S)-2-(2-benzylamino-4-thiazolyl)-4′-[2-[(2-hydroxy-3-phenoxypropyl)amino]ethyl]acetanilide.
Reaction SMILES: [Cl:1][C:2]1[C:7]([Cl:8])=[C:6](I)[CH:5]=[CH:4][N:3]=1.[CH3:10][C:11]1[CH:16]=[CH:15][C:14](B(O)O)=[CH:13][CH:12]=1.C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.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:1][C:2]1[C:7]([Cl:8])=[C:6]([C:14]2[CH:15]=[CH:16][C:11]([CH3:10])=[CH:12][CH:13]=2)[CH:5]=[CH:4][N:3]=1
Reactant: Cc1ccc(B(O)O)cc1
Reactant: Clc1nccc(I)c1Cl
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
Product: Cc1ccc(-c2ccnc(Cl)c2Cl)cc1
Temperature: 100 °C
Yield: 98.4 %

Procedure:
To a solution of 2,3-dichloro-4-iodopyridine (1.92 g, 7.0 mmol) in toluene (20 mL) at room temperature under argon was added 4-methylphenylboronic acid (1.05 g, 7.7 mmol), tetrakis(triphenylphosphine)palladium (0.40 g, 0.35 mmol), and aqueous Na2CO3 solution (2.0 M, 7 mL, 14 mmol). The resulting suspension was stirred and heated at 100° C. under argon for 5 h. Analysis by HPLC/MS indicated that starting material had been consumed. After the reaction mixture was cooled to room temperature, water (25 mL) and EtOAc (30 mL) were added. The layers were separated. The organic layer was dried (Na2SO4), filtered, and concentrated under reduced pressure. The crude product was purified by automated silica gel chromatography (eluted with ethyl acetate-hexanes) to obtain 1.64 g of the title compound as a white solid. HPLC/MS: retention time=3.77 min, [M+H]+=238. 1H NMR (CDCl3): δ 8.30 (d, J=4.9 Hz, 1H), 7.34-7.29 (m, 4H), 7.20 (d, J=4.9 Hz, 1H), 2.43 (s, 3H).
Reaction SMILES: [CH2:1]1[O:13][C:12]2[CH:11]=[C:10]3[C:5]([CH2:6][CH2:7][CH2:8][C:9]3=O)=[CH:4][C:3]=2[O:2]1.[H-].[Al+3].[Li+].[H-].[H-].[H-].[OH-].[Na+].[SH:23][CH2:24][C:25]([OH:27])=[O:26]>O1CCCC1.C1C=CC=CC=1.C(Cl)(Cl)Cl.O>[CH2:1]1[O:13][C:12]2[CH:11]=[C:10]3[C:5]([CH2:6][CH2:7][CH2:8][CH:9]3[S:23][CH2:24][C:25]([OH:27])=[O:26])=[CH:4][C:3]=2[O:2]1
Reactant: O=C1CCCc2cc3c(cc21)OCO3
Reactant: O=C(O)CS
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: ClC(Cl)Cl
Solvent: c1ccccc1
Solvent: O
Product: O=C(O)CSC1CCCc2cc3c(cc21)OCO3
Temperature: 25 °C
Reaction time: 8 h
Yield: 83.3 %

Procedure:
1.2 g of 6,7-methylenedioxy-1-tetralone was added to a suspension of 0.2 g of lithium aluminum hydride in 20 ml of tetrahydrofuran under cooling with ice. The mixture was stirred at room temperature overnight and cooled with ice/water. 0.2 ml of water, then 0.2 ml of a 15% aqueous sodium hydroxide solution and finally 0.6 ml of water were added thereto. Insoluble substances were removed by filtration. The filtrate was concentrated to obtain a crystalline residue. 1.1 g of mercaptoacetic acid and a catalytic amount of D-10-camphosulfonic acid were added to the residue and the mixture was heated in 30 ml of benzene under reflux for 1 h. The reaction mixture was washed with water. After extraction with a 1Naqueous sodium hydroxide solution, the aqueous layer was acidified with 1N hydrochloric acid. After extraction with chloroform, the extract was dried over magnesium sulfate and the solvent was distilled off. The crystalline residue thus obtained was treated according to silica gel column chromatography (chloroform) to obtain 1.4 g of the intended compound in the form of white crystals.
Reaction SMILES: [CH2:1]([NH2:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:9](Br)[CH:10]=[CH2:11].C(=O)(O)[O-].[Na+]>CS(C)=O.[I-].[Na+]>[C:2]1([CH2:1][NH:8][CH2:11][CH:10]=[CH2:9])[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: C=CCBr
Reactant: NCc1ccccc1
Agent: O=C([O-])O
Agent: [I-]
Agent: [Na+]
Solvent: CS(C)=O
Product: C=CCNCc1ccccc1
Temperature: 25 °C
Reaction time: 3 h
Yield: 56.2 %

Procedure:
To a solution of benzylamine (5.7 ml, 52.2 mmol) and sodium iodide (38 mg, 0.25 mmol) in DMSO (30 ml) was added dropwise allyl bromide (2.2 ml, 25.4 mmol) at 0° C. under argon. After stirring for 3 h at room temperature the reaction was complete as shown by TLC (cyclohexanes:ethyl acetate 1:1). Then saturated aqueous sodium bicarbonate solution was added, the product was extracted with diethyl ether (100 ml) and the organic layer was washed with brine. The crude product was purified via flash chromatography to give the title compound (2.1 g, 57%) as a clear oil. 1H NMR (400 MHz, CDCl3) δ (ppm): 7.4-7.2 (m, 5H), 6.0-5.9 (m, 1H), 5.3-5.1 (m, 2H), 3.8 (s, 2H), 3.3 (d, 2H), 1.5 (bs, 1H).
Reaction SMILES: [N:1]1[CH:6]=[CH:5][C:4]([NH:7][C:8]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[NH:10][C:9]=2[C:17]([OH:19])=[O:18])=[CH:3][CH:2]=1.[C:20]([O:25][CH3:26])(=[O:24])[C@H:21]([CH3:23])O.CN1CCOCC1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>CCOCC.CC#N.CN(C=O)C>[CH3:26][O:25][C:20]([C@@H:21]([O:18][C:17]([C:9]1[NH:10][C:11]2[C:16]([C:8]=1[NH:7][C:4]1[CH:5]=[CH:6][N:1]=[CH:2][CH:3]=1)=[CH:15][CH:14]=[CH:13][CH:12]=2)=[O:19])[CH3:23])=[O:24]
Reactant: O=C(O)c1[nH]c2ccccc2c1Nc1ccncc1
Reactant: COC(=O)[C@H](C)O
Agent: CN(C)[P+](On1nnc2ccccc21)(N(C)C)N(C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CC#N
Solvent: CN1CCOCC1
Product: COC(=O)[C@H](C)OC(=O)c1[nH]c2ccccc2c1Nc1ccncc1
Temperature: 0 °C

Procedure:
Stir at 0° C. a mixture of 3-(4-pyridinylamino)-1H-indole-2-carboxylic acid (3.0 g, 12 mmol), methyl (S)-(−)-lactate (2.3 mL, 24 mmol), 4-methylmorpholine (2.6 mL,24 mmol) and DMF (50.0 mL). Add benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (BOP, 5.32 g, 12 mmol) in one portion and stir at ambient temperature overnight. Add brine (50 mL) and extract with ethyl acetate (3×200 mL). Concentrate under vacuum to an oil. Chromatograph over silica gel (5 g) and elute with dichloromethane, EtOAC, and MeOH. Concentrate like fractions under vacuum to an oil. Treat the oil with HCl in ether (10 mL) add additional ether (50 mL) and concentrate under vacuum to an oil. Treat the oil with 5% aqueous NaHCO3 and extract with EtOAc. Dry the extract over Na2SO4, filter and concentrate to an oil. Scratch the oil with a glass rod in the presence of ether to obtain a sticky solid. Add CH3CN and then ether and obtain of the title compound as a yellow solid, 140 mg: MS 340(M+H), Rt=2.73 min. (95/5/0.1 (A) 5/95/0.1 (B) Water/CAN/Formic Acid YMC ODS-A 2×50 mm 1 mL/min Gradient Composition: 100% A for 0.1 min Linear Gradient to 100% B at 2 min Hold until 3.5 min.)