Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl.[C:2]([S:21][CH2:22][CH2:23][NH2:24])([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[CH3:25][O:26][C:27]1[CH:28]=[C:29]2[C:33](=[C:34]([NH:36][S:37]([C:40]3[S:41][CH:42]=[CH:43][CH:44]=3)(=[O:39])=[O:38])[CH:35]=1)[NH:32][C:31]([C:45](O)=[O:46])=[CH:30]2.N1(O)C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC>C(OCC)(=O)C.CN(C)C=O.C(N(CC)CC)C>[CH3:25][O:26][C:27]1[CH:28]=[C:29]2[C:33](=[C:34]([NH:36][S:37]([C:40]3[S:41][CH:42]=[CH:43][CH:44]=3)(=[O:39])=[O:38])[CH:35]=1)[NH:32][C:31]([C:45]([NH:24][CH2:23][CH2:22][S:21][C:2]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)([C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1)=[O:46])=[CH:30]2
Reactant: NCCSC(c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: COc1cc(NS(=O)(=O)c2cccs2)c2[nH]c(C(=O)O)cc2c1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: COc1cc(NS(=O)(=O)c2cccs2)c2[nH]c(C(=O)NCCSC(c3ccccc3)(c3ccccc3)c3ccccc3)cc2c1
Temperature: 25 °C
Reaction time: 15 h
Yield: 94.6 %

Procedure:
To a mixture of 2-(tritylthio)ethylamine hydrochloride (0.32 g), triethylamine (0.126 mL) and N,N-dimethylformamide (10 mL) were added 5-methoxy-7-[(2-thienylsulfonyl)amino]-1H-indole-2-carboxylic acid (265 mg), 1H-1,2,3-benzotriazol-1-ol (0.15 g) and N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride (188 mg) under ice-cooling, and the mixture was stirred at room temperature for 15 hr. The reaction mixture was diluted with ethyl acetate, washed with aqueous citric acid solution, aqueous sodium hydrogencarbonate solution and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The obtained oil was crystallized from dichloromethane-hexane to give the title compound (465 mg, yield 95%) as pale-yellow crystals. melting point 128-129° C.
Reaction SMILES: [N-:1]=[N+:2]=[N-:3].[Na+].[Cl-].[NH+:6]1C=CC=C[CH:7]=1.[CH3:12][O:13][C:14]1[CH:15]=[C:16]([CH:32]=[CH:33][C:34]=1[O:35][CH2:36][CH2:37][CH2:38][CH2:39][CH3:40])[CH:17]=[CH:18][C:19]([NH:21][C:22]1[C:27]2[O:28][CH2:29][CH2:30][O:31][C:26]=2[CH:25]=[CH:24][CH:23]=1)=[O:20]>CN(C)C=O.Cl>[CH3:12][O:13][C:14]1[CH:15]=[C:16]([CH:32]=[CH:33][C:34]=1[O:35][CH2:36][CH2:37][CH2:38][CH2:39][CH3:40])[CH:17]=[CH:18][C:19]([NH:21][C:22]1[C:27]2[O:28][CH:29]([C:7]3[NH:6][N:3]=[N:2][N:1]=3)[CH2:30][O:31][C:26]=2[CH:25]=[CH:24][CH:23]=1)=[O:20]
Reactant: [N-]=[N+]=[N-]
Reactant: CCCCCOc1ccc(C=CC(=O)Nc2cccc3c2OCCO3)cc1OC
Reactant: c1cc[nH+]cc1
Agent: Cl
Agent: [Cl-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCCCCOc1ccc(C=CC(=O)Nc2cccc3c2OC(c2nnn[nH]2)CO3)cc1OC
Temperature: 100 °C
Reaction time: 1.5 h

Procedure:
Sodium azide (490 mg) and pyridinium chloride (870 rag) were added to a solution of 8-(3-methoxy-4-pentyloxycinnamoyl) amino-1,4-benzodioxane (560 mg; synthesized in reference example 2) in dry dimethylformamide (3 ml). In an atmosphere of argon, the solution was stirred for 1.5 hrs at 100° C. The reaction solution cooled to room temperature was poured into IN hydrochloric acid, and the mixture was extracted with ethyl acetate. The extract was washed with water and a saturated aqueous solution of sodium chloride, dried, and then concentrated under reduced pressure. The residue was recrystallized from ethyl acetate to give the title compound (390 mg) having the following physical data:
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[C:12]([N:14]1[CH2:18][CH2:17][CH2:16][CH2:15]1)=[O:13])[N:8]=[CH:7][N:6]=[C:5]2[NH:19][CH:20]([C:26]1[N:30](C(OC(C)(C)C)=O)[C:29]2[CH:38]=[CH:39][C:40]([Cl:42])=[CH:41][C:28]=2[N:27]=1)[CH2:21][CH2:22][C:23](O)=[O:24].CN(C(ON1N=[N:58][C:53]2[CH:54]=[CH:55][CH:56]=[CH:57]C1=2)=[N+](C)C)C.[B-](F)(F)(F)F.FC(F)(F)C(O)=O.C(#[N:74])C.O1CCCC1>>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[C:12]([N:14]1[CH2:15][CH2:16][CH2:17][CH2:18]1)=[O:13])[N:8]=[CH:7][N:6]=[C:5]2[NH:19][CH:20]([C:26]1[NH:30][C:29]2[CH:38]=[CH:39][C:40]([Cl:42])=[CH:41][C:28]=2[N:27]=1)[CH2:21][CH2:22][C:23]([NH:74][CH:53]1[CH2:54][CH2:55][CH2:56][CH2:57][NH:58]1)=[O:24]
Reactant: CC(C)(C)OC(=O)n1c(C(CCC(=O)O)Nc2ncnc3cc(C(=O)N4CCCC4)c(Cl)cc23)nc2cc(Cl)ccc21
Reactant: CC#N
Reactant: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[B-](F)(F)F
Solvent: C1CCOC1
Solvent: O=C(O)C(F)(F)F
Product: O=C(CCC(Nc1ncnc2cc(C(=O)N3CCCC3)c(Cl)cc12)c1nc2cc(Cl)ccc2[nH]1)NC1CCCCN1

Procedure:
Prepared analogously to Example 61 from 6-chloro-4-[1-(1-tert.-butyloxycarbonyl-5-chloro-1H-benzimidazol-2-yl)-3-hydroxycarbonyl-propyl-amino]-7-(pyrrolidin-1-yl-carbonyl)-quinazoline and 2-amino-i-tert.-butyloxycarbonyl-piperidine with TBTU in acetonitrile/tetrahydrofuran and subsequent reaction with trifluoroacetic acid.
Reaction SMILES: C(OC(O[CH2:8][CH3:9])CBr)C.Br.C(=O)(O)[O-].[Na+].[NH2:16][C:17]1[N:18]=[N:19][C:20]([Cl:23])=[CH:21][CH:22]=1>C(O)(C)C>[Cl:23][C:20]1[CH:21]=[CH:22][C:17]2[N:18]([CH:8]=[CH:9][N:16]=2)[N:19]=1
Reactant: Nc1ccc(Cl)nn1
Reactant: CCOC(CBr)OCC
Agent: Br
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CC(C)O
Product: Clc1ccc2nccn2n1
Temperature: 25 °C
Reaction time: 0.05 h
Yield: 86 %

Procedure:
Bromoacetaldehyde diethylacetal (13.7 g, 69.5 mmol, 1.8 equiv) was added to hydrobromic acid (4.0 mL) and heated to reflux for 1.5 h. The reaction mixture was cooled to rt then poured into a reaction flask containing excess sodium bicarbonate in isopropanol. The solution was stirred for 3 min and then filtered. To the mother liquor was added 3-amino-6-chloropyridazine (5.0 g, 38.6 mmol, 1.0 equiv) and heated to reflux for 2 h. The reaction mixture was quenched with water and extracted with ethyl acetate. Purification using column chromatography gave 5.1 g of the brown solid, 86%: 1H NMR (400 MHz, CDCl3) δ 7.89 (s, 1H), 7.88 (d, J=9.3 Hz, 1H), 7.74 (s, 1H), 7.01 (d, J=9.3 Hz, 1H).
Reaction SMILES: [C:1](Cl)(=O)[C:2]([Cl:4])=[O:3].[N:7]1[CH:12]=[CH:11][CH:10]=[C:9](CC(O)=O)[CH:8]=1>C(Cl)Cl.CN(C=O)C>[N:7]1[CH:12]=[CH:11][CH:10]=[C:9]([CH2:1][C:2]([Cl:4])=[O:3])[CH:8]=1
Reactant: O=C(O)Cc1cccnc1
Reactant: O=C(Cl)C(=O)Cl
Solvent: ClCCl
Solvent: CN(C)C=O
Product: O=C(Cl)Cc1cccnc1
Temperature: 0 °C
Reaction time: 1 h

Procedure:
Oxalyl chloride (211 μl; 2.23 mmol; 1.2 eq.) was added to a suspension of 3-pyridineacetic acid (255 mg; 1.86 mmol; 1.0 eq.) in DCM/DMF (5 mL:3 μL) maintained at 0° C. under nitrogen atmosphere. The reaction mixture was then stirred at rt for 1 h. It was then concentrated under reduced pressure. The solid obtained was used as such in amidation reactions.
Reaction SMILES: FC(F)(F)S([O-])(=O)=O.C(OC([N:15]1[C@H:19]([CH2:20][C:21]2[S:25][C:24]3=[CH:26][N:27]([CH2:30][CH:31]4[CH2:33][CH2:32]4)[C:28]([CH3:29])=[N+:23]3[CH:22]=2)[CH2:18][C@H:17]([S:34][C:35]2[C@H:36]([CH3:52])[C@@H:37]3[C@@H:47]([C@H:48]([OH:50])[CH3:49])[C:46](=[O:51])[N:38]3[C:39]=2[C:40]([O:42]CC=C)=[O:41])[CH2:16]1)=O)C=C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N1CCOCC1>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.C1COCC1.C(O)C>[CH2:32]1[CH2:33][CH:31]1[CH2:30][N:27]1[CH:26]=[C:24]2[S:25][C:21]([CH2:20][C@H:19]3[NH:15][CH2:16][C@@H:17]([S:34][C:35]4[C@H:36]([CH3:52])[C@@H:37]5[C@@H:47]([C@H:48]([OH:50])[CH3:49])[C:46](=[O:51])[N:38]5[C:39]=4[C:40]([O-:42])=[O:41])[CH2:18]3)=[CH:22][N+:23]2=[C:28]1[CH3:29]
Reactant: C=CCOC(=O)C1=C(S[C@H]2C[C@@H](Cc3c[n+]4c(C)n(CC5CC5)cc4s3)N(C(=O)OCC=C)C2)[C@H](C)[C@@H]2[C@@H]([C@@H](C)O)C(=O)N12
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=S(=O)([O-])C(F)(F)F
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CCO
Solvent: C1CCOC1
Solvent: C1COCCN1
Product: Cc1n(CC2CC2)cc2sc(C[C@@H]3C[C@H](SC4=C(C(=O)[O-])N5C(=O)[C@H]([C@@H](C)O)[C@H]5[C@H]4C)CN3)c[n+]12
Temperature: 25 °C
Reaction time: 1 h
Yield: 6.4 %

Procedure:
Anhydrous THF (0.7 ml) and 0.7 ml of dry ethanol are added to 47.9 mg of allyl(1R,5S,6S)-2-[(3S,5S)-1-allyloxycarbonyl-5-[6-(2-cyclopropylmethyl)-5-methylimidazo[5,1-b]thiazolium-2-yl]methylpyrrolidin-3-yl]thio-6-((1R)-1-hydroxyethyl)-1-methylcarbapen-2-em-3-carboxylate trifluoromethanesulfonate. Triphenylphosphine (7.8 mg), 0.016 ml of morpholine, and 4.3 mg of tetrakis(triphenylphosphine)palladium(0) are successively added thereto, and the mixture is stirred in an argon atmosphere at room temperature for one hr. THF (10 ml) is added thereto, and the resultant precipitate is further washed twice with 3 ml of THF and dried in vacuo to give a yellow powder which is then purified by column chromatography on Cosmosil 40C18-PREP (water-methanol) to give 2.0 mg of the title compound as a slightly yellow powder.
Reaction SMILES: [N:1]1([CH2:7][CH2:8][CH2:9][O:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[CH:17]=[N:18][CH2:19][CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[BH4-].[Na+]>CO>[N:1]1([CH2:7][CH2:8][CH2:9][O:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[CH2:17][NH:18][CH2:19][CH2:20][C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)[CH2:2][CH2:3][O:4][CH2:5][CH2:6]1
Reactant: C(=NCCc1ccccc1)c1ccccc1OCCCN1CCOCC1
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Product: c1ccc(CCNCc2ccccc2OCCCN2CCOCC2)cc1
Yield: 74.9 %

Procedure:
N-[[2-[3-(4-Morpholinyl)propoxy]phenyl]methylene]-benzeneethanamine (17 g) is reduced with 5.4 g of sodium borohydride in 85 ml of methanol following the procedure described in Example 1B to yield 12.8 g of product as an oil, boiling point 219°-223° C. at 0.1-0.2 mm of Hg.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:25])[C:5]1[CH:10]=[CH:9][C:8]([NH2:11])=[C:7]([C:12](=[N:23][OH:24])[CH2:13][CH2:14][NH:15][C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH:6]=1)[CH3:2].CN(C1C=CC=CN=1)C.[C:35](OC(=O)C)(=[O:37])[CH3:36].O>ClCCl.CCOCC>[CH2:1]([O:3][C:4](=[O:25])[C:5]1[CH:10]=[CH:9][C:8]([NH2:11])=[C:7]([C:12](=[N:23][O:24][C:35](=[O:37])[CH3:36])[CH2:13][CH2:14][NH:15][C:16]([O:18][C:19]([CH3:20])([CH3:21])[CH3:22])=[O:17])[CH:6]=1)[CH3:2]
Reactant: CCOC(=O)c1ccc(N)c(C(CCNC(=O)OC(C)(C)C)=NO)c1
Reactant: CC(=O)OC(C)=O
Agent: CN(C)c1ccccn1
Solvent: ClCCl
Solvent: CCOCC
Solvent: O
Product: CCOC(=O)c1ccc(N)c(C(CCNC(=O)OC(C)(C)C)=NOC(C)=O)c1
Yield: 79.9 %

Procedure:
To a stirred solution of ethyl-4-amino-3-[3'-(N-tert-butyloxycarbonylamino)-1'-hydroxyiminopropyl]benzoate (4.8 g, 14 mmol) and dimethylamino pyridine (1.67 g, 14 mmol) in dichloromethane (200 ml) was added acetic anhydride (1.3 ml, 14 mmol), under an atmosphere of nitrogen. After 2 hours the solution was poured into water (200 ml) and partitioned. The organic layer was separated, washed once more with water (200 ml), then the combined organic phases dried (MgSO4). The solvent was removed in vacuo, to afford an oily solid. Ether (200 ml) was added, and the mixture evaporated in vacuo once more to give a white solid. The solid was taken up in more ether (100 ml) and filtered off, to afford the title compound (4.4 g, 82%) as a white solid. m.p. 130°-135° C. NMR δ (250 MHz, CDCl3) 1.40 (12H, m), 2.27 (3H, s), 3.18 (2 H, t, J=7 Hz), 3.43 (2H, m), 4.33 (2H, q, J=7 Hz), 4.70 (1H, br s), 6.69 (1H, d, J=9 Hz), 7.82 (1H, dd, J=9 and 2 Hz), 8.17 (1H, br s).
Reaction SMILES: [C:1]([NH:8][C@H:9]([C:19]([OH:21])=O)[CH2:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]#[N:18])=[CH:13][CH:12]=1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].FC1C(O)=C(F)C(F)=C(F)C=1F.[CH3:34][N:35]1CCOCC1.C(O)C>C(Cl)Cl>[CH3:34][NH:35][C:19](=[O:21])[C@H:9]([CH2:10][C:11]1[CH:12]=[CH:13][C:14]([C:17]#[N:18])=[CH:15][CH:16]=1)[NH:8][C:1]([O:3][C:4]([CH3:5])([CH3:6])[CH3:7])=[O:2]
Reactant: CC(C)(C)OC(=O)N[C@@H](Cc1ccc(C#N)cc1)C(=O)O
Reactant: CN1CCOCC1
Agent: Oc1c(F)c(F)c(F)c(F)c1F
Solvent: CCO
Solvent: ClCCl
Product: CNC(=O)[C@H](Cc1ccc(C#N)cc1)NC(=O)OC(C)(C)C
Reaction time: 3 h
Yield: 91.9 %

Procedure:
A solution of N-Boc-4-cyanophenylalanine (1.92 g, 6.6 mmol) and pentafluorophenol (2.43 g, 13.2 mmol) in CH2Cl2 (30 ml) at 0° C. was treated with 4-methylmorpholine (0.74 g, 7.3 mmol). After stirring the reaction mixture for 3 hours, 8M methylazine in ethanol (15 ml, 19.8 mmol) was added and the reaction mixture left to stir at room temperature for 16 hours. The solvent was removed under pressure, the residue dissolved in CH2Cl2 (50 ml) and washed with saturated sodium bicarbonate (2×50 ml) , 1M citric acid (2×50 ml) and brine (50 ml). The CH2Cl2 layer was dried over MgSO4 and the solvent removed under pressure to yield the title compound as a white solid (1.84 g, 92%).
Reaction SMILES: [CH2:1]([NH:3][C:4](=[O:15])[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[Si:11]([CH3:14])([CH3:13])[CH3:12])[CH3:2].[N+:16]([O-])([OH:18])=[O:17].S(=O)(=O)(O)O>ClCl>[CH2:1]([NH:3][C:4](=[O:15])[C:5]1[CH:10]=[C:9]([N+:16]([O-:18])=[O:17])[CH:8]=[CH:7][C:6]=1[Si:11]([CH3:14])([CH3:13])[CH3:12])[CH3:2]
Reactant: CCNC(=O)c1ccccc1[Si](C)(C)C
Reactant: O=[N+]([O-])O
Agent: ClCl
Agent: O=S(=O)(O)O
Product: CCNC(=O)c1cc([N+](=O)[O-])ccc1[Si](C)(C)C
Temperature: 0 °C
Reaction time: 0.17 h
Yield: 60 %

Procedure:
To a solution of the amide of example 49 (1.10 g, 5 mmol) in CH2 Cl2 (50 mL) at 0° C. was added dropwise over 2 min, a cold mixture of 70% nitric acid (0.95 mL, 15 mmol) and concentrated sulfuric acid (5 mL) dropwise. The mixture was stirred at 0° C. for 10 min and was poured onto ice. The mixture was extracted with ethyl acetate, the combined organic layers washed with brine, sat NaHCO3, brine, dried (MgSO4) and concentrated to a solid (2.68 g, 101%) consisting of a 2:1 ratio of 5-nitro and 3-nitro isomers. The title compound was obtained by RC (ethyl acetate/hexanes) in 60% yield as a white solid. m.p. 100°-102° C.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.ClCCCl.[N+:12]([O-:15])([OH:14])=[O:13]>O>[N+:12]([C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1[Cl:1])([O-:14])=[O:13].[N+:12]([C:5]1[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=1)([O-:15])=[O:13]
Reactant: Clc1ccccc1
Reactant: O=[N+]([O-])O
Solvent: O
Solvent: ClCCCl
Product: O=[N+]([O-])c1ccc(Cl)cc1
Product: O=[N+]([O-])c1ccccc1Cl
Temperature: 110 °C
Reaction time: 8 h
Yield: 38.2 %
Yield: 61.8 %

Procedure:
A 100 mL reaction flask fitted with reverse dean-stark apparatus was charged with 11.250 g chlorobenzene (0.1 mol), 48 mL 1,2 dichloro ethane and 2.250 g of catalyst as prepared example 5. The flask was flushed with nitrogen. The reaction mixture was refluxed at 110° C. for 1 h followed by the dropwise addition of 8.6 mL (0.133 mol) 70% HNO3. The water formed during the reaction was removed using fitted with reverse dean-stark apparatus. The reaction was carried out for 8 h. The reaction was monitored by GC analysis. In this reaction 55.2% conversion of chlorobenzene was obtained with 61.8% of 2-nitro chlorobenzene and 38.2% of 4-nitro chlorobenzene.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[Cl:11])[NH:7][C:6]([Si:12]([CH2:17][CH3:18])([CH2:15][CH3:16])[CH2:13][CH3:14])=[C:5]2[CH2:19][CH2:20]O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Br:41]C(Br)(Br)Br>C1COCC1>[Br:41][CH2:20][CH2:19][C:5]1[C:4]2[C:8](=[CH:9][C:10]([Cl:11])=[C:2]([Cl:1])[CH:3]=2)[NH:7][C:6]=1[Si:12]([CH2:17][CH3:18])([CH2:15][CH3:16])[CH2:13][CH3:14]
Reactant: CC[Si](CC)(CC)c1[nH]c2cc(Cl)c(Cl)cc2c1CCO
Reactant: BrC(Br)(Br)Br
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: CC[Si](CC)(CC)c1[nH]c2cc(Cl)c(Cl)cc2c1CCBr
Reaction time: 0.5 h
Yield: 27.2 %

Procedure:
A solution of 2-(5,6-dichloro-2-(triethylsilyl)-1H-indol-3-yl)ethanol (1.7 g; 4.94 mmol) in THF (6 mL) was added to a solution of triphenylphosphine (2.59 g; 9.87 mmol) and perbromomethane (3.27 g; 9.87 mmol) in THF (40 mL) pre-stirred for 30 minutes. The resulting mixture was stirred at room temperature for 18 hours. The reaction mixture was then filtered and concentrated under reduced pressure. The crude residue was purified by flash chromatography on silica gel (eluent 2 to 20% ethyl acetate in heptane) to afford 0.548 g (27%) of the title compound as a brown oil.
Reaction SMILES: [CH2:1]=[CH:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[CH:9]([Si:12]([C:19]#[C:20][SiH:21](C)[CH:22]=CC1C=CC=CC=1)([CH:16]([CH3:18])[CH3:17])[CH:13]([CH3:15])[CH3:14])([CH3:11])[CH3:10].[C:31]1(C)[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1>>[CH:16]([Si:12]([C:19]#[C:20][Si:21]([CH3:22])([C:31]1[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=1)/[CH:1]=[CH:2]/[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1)([CH:13]([CH3:15])[CH3:14])[CH:9]([CH3:10])[CH3:11])([CH3:17])[CH3:18]
Reactant: C=Cc1ccccc1
Reactant: Cc1ccccc1
Reactant: CC(C)[Si](C#C[SiH](C)C=Cc1ccccc1)(C(C)C)C(C)C
Product: CC(C)[Si](C#C[Si](C)(/C=C/c1ccccc1)c1ccccc1)(C(C)C)C(C)C
Temperature: 90 °C

Procedure:
In the same reactor, a 0.01 g carbonylchlorohydridebis(tricyclohexylphosphine)ruthenium(II) was added and then, in the following order: 1.84 mL toluene and 0.43 g styrene, were added to a mixture of raw [(tri(isopropyl)silyl)ethynyl]methylphenylvinylsilane and the inactive Step-1 catalyst at a room temperature and under inert gas conditions. The reaction mixture was heated at 90° C. for twenty four hours. Product was separated under the purification conditions of Example I. The product, [(tri(isopropyl)silyl)ethynyl]-methylphenyl-[(E)-styryl]silane, was obtained with a total yield of 85% pure product, in the form of an oily liquid, light yellow in color.
Reaction SMILES: [C:1]1([S:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][O:14][C:15]2[CH:16]=[C:17]3[C:22](=[CH:23][CH:24]=2)[NH:21][C:20](=[O:25])[CH2:19][CH2:18]3)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[OH:26]O>>[C:1]1([S:7]([CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][O:14][C:15]2[CH:16]=[C:17]3[C:22](=[CH:23][CH:24]=2)[NH:21][C:20](=[O:25])[CH2:19][CH2:18]3)=[O:26])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: OO
Reactant: O=C1CCc2cc(OCCCCCCSc3ccccc3)ccc2N1
Product: O=C1CCc2cc(OCCCCCCS(=O)c3ccccc3)ccc2N1

Procedure:
Prepared analogous to Example 2 from 6-(6-phenylmercapto-hexoxy)-3,4-dihydro-carbostyril and hydrogen peroxide.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[N:6][C:5]([N:8]=[CH:9]N(C)C)=[CH:4][CH:3]=1.Br[CH2:14][C:15]([C:17]1[CH:18]=[C:19]2[C:24](=[CH:25][CH:26]=1)[N:23]=[CH:22][CH:21]=[CH:20]2)=[O:16].C(N(CC)CC)C>O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:14]([C:15]([C:17]3[CH:18]=[C:19]4[C:24](=[CH:25][CH:26]=3)[N:23]=[CH:22][CH:21]=[CH:20]4)=[O:16])=[CH:9][N:8]=2)[N:7]=1
Reactant: O=C(CBr)c1ccc2ncccc2c1
Reactant: CN(C)C=Nc1ccc(Cl)nn1
Solvent: O
Solvent: CCN(CC)CC
Product: O=C(c1ccc2ncccc2c1)c1cnc2ccc(Cl)nn12

Procedure:
A mixture of N′-(6-chloro-pyridazin-3-yl)-N,N-dimethyl-formamidine (Stage 1.6, 2 g, 10.8 mmol), 2-bromo-1-quinolin-6-yl-ethanone (Stage 1.3, 3.36 g, 10.8 mmol) and triethylamine (1.1 g, 10.8 mmol) was stirred under reflux for 90 min. The reaction was allowed to cool and water (100 mL) was then added. The resulting red precipitate was filtered off to afford the title compound as a red solid (tR 1.2 min(conditions 1), MH+=309).
Reaction SMILES: [C:1]1([CH:7](Br)[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[OH:15][CH:16]1[CH2:21][CH2:20][N:19]([CH2:22][CH2:23][CH2:24][O:25][C:26]2[CH:31]=[CH:30][CH:29]=[C:28]([CH3:32])[C:27]=2[N+:33]([O-:35])=[O:34])[CH2:18][CH2:17]1.OC1CCN(CCCOC2C=CC=CC=2[N+]([O-])=O)CC1>>[C:1]1([CH:7]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[O:15][CH:16]2[CH2:17][CH2:18][N:19]([CH2:22][CH2:23][CH2:24][O:25][C:26]3[CH:31]=[CH:30][CH:29]=[C:28]([CH3:32])[C:27]=3[N+:33]([O-:35])=[O:34])[CH2:20][CH2:21]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: Cc1cccc(OCCCN2CCC(O)CC2)c1[N+](=O)[O-]
Reactant: BrC(c1ccccc1)c1ccccc1
Agent: O=[N+]([O-])c1ccccc1OCCCN1CCC(O)CC1
Product: Cc1cccc(OCCCN2CCC(OC(c3ccccc3)c3ccccc3)CC2)c1[N+](=O)[O-]

Procedure:
The procedure of Example 1 (a) was repeated except for using diphenylmethyl bromide and 4-hydroxy-1-[3-(3-methyl-2-nitrophenoxy)propyl]piperidine instead of diphenylmethyl bromide and 4-hydroxy-1-[3-(2-nitrophenoxy)propyl]piperidine to give oily 4-diphenylmethoxy-1-[3-(3-methyl-2-nitrophenoxy)propyl]piperidine.
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[CH:9][C:8]([S:11](Cl)(=[O:13])=[O:12])=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[NH:15]1[CH2:20][CH2:19][CH:18]([CH2:21][OH:22])[CH2:17][CH2:16]1>C(Cl)Cl>[Cl:1][C:2]1[CH:10]=[CH:9][C:8]([S:11]([N:15]2[CH2:20][CH2:19][CH:18]([CH2:21][OH:22])[CH2:17][CH2:16]2)(=[O:13])=[O:12])=[CH:7][C:3]=1[C:4]([OH:6])=[O:5]
Reactant: O=C(O)c1cc(S(=O)(=O)Cl)ccc1Cl
Reactant: OCC1CCNCC1
Solvent: ClCCl
Product: O=C(O)c1cc(S(=O)(=O)N2CCC(CO)CC2)ccc1Cl
Temperature: 25 °C
Reaction time: 8 h

Procedure:
2-Chloro-5-chlorosulfonylbenzoic acid (5.0 g.) is added to a solution of 4-piperidyl carbinol (6.9 g.) in 40 ml. of methylene chloride. The solution is refluxed for 2 hours, cooled to room temperature and stirred overnight. The solution is evaporated to dryness, the gummy residue dissolved in 1 N sodium hydroxide, and the alkaline solution extracted twice with ether. The aqueous solution is acidified with concentrated hydrochloric acid, and the precipitate recovered by filtration. Recrystallization from ethyl acetate yields crystals, m.p. 185°-187° C.
Reaction SMILES: [F:1][C:2]1[C:3]([CH3:22])=[C:4]2[C:9](=[C:10]([F:13])[C:11]=1F)[N:8]([CH:14]=[CH2:15])[CH:7]=[C:6]([C:16]([O:18]CC)=[O:17])[C:5]2=[O:21].[NH:23]1[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]1.C(#N)C>>[F:1][C:2]1[C:3]([CH3:22])=[C:4]2[C:9](=[C:10]([F:13])[C:11]=1[N:23]1[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]1)[N:8]([CH:14]=[CH2:15])[CH:7]=[C:6]([C:16]([OH:18])=[O:17])[C:5]2=[O:21]
Reactant: C=Cn1cc(C(=O)OCC)c(=O)c2c(C)c(F)c(F)c(F)c21
Reactant: C1CNCCN1
Solvent: CC#N
Product: C=Cn1cc(C(=O)O)c(=O)c2c(C)c(F)c(N3CCNCC3)c(F)c21
Temperature: 80 °C
Yield: 50.9 %

Procedure:
A solution of 0.69 g (1.80 mmol) of ethyl 6,7,8-trifluoro-1,4-dihydro-5-methyl-4-oxo-1-vinyl-3-quinolinecarboxylate, 0.62 g (7.2 mmol) of anhydrous piperazine, and 20 mmol of acetonitrile was refluxed for 18 hours, cooled, and concentrated. The residue was suspended in 25 mL of 1N sodium hydroxide and heated at 80° C. for 90 minutes. The clear yellow solution was cooled to room temperature, filtered, and neutralized (pH 6.8) with 6N hydrochloric acid. The solids were filtered, washed with water and ether, and dried to give 0.32 g of the title compound, mp 222°-225° C.
Reaction SMILES: Br[C:2]1[C:7](=[O:8])[CH:6]=[CH:5][N:4]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([C:15]([F:18])([F:17])[F:16])[CH:10]=2)[N:3]=1.[C:19]1([C:25]2[C:29](B(O)O)=[CH:28][N:27]([C:33]([C:46]3[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=3)([C:40]3[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=3)[C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)[N:26]=2)[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.C([O-])([O-])=O.[Na+].[Na+].COCCOC>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.O>[C:19]1([C:25]2[C:29]([C:2]3[C:7](=[O:8])[CH:6]=[CH:5][N:4]([C:9]4[CH:14]=[CH:13][CH:12]=[C:11]([C:15]([F:18])([F:17])[F:16])[CH:10]=4)[N:3]=3)=[CH:28][N:27]([C:33]([C:46]3[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=3)([C:40]3[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=3)[C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)[N:26]=2)[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1
Reactant: O=c1ccn(-c2cccc(C(F)(F)F)c2)nc1Br
Reactant: OB(O)c1cn(C(c2ccccc2)(c2ccccc2)c2ccccc2)nc1-c1ccccc1
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: COCCOC
Solvent: O
Product: O=c1ccn(-c2cccc(C(F)(F)F)c2)nc1-c1cn(C(c2ccccc2)(c2ccccc2)c2ccccc2)nc1-c1ccccc1
Temperature: 25 °C
Yield: 66.9 %

Procedure:
A mixture of 3-bromo-1-[3-(trifluoromethyl)phenyl]pyridazin-4(1H)-one (319 mg, 1.0 mmol), (3-phenyl-1-trityl-1H-pyrazol-4-yl)boronic acid (645 mg, 1.5 mmol), Pd(PPh3)4 (58 mg, 0.05 mmol), Na2CO3 (318 mg, 3.0 mmol), DME (7.5 mL), and H2O (1.5 mL) was refluxed overnight under Ar atmosphere. After cooling to room temperature, the reaction mixture was poured into water and extracted with AcOEt. The extract was washed with brine, dried over MgSO4, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography eluting with hexane/AcOEt (1/1) and crystallized from MeOH to give the title compound (418 mg, 67% yield) as a white solid: