Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3](=[O:31])[CH2:4][C:5]1[CH:10]=[C:9]([C:11]2[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][CH:12]=2)[N:8]=[C:7]([C:21]2[CH:26]=[CH:25][C:24]([C:27]([F:30])([F:29])[F:28])=[CH:23][CH:22]=2)[CH:6]=1.C[Si]([N-][Si](C)(C)C)(C)C.[K+].Br[CH2:43][C:44]([CH3:46])=[CH2:45]>C1COCC1>[CH3:1][O:2][C:3](=[O:31])[CH:4]([C:5]1[CH:6]=[C:7]([C:21]2[CH:26]=[CH:25][C:24]([C:27]([F:30])([F:28])[F:29])=[CH:23][CH:22]=2)[N:8]=[C:9]([C:11]2[CH:12]=[CH:13][C:14]([C:17]([F:18])([F:19])[F:20])=[CH:15][CH:16]=2)[CH:10]=1)[CH2:45][C:44]([CH3:46])=[CH2:43]
Reactant: C=C(C)CBr
Reactant: COC(=O)Cc1cc(-c2ccc(C(F)(F)F)cc2)nc(-c2ccc(C(F)(F)F)cc2)c1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [K+]
Solvent: C1CCOC1
Product: C=C(C)CC(C(=O)OC)c1cc(-c2ccc(C(F)(F)F)cc2)nc(-c2ccc(C(F)(F)F)cc2)c1
Reaction time: 0.5 h
Yield: 70.8 %

Procedure:
To a solution of [2,6-bis-(4-trifluoromethylphenyl)-pyridin-4-yl]-acetic acid methyl ester (1.18 g, 2.69 mmol) in THF (30 mL) at −78° C. under argon was added potassium bis(trimethylsilyl)amide (0.5 M solution in toluene, 5.38 mL, 2.69 mmol). After stirring for 30 minutes, 3-bromo-2-methylpropene (273 μL, 2.69 mmol) was added and stirred for an additional 30 minutes. The reaction mixture was allowed to warm up slowly and stirred for another 30 minutes at 0° C. The mixture was then concentrated and purified by column chromatography on silica gel (0-8% ethyl acetate in heptane) to give the product as a white solid (940 mg, 71%). 1H NMR (300 MHz, CDCl3) δ 8.24 (d, J=8.29 Hz, 4H), 7.76 (d, J=8.29 Hz, 4H), 7.74 (s, 2H), 4.79 (d, J=19.59 Hz, 2H), 3.97 (dd, J=6.78, 9.04 Hz, 1H), 3.72 (s, 3H), 2.95 (dd, J=8.85, 14.51 Hz, 1H), 2.56 (dd, J=6.59, 14.51 Hz, 1H), 1.78 (s, 3H). MS m/e 494.2 (M+H)
Reaction SMILES: Br[C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[CH:5][NH:6]2.[CH3:11][O:12][C:13]1[CH:14]=[C:15](B(O)O)[CH:16]=[CH:17][C:18]=1[O:19][CH3:20].O1CCCC1>C(=O)([O-])[O-].[K+].[K+].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>[CH3:11][O:12][C:13]1[CH:14]=[C:15]([C:2]2[CH:10]=[CH:9][CH:8]=[C:7]3[C:3]=2[CH:4]=[CH:5][NH:6]3)[CH:16]=[CH:17][C:18]=1[O:19][CH3:20]
Reactant: Brc1cccc2[nH]ccc12
Reactant: COc1ccc(B(O)O)cc1OC
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: C1CCOC1
Product: COc1ccc(-c2cccc3[nH]ccc23)cc1OC
Temperature: 100 °C

Procedure:
In a microwave safe tube, 4-Bromoindole (1.383 g, 0.007054 mol), 3,4-dimethoxyphenyl boronic acid (3.21 g, 0.0176 mol), and Tetrakis(triphenylphosphine)palladium(0) (0.41 g, 0.00035 mol) were mixed in 1.00 M of Potassium carbonate in Water (21 mL) and Tetrahydrofuran (34 mL, 0.42 mol). The resulting mixture was heated at 100° Celsius in the microwave for 10 minutes. The reaction mixture was partitioned between water and ethyl acetate. The aqueous layer was extracted with ethyl acetate and the organic layers were combined, washed with brine and dried over sodium sulfate. The reaction mixture was concentrated under reduced pressure and the residue was purified by silica gel chromatography (30% ethyl acetate in hexanes) to the yield 1.02 g of the titled compound as a light green solid. MS(ESI) [M+H+]+=254.20.
Reaction SMILES: [CH:1]1([C:7]2[C:8]3[CH:9]=[CH:10][C:11]([C:27]([O:29][CH3:30])=[O:28])=[CH:12][C:13]=3[N:14]3[C:21]=2[C:20]2[CH:22]=[CH:23][CH:24]=[CH:25][C:19]=2[O:18][CH2:17][C:16](=O)[CH2:15]3)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:31][N:32]1[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[OH-].[Na+]>C(Cl)Cl.CCOC(C)=O>[CH:1]1([C:7]2[C:8]3[CH:9]=[CH:10][C:11]([C:27]([O:29][CH3:30])=[O:28])=[CH:12][C:13]=3[N:14]3[C:21]=2[C:20]2[CH:22]=[CH:23][CH:24]=[CH:25][C:19]=2[O:18][CH2:17][CH:16]([N:35]2[CH2:36][CH2:37][N:32]([CH3:31])[CH2:33][CH2:34]2)[CH2:15]3)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: CN1CCNCC1
Reactant: COC(=O)c1ccc2c(C3CCCCC3)c3n(c2c1)CC(=O)COc1ccccc1-3
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Agent: [OH-]
Solvent: CC(=O)O
Solvent: ClCCl
Solvent: CCOC(C)=O
Product: COC(=O)c1ccc2c(C3CCCCC3)c3n(c2c1)CC(N1CCN(C)CC1)COc1ccccc1-3
Reaction time: 0.08 h

Procedure:
To a solution of methyl 14-cyclohexyl-7-oxo-7,8-dihydro-6H-indolo[1,2-e][1,5]benzoxazocine-11-carboxylate (prepared as described in Example 9, Step 4) in DCM (0.04 M), were added 3.0 eq of 1-methylpiperazine and 4.5 eq acetic acid, followed by 1.5 eq. of solid sodium triacetoxyborohydride. NaOH (20 eq, 1 N) was added after 2 h, and after stirring for 5 min the mixture was taken into EtOAc and washed with water and brine. Drying over sodium sulfate and concentration in vacuo gave the crude product, which was used without any further purification; MS (ES+) m/z 488 (M+H)+.
Reaction SMILES: C1C=C[NH+]=CC=1.Br[Br-]Br.[F:10][C:11]1[CH:32]=[CH:31][C:14]([CH2:15][N:16]2[C:28]3[CH2:27][CH2:26][CH2:25][C:24](=[O:29])[C:23]=3[C:22]3[C:17]2=[CH:18][CH:19]=[C:20]([CH3:30])[CH:21]=3)=[CH:13][CH:12]=1.[Br-].[Li+].C(=O)([O-])[O-].[Li+].[Li+]>C1COCC1.CN(C=O)C>[F:10][C:11]1[CH:32]=[CH:31][C:14]([CH2:15][N:16]2[C:28]3[CH:27]=[CH:26][CH:25]=[C:24]([OH:29])[C:23]=3[C:22]3[C:17]2=[CH:18][CH:19]=[C:20]([CH3:30])[CH:21]=3)=[CH:13][CH:12]=1
Reactant: Cc1ccc2c(c1)c1c(n2Cc2ccc(F)cc2)CCCC1=O
Agent: O=C([O-])[O-]
Agent: [Br-]
Agent: [Li+]
Solvent: CN(C)C=O
Solvent: C1CCOC1
Product: Cc1ccc2c(c1)c1c(O)cccc1n2Cc1ccc(F)cc1
Temperature: 75 °C
Reaction time: 6 h
Yield: 7.9 %

Procedure:
Pyridinium bromide perbromide (0.8153 g, 0.0026 mol) is added to a mixture of 9-(4-fluorobenzyl)-6-methyl-1,2,3,9-tetrahydro-4H-carbazol-4-one (0.6351 g, 0.0021 mol) in dry THF (4.2 mL) and dry DMF (3 mL) and the mixture is heated to 75° C. After stirring for 6 h, additional pyridinium bromide perbromide (0.0951 g, 0.30 mmol) is added and the mixture is stirred another hour. After storing in the freezer overnight, the mixture is again heated for another 40 min. THF is removed under reduced pressure and the residue is partitioned between dichloromethane and brine. The combined organic layers are washed with dilute sodium thiosulfate/brine and the aqueous layer is backwashed with dichloromethane. The combined organic layers are dried over magnesium sulfate and concentrated to dryness. The residue is combined with lithium bromide (0.4092 g, 0.0047 mol), lithium carbonate (0.3652 g, 0.0049 mol) and dry DMF (12 mL) and heated at 120° C. for 1.5 h. DMF is removed under high vacuum and the mixture is partitioned between dichloromethane and water. The combined organic layers are dried over sodium sulfate and concentrated to dryness. The residue is chromatographed on silica gel (100 mL) using hexane (100%, to remove oil from sample) followed by ethyl acetate (100%). The residue is chromatographed again on silica gel (125 mL) using ethyl acetate/heptane (10/90) to give 0.0505 g (8%) of the title compound; MS (ESI−) for C20H16FNO m/z 304.1 (M−H)−; 1H NMR (CDCl3) δ2.54, 5.33, 5.43, 6.57, 6.93, 7.08, 7.24, 8.12.
Reaction SMILES: [CH3:1][C:2]1[S:3][C:4]([C:8]([OH:10])=O)=[C:5]([CH3:7])[N:6]=1.CN(C)C=O.C(Cl)([Cl:18])=O>C1(C)C=CC=CC=1>[CH3:1][C:2]1[S:3][C:4]([C:8]([Cl:18])=[O:10])=[C:5]([CH3:7])[N:6]=1
Reactant: O=C(Cl)Cl
Reactant: Cc1nc(C)c(C(=O)O)s1
Solvent: Cc1ccccc1
Solvent: CN(C)C=O
Product: Cc1nc(C)c(C(=O)Cl)s1

Procedure:
In a similar apparatus to Example 1, 15.7 g (0.1 mole) of 2,4-dimethylthiazole-5-carboxylic acid were suspended in 100 ml of toluene, followed by the addition of 0.1 g of N,N-dimethylformamide. Under heating and reflux, phosgene was blown at a rate of 1.3 l/hr for 5 hours (0.29 mole). After completion of the reaction, the reaction mixture was filtered and the filtrate was concentrated to obtain 17.2 g of 2,4-dimethylthiazole-5-carboxylic acid chloride. Its purity and yield were 97.5% and 98.0%, respectively.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH3:11])[CH:5]=[C:6]([N+:8]([O-])=O)[CH:7]=1.[Sn].O.O.[Cl-].[Cl-]>C(O)C.[OH-].[Na+]>[Cl:1][C:2]1[CH:7]=[C:6]([CH:5]=[C:4]([CH3:11])[CH:3]=1)[NH2:8]
Reactant: Cc1cc(Cl)cc([N+](=O)[O-])c1
Agent: [Cl-]
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Product: Cc1cc(N)cc(Cl)c1

Procedure:
2.4 g of 3-chloro-5-nitro-toluene are dissolved in 35 ml of ethanol, combined with 15.8 g tin dichloride-dihydrate and refluxed for 3 hours. The solvent is eliminated in vacuo, the residue is taken up in 4 M sodium hydroxide solution and filtered through kieselguhr. The filter cake is washed thoroughly with ethyl acetate. The aqueous phase is extracted 3 times with ethyl acetate and the combined organic phases are washed with saturated sodium chloride solution and dried on magnesium sulphate. The solvent is eliminated in vacuo and the residue is chromatographed on silica gel (cyclohexane/ethyl acetate 81:15 to 70:30).
Reaction SMILES: [CH3:1][N:2]1[CH2:7][CH2:6][CH2:5][C@@H:4]([O:8][C:9]2[C:17]3[C:16]4[CH:18]=[C:19]([C:22]#[N:23])[N:20]=[CH:21][C:15]=4[N:14](COCC[Si](C)(C)C)[C:13]=3[N:12]=[CH:11][CH:10]=2)[CH2:3]1.Br.[OH-].[Na+].Cl>O1CCOCC1>[CH3:1][N:2]1[CH2:7][CH2:6][CH2:5][C@@H:4]([O:8][C:9]2[C:17]3[C:16]4[CH:18]=[C:19]([C:22]#[N:23])[N:20]=[CH:21][C:15]=4[NH:14][C:13]=3[N:12]=[CH:11][CH:10]=2)[CH2:3]1
Reactant: CN1CCC[C@@H](Oc2ccnc3c2c2cc(C#N)ncc2n3COCC[Si](C)(C)C)C1
Agent: Br
Agent: Cl
Agent: [Na+]
Solvent: C1COCCO1
Product: CN1CCC[C@@H](Oc2ccnc3[nH]c4cnc(C#N)cc4c23)C1
Temperature: 75 °C
Yield: 27.9 %

Procedure:
(R)-4-(1-methylpiperidin-3-yloxy)-9-(2-trimethylsilanyl-ethoxymethyl)-9H-dipyrido[2,3-b;4′,3′-d]pyrrole-6-carbonitrile (93 mg, 0.21 mmol) was dissolved in 1,4-dioxane (0.5 mL) and then treated with 48% HBr(aq) (0.5 mL) and heated at 75° C. for 15 minutes. The cooled reaction mixture was then basified to pH ˜12 by dropwise addition of 6N sodium hydroxide and then immediately acidified to pH ˜8-9 by dropwise addition of concentrated hydrochloric acid, producing a cloudy precipitate. The solid was collected by centrifugation, dissolved in dimethylsulfoxide (2 mL), and purified by preparative HPLC [5-85% methanol in water (0.1% ammonium hydroxide) over 30 min, 35 mL/min] to afford the title compound as a white solid (18 mg, 27%). 1H NMR (400 MHz, d6-DMSO) δ 12.74 (s, 1H), 8.96 (d, J=0.8, 1H), 8.52 (d, J=5.8, 1H), 8.46 (d, J=0.9, 1H), 7.10 (d, J=5.9, 1H), 4.93-4.82 (m, 1H), 2.93 (m, 1H), 2.57-2.51 (m, 1H), 2.44 (m, 1H), 2.24 (s, 3H), 2.19 (m, 1H), 2.08 (m, 1H), 1.83 (m, 1H), 1.68 (m, 2H). LCMS (Method D): RT=7.08 min, M+H+=308.1.
Reaction SMILES: [C:1]([N:20]1[CH2:34][CH2:33][CH:32]([OH:35])[C@H:21]1[C:22]([O:24][CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)=[O:23])([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C[N+]1([O-])CCOCC1>C(Cl)Cl.[Ru]([O-])(=O)(=O)=O.C([N+](CCC)(CCC)CCC)CC>[C:1]([N:20]1[CH2:34][CH2:33][C:32](=[O:35])[C@H:21]1[C:22]([O:24][CH2:25][C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1)=[O:23])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)([C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1
Reactant: O=C(OCc1ccccc1)[C@@H]1C(O)CCN1C(c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=[Ru](=O)(=O)[O-]
Agent: CCC[N+](CCC)(CCC)CCC
Agent: C[N+]1([O-])CCOCC1
Solvent: ClCCl
Product: O=C1CCN(C(c2ccccc2)(c2ccccc2)c2ccccc2)[C@@H]1C(=O)OCc1ccccc1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 74.1 %

Procedure:
To a solution of N-trityl-3-hydroxy-(L)-proline, benzyl ester (8.8 g, 19 mmol) in CH2Cl2 (50 mL) was added 4-methylmorpholine N-oxide (4.5 g, 38 mmol) and 3Å molecular sieves (3 g). After stirring at rt for 15 min, the reaction mixture was cooled to 0° C., and was added tetrapropylammonium perruthenate (1.0 g, 2.8 mmol). After stirring at rt for 15 min, the reaction mixture was filtered through a pad of silica gel, and the filtrate was concentrated in vacuo to dryness. The residue was dissolved in Et2O (100 mL), and was filtered through a pad of silica gel. The filtrate was concentrated in vacuo to dryness to yield N-trityl-3-keto-(L)-proline, benzyl ester (6.5 g, 74%).
Reaction SMILES: [Cl:1][C:2]1[C:3]([N+:13]([O-])=O)=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][C:6]([CH3:12])=[CH:5]2.Cl>CO.[Fe]>[Cl:1][C:2]1[C:3]([NH2:13])=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][C:6]([CH3:12])=[CH:5]2
Reactant: Cc1cnc2ccc(Cl)c([N+](=O)[O-])c2c1
Agent: [Fe]
Agent: Cl
Solvent: CO
Product: Cc1cnc2ccc(Cl)c(N)c2c1
Temperature: 50 °C
Yield: 84.7 %

Procedure:
To a solution of 6-chloro-3-methyl-5-nitroquinoline (6.70 g, 30.1 mmol) in methanol (45 mL) was added iron powder (5.55 g, 99.3 mmol), followed by careful addition of a concentrated aqueous HCl solution (15.6 mL). The resulting reaction mixture was heated for 1 h at 50° C. and concentrated at reduced pressure using a rotary evaporator. The residue was dissolved in water and basified (pH=9) using a 33% aqueous ammonia solution. The resulting brown suspension was extracted twice with EtOAc and the combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated at reduced pressure to afford the title compound as a brown solid (4.92 g, 25.5 mmol, 85%). 1H NMR (400 MHz, CDCl3, 298 K): δ=8.75 (s, 1H), 7.93 (s, 1H), 7.53 (d, J=9.0 Hz, 1H), 7.50 (d, J=9.0 Hz, 1H), 2.56 (s, 3H). MS (ES+): 193 (M(C10H935ClN2)+H)+.
Reaction SMILES: [Cl:1][C:2]1[C:3]2[CH:11]=[CH:10][NH:9][C:4]=2[N:5]=[C:6]([CH3:8])[N:7]=1.[I:12]N1C(=O)CCC1=O>ClCCl>[Cl:1][C:2]1[C:3]2[C:11]([I:12])=[CH:10][NH:9][C:4]=2[N:5]=[C:6]([CH3:8])[N:7]=1
Reactant: Cc1nc(Cl)c2cc[nH]c2n1
Reactant: O=C1CCC(=O)N1I
Solvent: ClCCl
Product: Cc1nc(Cl)c2c(I)c[nH]c2n1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a solution of 4-chloro-2-methyl-7H-pyrrolo[2,3-d]pyrimidine (400 mg, 2.4 mmol) in dichloromethane (10 mL) was added N-iodosuccinimide (537 mg, 2.39 mmol). The mixture was stirred at room temperature for 2 hours, then washed with aqueous sodium sulfite solution, dried over sodium sulfate, filtered, and concentrated in vacuo to provide the product as a brown solid. Yield: 330 mg, 1.12 mmol, 47%. LCMS m/z 293.8[M+H+].
Reaction SMILES: [CH:1]([CH:4]1[C:9](=[O:10])[NH:8][CH:7]=[CH:6][S:5]1)([CH3:3])[CH3:2].[H-].[Na+].Br[CH2:14][C:15]([O:17][CH3:18])=[O:16].O>O1CCCC1>[CH:1]([CH:4]1[C:9](=[O:10])[N:8]([CH2:14][C:15]([O:17][CH3:18])=[O:16])[CH:7]=[CH:6][S:5]1)([CH3:3])[CH3:2]
Reactant: COC(=O)CBr
Reactant: CC(C)C1SC=CNC1=O
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Product: COC(=O)CN1C=CSC(C(C)C)C1=O
Temperature: 25 °C
Reaction time: 0.17 h

Procedure:
A solution of (2RS)-2-isopropyl-3,4-dihydro-2H-1,4-thiazin-3-one (70 mg, Reference compound No. 42-1) in anhydrous tetrahydrofuran (1 ml) is added to a solution of sodium hydride (39 mg) in anhydrous tetrahydrofuran (1 ml) under ice cooling, and the mixture is stirred for 10 minutes. Methyl bromoacetate (74.3 mg) is added to the mixture, the temperature is raised to room temperature, and the whole is stirred for 20 minutes. The reaction mixture is cooled with ice, water is added to the mixture, and the whole is extracted with ethyl acetate. The extract is washed with 1 N hydrochloric acid, water and saturated brine successively and dried over anhydrous magnesium sulfate. The extract is concentrated under reduced pressure, and the resulting residue is purified by silica gel column chromatography to give the titled reference compound (90.2 mg).
Reaction SMILES: [CH2:1]1[O:8][CH:2]1[CH2:3][CH2:4][CH2:5][CH2:6][CH3:7].[CH2:9]([NH2:17])[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][NH2:16]>>[CH2:9]([NH:17][CH2:1][CH:2]([OH:8])[CH2:3][CH2:4][CH2:5][CH2:6][CH3:7])[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][NH:16][CH2:1][CH:2]([OH:8])[CH2:3][CH2:4][CH2:5][CH2:6][CH3:7]
Reactant: NCCCCCCCN
Reactant: CCCCCC1CO1
Product: CCCCCC(O)CNCCCCCCCNCC(O)CCCCC

Procedure:
Condensation of 1-heptene oxide and 1,7-heptanediamine affords N,N'-(1,7-heptylene)-bis[2-hydroxyheptylamine] (I: R= CH3 (CH2)4, R' = H, X= (CH2)7, Z= H).
Reaction SMILES: [NH2:1][C:2]1[CH:12]=[C:11]([C:13]([CH3:16])([CH3:15])[CH3:14])[C:5]2[O:6][CH2:7][C:8]([CH3:10])([CH3:9])[C:4]=2[CH:3]=1.CN(C1C=CC=CN=1)C.[C:26](Cl)(=[O:28])[CH3:27].CCCCCC>C(Cl)Cl.CCOCC.CCOC(C)=O>[C:13]([C:11]1[C:5]2[O:6][CH2:7][C:8]([CH3:10])([CH3:9])[C:4]=2[CH:3]=[C:2]([NH:1][C:26](=[O:28])[CH3:27])[CH:12]=1)([CH3:16])([CH3:15])[CH3:14]
Reactant: CC(=O)Cl
Reactant: CC(C)(C)c1cc(N)cc2c1OCC2(C)C
Agent: CN(C)c1ccccn1
Solvent: CCCCCC
Solvent: CCOC(C)=O
Solvent: ClCCl
Product: CC(=O)Nc1cc(C(C)(C)C)c2c(c1)C(C)(C)CO2
Reaction time: 1 h

Procedure:
To a solution of 5-amino-7-tert-butyl-3,3-dimethyl-2,3-dihydrobenzo[b]-furan (400 mg, 1.84 mmol) and dimethylaminopyridine (247 mg, 2.024 mmol) in CH2Cl2 (20 mL) is added at 24° C. acetyl chloride (130 μL, 1.84 mmol) in a single portion. The reaction is stirred for 1 h, and monitored by TLC (hexane:EtOAc, 9:1). The mixture is diluted with Et2O (5 mL), and a fine precipitate is filtered off. The filtrate is evaporated to an orange solid which is purified by preparative TLC (hexane:EtOAc, 9:1) to yield N-(7-tert-butyl-3,3-dimethyl-2,3-dihydrobenzo[b]furan-5-yl)acetamide as a white solid.
Reaction SMILES: [C:1]([C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[N:8]([S:12]([C:15]1[CH:20]=[CH:19][C:18]([CH3:21])=[CH:17][CH:16]=1)(=[O:14])=[O:13])[CH:7]=[C:6]2[C@H:22]1[CH2:24][C@H:23]1[CH:25]=O)#[N:2].[CH3:27][NH:28][CH3:29].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(O)C>[C:1]([C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[N:8]([S:12]([C:15]1[CH:20]=[CH:19][C:18]([CH3:21])=[CH:17][CH:16]=1)(=[O:14])=[O:13])[CH:7]=[C:6]2[C@H:22]1[CH2:24][C@H:23]1[CH2:25][N:28]([CH3:29])[CH3:27])#[N:2]
Reactant: CNC
Reactant: Cc1ccc(S(=O)(=O)n2cc([C@H]3C[C@H]3C=O)c3cc(C#N)ccc32)cc1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: CCO
Product: Cc1ccc(S(=O)(=O)n2cc([C@H]3C[C@H]3CN(C)C)c3cc(C#N)ccc32)cc1

Procedure:
A mixture of the crude cis-2-[5-Cyano-1-(p-toluenesulfonyl)indol-3-yl]cyclopropanecarboxaldehyde, dimethylamine (0.35 ml, 0.7 mmol, 2.0 M/THF), and anhydrous ethanol (10 ml) was heated with stirring until all solids were dissolved. The reaction vessel was removed from the heating source and sodium triacetoxyborohydride (300 mg, 1.41 mmol) was added. After stirring for 1 h, the solvent was evaporated. The residue was taken up in brine (10 ml) and aqueous 1N sodium hydroxide was added until solids disappeared. The aqueous layer was extracted with ethyl acetate ((4×10 ml), dried over anhydrous magnesium sulfate, and concentrated in vacuo to give the crude cis-2-[5-cyano-1-(p-toluenesulfonyl)indol-3-yl]-1-(N,N-dimethylaminomethyl)cyclopropane.
Reaction SMILES: [C:1]([N:5]1[C:9](=[O:10])[C:8](Cl)=[C:7]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[S:6]1(=[O:19])=[O:18])([CH3:4])([CH3:3])[CH3:2].C(C(C(C(O)=O)O)O)(O)=O.[CH3:30][C:31]1[CH:35]=[C:34]([CH3:36])[N:33]([CH2:37][CH2:38][CH2:39][NH2:40])[N:32]=1.C(N(CC)CC)C>CC#N>[C:1]([N:5]1[C:9](=[O:10])[C:8]([NH:40][CH2:39][CH2:38][CH2:37][N:33]2[C:34]([CH3:36])=[CH:35][C:31]([CH3:30])=[N:32]2)=[C:7]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[S:6]1(=[O:19])=[O:18])([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)N1C(=O)C(Cl)=C(c2ccccc2)S1(=O)=O
Reactant: Cc1cc(C)n(CCCN)n1
Agent: O=C(O)C(O)C(O)C(=O)O
Solvent: CCN(CC)CC
Solvent: CC#N
Product: Cc1cc(C)n(CCCNC2=C(c3ccccc3)S(=O)(=O)N(C(C)(C)C)C2=O)n1
Temperature: 120 °C
Yield: 93.6 %

Procedure:
2-tert-Butyl-4-chloro-5-phenylisothiazol-3(2H)-one 1,1-dioxide (150 mg, 0.5 mmol), 3-(3,5-dimethyl-pyrazol-1-yl)-propylamine tartrate (167 mg, 0.55 mmol) were mixed in MeCN (3 ml). Triethylamine (0.23 ml, 1.65 mmol) was added and the mixture was heated in a microwave reactor at 120° C. for 15 mins. The reaction mixture was evaporated to dryness and the residue was purified by column chromatography (ISOLUTE SI, 20 g/70 ml), eluting with DCM and then MeOH/DCM (1:99), to give the title compound (195 mg, 94%). 1H NMR (400 MHz, CDCl3): δ 1.70 (s, 9H), 1.72-1.79 (m, 2H), 2.05 (s, 3H), 2.18 (s, 3H), 2.81-2.86 (m 2H), 3.79 (t, 2H), 5.71 (bs, 2H), 7.37-7.46 (m, 5H); 13C NMR (100 MHz, CDCl3): δ 10.8, 13.4, 27.5, 29.2, 41.5, 45.4, 61.3, 105.1, 106.8, 125.0, 128.4, 129.4, 131.4, 135.0, 138.5, 147.7, 159.3; Mass Spectrum: M+H+ 417.
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[N:9]1[C:13]([C:14]2[N:23]=[C:22]3[N:16]([CH2:17][CH2:18][O:19][C:20]4[CH:27]=[C:26]([CH2:28][NH2:29])[CH:25]=[CH:24][C:21]=43)[CH:15]=2)=[N:12][C:11]([CH3:30])=[N:10]1.[O-:31][C:32]#[N:33].[K+]>C(O)(=O)C.O>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[N:9]1[C:13]([C:14]2[N:23]=[C:22]3[C:21]4[CH:24]=[CH:25][C:26]([CH2:28][NH:29][C:32]([NH2:33])=[O:31])=[CH:27][C:20]=4[O:19][CH2:18][CH2:17][N:16]3[CH:15]=2)=[N:12][C:11]([CH3:30])=[N:10]1
Reactant: Cc1nc(-c2cn3c(n2)-c2ccc(CN)cc2OCC3)n(-c2ccc(F)cc2F)n1
Reactant: N#C[O-]
Agent: [K+]
Solvent: CC(=O)O
Solvent: O
Product: Cc1nc(-c2cn3c(n2)-c2ccc(CNC(N)=O)cc2OCC3)n(-c2ccc(F)cc2F)n1

Procedure:
C-{2-[2-(2,4-Difluoro-phenyl)-5-methyl-2H-[1,2,4]triazol-3-yl]-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulen-8-yl}-methylamine in acetic acid and water was reacted with potassium cyanate in water to give 354. MS(ESI+) 452.1. 1H NMR (400 MHz, DMSO) δ 7.89 (s, 1H), 7.68 (td, J=8.7, 6.2 Hz, 1H), 7.62-7.54 (m, 2H), 7.32-7.25 (m, 1H), 6.87-6.80 (m, 2H), 6.44 (t, J=6.1 Hz, 1H), 5.57 (br, 2H), 4.49-4.38 (m, 4H), 4.12 (d, J=6.1 Hz, 2H), 2.35 (s, 3H)
Reaction SMILES: [CH:1]1(O)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([CH3:15])[CH:10]=1.P(OC1C=CC=CC=1)(OC1C=CC=CC=1)OC1C=CC=CC=1>O>[CH:1]1([NH:8][C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([CH3:15])[CH:10]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: Cc1cccc(N)c1
Reactant: OC1CCCCC1
Agent: c1ccc(OP(Oc2ccccc2)Oc2ccccc2)cc1
Solvent: O
Product: Cc1cccc(NC2CCCCC2)c1
Yield: 60 %

Procedure:
200 parts of cyclohexanol, 214 parts of m-toluidine and 10 parts of triphenyl phosphite are heated for 20 hours at 230° C in a stirred autoclave. The autoclave is then let down and the water of reaction formed, unconverted toluidine and excess alcohol are distilled off. 227 parts of N-cyclohexyl-m-toluidine, corresponding to a yield of 60% of theory, distil at a boiling point of 165° - 170° C/15 mm Hg.
Reaction SMILES: [NH2:1][C:2]1[CH:16]=[CH:15][C:14]([N+:17]([O-])=O)=[CH:13][C:3]=1[C:4]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[Cl:12])=[O:5].[Sn](Cl)Cl.[OH-].[Na+]>Cl>[NH2:1][C:2]1[CH:16]=[CH:15][C:14]([NH2:17])=[CH:13][C:3]=1[C:4]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[Cl:12])=[O:5]
Reactant: Nc1ccc([N+](=O)[O-])cc1C(=O)c1ccccc1Cl
Agent: Cl
Agent: Cl[Sn]Cl
Agent: [Na+]
Product: Nc1ccc(N)c(C(=O)c2ccccc2Cl)c1
Temperature: 25 °C
Reaction time: 36 h

Procedure:
100 g of 2-amino-2'-chloro-5-nitrobenzophenone are suspended in 865 ml of 25% hydrochloric acid and treated portionwise with a total of 269 g of tin (II) chloride. The mixture is stirred at room temperature for 36 hours, then diluted with 0.5 l of an ice/water mixture and adjusted to pH 10 with about 2.17 l of a 28% sodium hydroxide solution. The mixture is extracted with methylene chloride. After evaporation of the solvent, the residue is dissolved in 0.54 l of ether and crystallized at about -20°. There is obtained 2,5-diamino-2'-chlorobenzophenone of melting point 30°-40°.