Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1[NH:3][C:4]2[C:9]([CH:10]=1)=[C:8]([C:11]([F:14])([F:13])[F:12])[CH:7]=[CH:6][CH:5]=2.[BH3-]C#N.[Na+].[CH3:19][C:20](OC(C)=O)=[O:21]>CC(O)=O.CN(C1C=CN=CC=1)C.C(Cl)Cl>[C:20]([N:3]1[C:4]2[C:9](=[C:8]([C:11]([F:12])([F:14])[F:13])[CH:7]=[CH:6][CH:5]=2)[CH2:10][CH:2]1[CH3:1])(=[O:21])[CH3:19]
Reactant: Cc1cc2c(C(F)(F)F)cccc2[nH]1
Reactant: CC(=O)OC(C)=O
Agent: CN(C)c1ccncc1
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: ClCCl
Solvent: CC(=O)O
Product: CC(=O)N1c2cccc(C(F)(F)F)c2CC1C
Temperature: 0 °C
Reaction time: 14 h
Yield: 42.6 %

Procedure:
A mixture of 2-methyl-4-(trifluoromethyl)-1H-indole (Example 114D) (0.48 g, 2.41 mmol) was dissolved in HOAc (3.0 mL), cooled to 0° C. and NaBH3CN (0.454 g, 7.23 mmol) was added in one portion. After 5 min the mixture was removed from the cooling bath and stirred at rt for 14 h. The mixture cooled to 0° C. and the pH was adjusted to ca. 13 by addition of 1 N NaOH (20 mL) and further addition of solid NaOH pellets. The mixture was extracted with Et2O (×3), combined organics were washed (H2O, brine), dried over Na2SO4, filtered and concentrated in vacuo. The residue was dissolved in dry CH2Cl2 (10 mL) and treated with DMAP (0.884 g, 7.23 mmol). The mixture was cooled to 0° C. and Ac2O (0.455 mL, 4.81 mmol) was added dropwise via syringe. The mixture was stirred overnight, slowly warming to rt, diluted with CH2Cl2, washed (10% HCl, H2O, brine), dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by flash chromatography (EtOAc/hexanes), affording 0.25 g of the title compound as a pale yellow oil: MS (ES) m/z 244 (M+1).
Reaction SMILES: [K].[CH3:2][N:3]([CH3:32])[C:4]1[CH:31]=[CH:30][C:7]([CH:8]([C:18]2[CH:26]=[CH:25][C:24]([N:27]([CH3:29])[CH3:28])=[CH:23][C:19]=2[C:20]([OH:22])=[O:21])[C:9]2[CH:14]=[CH:13][C:12]([N:15]([CH3:17])[CH3:16])=[CH:11][CH:10]=2)=[CH:6][CH:5]=1>>[CH3:17][N:15]([CH3:16])[C:12]1[CH:11]=[CH:10][C:9]([C:8]2([C:7]3[CH:6]=[CH:5][C:4]([N:3]([CH3:2])[CH3:32])=[CH:31][CH:30]=3)[C:18]3[C:19](=[CH:23][C:24]([N:27]([CH3:29])[CH3:28])=[CH:25][CH:26]=3)[C:20](=[O:22])[O:21]2)=[CH:14][CH:13]=1
Reactant: CN(C)c1ccc(C(c2ccc(N(C)C)cc2)c2ccc(N(C)C)cc2C(=O)O)cc1
Agent: [K]
Product: CN(C)c1ccc(C2(c3ccc(N(C)C)cc3)OC(=O)c3cc(N(C)C)ccc32)cc1

Procedure:
Employing a procedure similar to that described in Example 1, part C above, the potassium salt solution of 2-[4,4'-bis(dimethylamino)benzhydryl]-5-dimethylaminobenzoic acid from A was oxidized to obtain 3,3-bis(4-dimethylaminophenyl)-6-dimethylaminophthalide (Formula I: R=CH3 ; X=H; Y=Z=4-(CH3)2NC6H4) a tan-colored solid.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-])=O)=[C:4]([O:11][CH2:12][CH2:13][O:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[N+:21]([O-])=O)[CH:3]=1.C(O)(=O)C>[Pd].O1CCOCC1>[NH2:21][C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=1[O:14][CH2:13][CH2:12][O:11][C:4]1[CH:3]=[C:2]([F:1])[CH:7]=[CH:6][C:5]=1[NH2:8]
Reactant: O=[N+]([O-])c1ccccc1OCCOc1cc(F)ccc1[N+](=O)[O-]
Agent: [Pd]
Solvent: C1COCCO1
Solvent: CC(=O)O
Product: Nc1ccccc1OCCOc1cc(F)ccc1N

Procedure:
9.48 g 4-fluoro-1-nitro-2-(2-(2-nitro-phenoxy)-ethoxy)-benzene and 1.5 g palladium on charcoal were suspended in 500 ml dioxane and 60 ml glacial acetic acid and hydrogenated at room temperature. After flashing three times with nitrogen the catalyst was filtered off under a nitrogen atmosphere and the remaining solution was evaporated and the product was dried under vacuum. Yield: 7.52 g.
Reaction SMILES: CS([C:4]1[N:9]=[CH:8][C:7]2=[CH:10][CH:11]=[C:12]([C:13]3[CH:14]=[N:15][C:16]([O:19][CH3:20])=[CH:17][CH:18]=3)[N:6]2[N:5]=1)=O.[O:21]=[S:22]1(=[O:36])[CH2:27][CH2:26][N:25]([CH2:28][C:29]2[CH:34]=[CH:33][C:32]([NH2:35])=[CH:31][CH:30]=2)[CH2:24][CH2:23]1>>[O:36]=[S:22]1(=[O:21])[CH2:23][CH2:24][N:25]([CH2:28][C:29]2[CH:34]=[CH:33][C:32]([NH:35][C:4]3[N:9]=[CH:8][C:7]4=[CH:10][CH:11]=[C:12]([C:13]5[CH:14]=[N:15][C:16]([O:19][CH3:20])=[CH:17][CH:18]=5)[N:6]4[N:5]=3)=[CH:31][CH:30]=2)[CH2:26][CH2:27]1
Reactant: Nc1ccc(CN2CCS(=O)(=O)CC2)cc1
Reactant: COc1ccc(-c2ccc3cnc(S(C)=O)nn23)cn1
Product: COc1ccc(-c2ccc3cnc(Nc4ccc(CN5CCS(=O)(=O)CC5)cc4)nn23)cn1

Procedure:
[4-(1,1-Dioxo-1$1(6)-thiomorpholin-4-ylmethyl)-phenyl]-[7-(6-methoxy-pyridin-3-yl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-amine was prepared from 2-methanesulfinyl-7-(6-methoxy-pyridin-3-yl)-pyrrolo[2,1-f][1,2,4]triazine and 4-(1,1-dioxo-1$1(6)-thiomorpholin-4-ylmethyl)-phenylamine in an analogous manner to Example 1049. Product isolated as a yellow foam (10 mg, 6%). LCMS (m/e) 465 (M+H); 1H-NMR (CDCl3, 400 MHz) δ 8.77 (d, 1H, J=2.1 Hz), 8.72 (s, 1H), 8.40 (dd, 1H, J=8.7 and 2.4 Hz), 7.58 (d, 2H, J=8.4 Hz), 7.26 (d, 2H, J=8.4 Hz), 6.94 (d, 1H, J=4.7 Hz), 6.92-6.84 (m, 2H), 6.82 (s, 1H), 4.04 (s, 3H), 3.62 (s, 2H), 3.10-3.03 (m, 4H), 3.03-2.96 (m, 4H).
Reaction SMILES: C([O:3][C:4](=O)[C:5](=[O:26])[N:6]1[CH2:11][CH2:10][CH:9]([C:12]2[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[C:14]([CH:20]=[C:21]3[CH2:25][CH2:24][CH2:23][CH2:22]3)[CH:13]=2)[CH2:8][CH2:7]1)C.[NH2:28][OH:29].Cl.[OH-].[K+].CO>CO>[C:21]1(=[CH:20][C:14]2[CH:13]=[C:12]([CH:9]3[CH2:10][CH2:11][N:6]([C:5](=[O:26])[C:4]([NH:28][OH:29])=[O:3])[CH2:7][CH2:8]3)[CH:17]=[CH:16][C:15]=2[O:18][CH3:19])[CH2:25][CH2:24][CH2:23][CH2:22]1
Reactant: CCOC(=O)C(=O)N1CCC(c2ccc(OC)c(C=C3CCCC3)c2)CC1
Reactant: NO
Agent: Cl
Agent: [K+]
Agent: [OH-]
Solvent: CO
Product: COc1ccc(C2CCN(C(=O)C(=O)NO)CC2)cc1C=C1CCCC1
Reaction time: 3 h

Procedure:
To a stirred solution of 2-[4-(3-cyclopentylidenemethyl-4-methoxy-phenyl)-piperidin-1-yl]-oxo-acetic acid ethyl ester (0.4 mmol, 0.150 g) in methanol (5 mL) was added hydroxylamine.HCl (1.6 mmol, 0.111 g), followed by potassium hydroxide/methanol solution (5 M solution; 0.4 mL) dropwise at room temperature. A white solid precipitated out of solution as this reaction stirred for 3 hours. The reaction went to completion as seen by TLC. The reaction mixture was diluted with H2O (100 mL), acidified with 1N HCl and extracted with EtOAc (3×100 mL). Each organic phase was washed with H2O (1×50 mL) and the combined organics were dried (Na2SO4) and concentrated in vacuo to a white solid. The solid was triturated in Et2O/hexane to afford pure white crystals which were dried overnight at 45° C. to give the title compound, mp 127°-128° C. (0.3 mmol, 0.017 g, 75%).
Reaction SMILES: C([O:4][C:5]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[C:8]([O:15][CH2:16][CH3:17])=[CH:7][C:6]=1[O:18][CH2:19][CH3:20])(=O)C.C(=O)([O-])[O-].[K+].[K+]>CO.O>[OH:4][C:5]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[C:8]([O:15][CH2:16][CH3:17])=[CH:7][C:6]=1[O:18][CH2:19][CH3:20]
Reactant: CCOc1cc(OCC)c2ccccc2c1OC(C)=O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Solvent: O
Product: CCOc1cc(OCC)c2ccccc2c1O

Procedure:
A solution of 1-acetyloxy-2,4-diethoxynaphthalene (2.74 g) in 100 ml of methanol and 10 ml of water was stirred with 2.5 g of potassium carbonate for 6 hours. The solvent was then removed under reduced pressure, and the residue partitioned between ethyl acetate and water. The ethyl acetate layer was dried over anhydrous sodium sulfate and evaporated to a solid, which was recrystallized from ethyl acetate/hexane to give 1-hydroxy-2,4-diethoxynaphthalene, m.p. 83°-84° C.
Reaction SMILES: Cl[C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][CH:5]=[C:4]([O:11][CH3:12])[N:3]=1.[CH3:13][N:14]([CH3:18])[CH2:15][CH2:16][NH2:17]>C(O)C>[CH3:12][O:11][C:4]1[N:3]=[C:2]([NH:17][CH2:16][CH2:15][N:14]([CH3:18])[CH3:13])[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][CH:5]=1
Reactant: COc1ccc([N+](=O)[O-])c(Cl)n1
Reactant: CN(C)CCN
Solvent: CCO
Product: COc1ccc([N+](=O)[O-])c(NCCN(C)C)n1
Temperature: 0 °C
Yield: 79.1 %

Procedure:
4 g (0.0212 mol) of the product 2-chloro-3-nitro-6-methoxypyridine, 40 ml of ethanol and 3.85 ml (0.0424 mol) of N,N-dimethylethylenediamine are placed in a fully equipped round-bottomed flask. The mixture is refluxed for 2 hours with stirring and is then poured onto an ice/water mixture with stirring. The precipitate formed is filtered off by suction and dried under vacuum to constant weight. 54.027 g of yellow powder are obtained, ie a yield of 79.1%.
Reaction SMILES: [CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.[S:11](=[O:15])(=[O:14])([OH:13])[OH:12]>>[C:9]1([S:11]([OH:14])(=[O:13])=[O:12])[C:10]2[C:5](=[CH:4][CH:3]=[CH:2][CH:1]=2)[CH:6]=[CH:7][CH:8]=1.[S:11](=[O:13])(=[O:12])([OH:15])[OH:14]
Reactant: c1ccc2ccccc2c1
Agent: O=S(=O)(O)O
Product: O=S(=O)(O)c1cccc2ccccc12
Temperature: 155 °C

Procedure:
128 g (1 m) of naphthalene and 160 g (1.6 m) of sulfuric acid 98% by weight were mixed together in a reaction flask. The resulting agitated reaction mixture was heated rapidly to 155° C. and was reacted for 3 hours at 155° C. to obtain a naphthalenesulfonic acid and sulfuric acid mixture. This mixture contained about 20% free sulfuric acid and solidified at about 80° C. The mixture was used either in solid or melted form.
Reaction SMILES: [OH:1][B:2]1[C:6]2[CH:7]=[CH:8][C:9]([O:11][C:12]3[CH:20]=[CH:19][C:15]([C:16]([OH:18])=O)=[CH:14][CH:13]=3)=[CH:10][C:5]=2[CH2:4][O:3]1.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.[CH2:42]([NH2:49])[C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1>CN(C1C=CN=CC=1)C.C(Cl)Cl.O>[CH2:42]([NH:49][C:16](=[O:18])[C:15]1[CH:14]=[CH:13][C:12]([O:11][C:9]2[CH:8]=[CH:7][C:6]3[B:2]([OH:1])[O:3][CH2:4][C:5]=3[CH:10]=2)=[CH:20][CH:19]=1)[C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1
Reactant: O=C(O)c1ccc(Oc2ccc3c(c2)COB3O)cc1
Reactant: NCc1ccccc1
Agent: CCN=C=NCCCN(C)C
Agent: CN(C)c1ccncc1
Agent: On1nnc2ccccc21
Solvent: O
Solvent: ClCCl
Product: O=C(NCc1ccccc1)c1ccc(Oc2ccc3c(c2)COB3O)cc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a 40 mL scintillation vial containing 4-(1-hydroxy-1,3-dihydro-benzo[c][1,2]oxaborol-5-yloxy)-benzoic acid (150 mg, 0.55 mmol, 1.0 eq.), EDCI (157.2 mg, 0.82 mmol, 1.5 eq.), HOBt (111.5 mg, 0.82 mmol, 1.5 eq.) and DMAP (12 mg, 0.1 mmol, 0.2 eq.) in DCM (10.0 mL) was added benzylamine (24 μL, 2.2 mmol, 4.0 eq.) drop wise. The mixture was stirred at room temperature overnight. The mixture was treated with H2O (10 mL) and the layers were separated. The aqueous was extracted with DCM (2×5 mL), combined organic phase was washed with brine (10 mL), dried over MgSO4, filtered and the filtrate was concentrated under reduced pressure. The residue was applied to silica chromatography eluting with MeOH/DCM (0:100 to 10:90) to give N-benzyl-4-(1-hydroxy-1,3-dihydro-benzo[c][1,2]oxaborol-5-yloxy)-benzamide as a white solid. LCMS (m/z) 360 (M+H); 1H NMR (DMSO-d6) δ: 9.01 (t, J=6.0 Hz, 1H), 7.91-8.00 (m, 2H), 7.76 (d, J=7.9 Hz, 1H), 7.29-7.36 (m, 5H), 7.21-7.27 (m, 1H), 7.08-7.13 (m, 2H), 7.02-7.07 (m, 2H), 4.95 (s, 2H), 4.48 (d, J=6.0 Hz, 2H).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][C:15]#[CH:16])[CH2:10][C@@H:9]1[C:17]([OH:19])=[O:18])=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:20](OC(N1CCN(C(C)C)C[C@@H]1C(O)=O)=O)(C)(C)C.C(Br)C#C>>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][C:15]([CH3:20])=[CH2:16])[CH2:10][C@@H:9]1[C:17]([OH:19])=[O:18])=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: C#CCN1CCN(C(=O)OC(C)(C)C)[C@@H](C(=O)O)C1
Reactant: CC(C)N1CCN(C(=O)OC(C)(C)C)[C@@H](C(=O)O)C1
Agent: C#CCBr
Product: C=C(C)CN1CCN(C(=O)OC(C)(C)C)[C@@H](C(=O)O)C1

Procedure:
(2R)-1-(tert-Butoxycarbonyl)-4-(prop-2-yn-1-yl)piperazine-2-carboxylic acid used in Route E1 was prepared using the procedure described for (2R)-1-(tert-butoxycarbonyl)-4-isopropylpiperazine-2-carboxylic acid above but using prop-2-ynyl bromide.
Reaction SMILES: [CH2:1]([O:5][CH2:6][CH2:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:16]=[CH:17][C:18]3[N:24](C(=O)C(F)(F)F)[CH2:23][CH2:22][C:21]([C:31]([NH:33][C:34]4[CH:39]=[CH:38][C:37]([CH:40]([OH:49])[C:41]5[CH:46]=[CH:45][CH:44]=[C:43]([CH3:47])[N+:42]=5[O-:48])=[CH:36][CH:35]=4)=[O:32])=[CH:20][C:19]=3[CH:50]=2)=[CH:11][CH:10]=1)[CH2:2][CH2:3][CH3:4].[BH4-].[Na+].O>C(O)C>[CH2:1]([O:5][CH2:6][CH2:7][O:8][C:9]1[CH:10]=[CH:11][C:12]([C:15]2[CH:16]=[CH:17][C:18]3[NH:24][CH2:23][CH2:22][C:21]([C:31]([NH:33][C:34]4[CH:35]=[CH:36][C:37]([CH:40]([OH:49])[C:41]5[CH:46]=[CH:45][CH:44]=[C:43]([CH3:47])[N+:42]=5[O-:48])=[CH:38][CH:39]=4)=[O:32])=[CH:20][C:19]=3[CH:50]=2)=[CH:13][CH:14]=1)[CH2:2][CH2:3][CH3:4]
Reactant: CCCCOCCOc1ccc(-c2ccc3c(c2)C=C(C(=O)Nc2ccc(C(O)c4cccc(C)[n+]4[O-])cc2)CCN3C(=O)C(F)(F)F)cc1
Agent: [BH4-]
Agent: [Na+]
Solvent: O
Solvent: CCO
Product: CCCCOCCOc1ccc(-c2ccc3c(c2)C=C(C(=O)Nc2ccc(C(O)c4cccc(C)[n+]4[O-])cc2)CCN3)cc1
Reaction time: 3 h
Yield: 60.9 %

Procedure:
To a solution of 7-[4-(2-butoxyethoxy)phenyl]-1-trifluoroacetyl-N-[4-[hydroxy(6-methyl-1-oxidopyridin-2-yl)methyl]phenyl]-2,3-dihydro-1H-1-benzazepine-4-carboxamide (230 mg) in ethanol (20 ml) was added sodium borohydride (63 mg) at room temperature and the mixture was stirred for 3 hours. To the reaction solution was added water and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over magnesium sulfate and concentrated under reduced pressure. The obtained residue was separated and purified by column chromatography (ethanol:ethyl acetate 1:4) and further recrystallized from ethyl acetate-diisopropylether to give 7-[4-(2-butoxyethoxy)phenyl]-N-[4-[hydroxy(6-methyl-1-oxidopyridin-2-yl)methyl]phenyl]-2,3-dihydro-1H-1-benzazepine-4-carboxamide (Compound 97) (120.5 mg) as yellow crystals.
Reaction SMILES: [Cl-].C[O:3][CH2:4][PH3+].C([Li])CCC.CC(C)([O-])C.[K+].[F:17][C:18]1[CH:19]=[C:20]([CH:26]2[CH2:31][CH2:30][C:29](=O)[CH2:28][CH2:27]2)[CH:21]=[CH:22][C:23]=1[C:24]#[N:25]>>[CH:4]([CH:29]1[CH2:28][CH2:27][CH:26]([C:20]2[CH:21]=[CH:22][C:23]([C:24]#[N:25])=[C:18]([F:17])[CH:19]=2)[CH2:31][CH2:30]1)=[O:3]
Reactant: COC[PH3+]
Reactant: N#Cc1ccc(C2CCC(=O)CC2)cc1F
Agent: CC(C)(C)[O-]
Agent: [Cl-]
Agent: [K+]
Product: N#Cc1ccc(C2CCC(C=O)CC2)cc1F

Procedure:
1,4-Cyclohexanedionemonoethyleneketal is reacted with a Grignard reagent prepared from 3-fluorobromobenzene (1), to obtain an alcohol form substance (2), followed by dehydrating it with an acid catalyst (such as p-toluenesulfonic acid, potassium hydrogen sulfate, hydrochloric acid, sulfuric acid, ion-exchange resin, etc.) to convert it into a cyclohexene derivative (3), thereafter subjecting the derivative to catalytic hydrogenation reaction in the presence of a catalyst such as Pd, Ni, Pt, etc., further deprotecting with an acidic aqueous solution (such as acetic acid, hydrochloric acid, formic acid, etc.), to obtain a cyclohexanone derivative (5), next reacting oxalyl chloride for acylation with the compound (5) in the presence of aluminum chloride, to obtain an acid chloride derivative (6), reacting aqueous ammonium with (6) to obtain an amide form substance (7), further reacting benzenesulfonyl chloride with (7) in pyridine, to obtain 4-(3-fluoro-4-cyanophenyl)cyclohexanone (8), reacting an ylide obtained by treating methoxymethylphosphonium chloride with a base (such as n-butyllithium, potassium-t-butoxide, etc.), with the cyclohexanone derivative (8) and further treating it in an acidic aqueous solution to obtain the objective 1-formyl-4-(3-fluoro-4-cyanophenyl) cyclohexane. 1-Formyl-4-(3,5-difluoro-4-cyanophenyl) cyclohexane, too, can be prepared in the same manner as the above, using 3,5-difluorobromobenzene as its raw material.
Reaction SMILES: [F:1][C:2]1[CH:28]=[CH:27][C:5]([CH2:6][NH:7][C:8](=O)[C:9]2[C:10](=[CH:22][CH:23]=[CH:24][CH:25]=2)[C:11]([NH:13][CH2:14][C:15]2[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=2)=O)=[CH:4][CH:3]=1.C1COCC1>CO>[C:9]1([CH2:8][NH:7][CH2:6][C:5]2[CH:27]=[CH:28][C:2]([F:1])=[CH:3][CH:4]=2)[CH:25]=[CH:24][CH:23]=[CH:22][C:10]=1[CH2:11][NH:13][CH2:14][C:15]1[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=1
Reactant: O=C(NCc1ccc(F)cc1)c1ccccc1C(=O)NCc1ccc(F)cc1
Solvent: C1CCOC1
Solvent: CO
Product: Fc1ccc(CNCc2ccccc2CNCc2ccc(F)cc2)cc1
Temperature: 0 °C
Yield: 81.9 %

Procedure:
To a 500 mL 3-neck round bottom flask fitted with condenser and nitrogen tube, was added N1,N2-bis(4-fluorobenzyl)phthalamide (2 g, 5.2 mmol, 1 eq) and THF (HPLC grade 100 mL). The clear solution was cooled to 0° C., before borondimethylsulphide (12 g, 15 mL, 164 mmol, 30 eq) was added slowly. The reaction mixture refluxed for 36 h, cooled to −10° C. to −15° C. and treated with methanol slowly through a dropping funnel until frothing stopped (50 mL). The reaction mixture concentrated to dryness and once again cooled to 0° C., before methanol (100 mL) was added slowly, The reaction mixture was refluxed for 40 h and concentrated under vacuum to dryness to give the crude product (1.5 g, 85%) as a solid, which was used without further purification. 1H NMR (400 MHz, DMSO-d6) δ 7.32-7.28 (m 6H), 7.22-7.19 (m, 2H), 7.10-7.05 (m, 4H), 3.72-3.64 (m, 8H). MS (ESI): 353.2 (M+H)+.
Reaction SMILES: [CH3:1][O-:2].[Na+].[NH2:4][C:5]1[N:10]=[C:9](C(Cl)(Cl)Cl)[N:8]=[C:7]([C:15]([F:18])([F:17])[F:16])[N:6]=1.O.Cl>CO>[NH2:4][C:5]1[N:10]=[C:9]([O:2][CH3:1])[N:8]=[C:7]([C:15]([F:18])([F:17])[F:16])[N:6]=1
Reactant: Nc1nc(C(F)(F)F)nc(C(Cl)(Cl)Cl)n1
Reactant: C[O-]
Agent: Cl
Agent: [Na+]
Solvent: CO
Solvent: O
Product: COc1nc(N)nc(C(F)(F)F)n1
Temperature: 5 °C
Reaction time: 1 h

Procedure:
1.8 g of a 30% by weight solution of sodium methanolate in methanol (corresponding to 0.01 mol of sodium methanolate) were added at 22° C. to a solution of 28.8 g (0.1 mol) of 2-amino-4-trichloromethyl-6-trifluoromethyl-1,3,5-triazine in 100 ml of methanol. The pale yellow solution was then refluxed for 30 minutes. The progress of the reaction was followed by thin-layer chromatography on silica gel (mobile phase: diethyl ether/hexane 1:1). After the reaction was complete, 20 ml of water were added, followed by 2 normal hydrochloric acid until the pH was 6-7. After this most of the methanol was removed at 40° C. under reduced pressure, adding 150 ml of water a little at a time so that the product did not agglomerate. To complete precipitation of the product, the resulting mixture was then stirred at 5° C. for 1 hour, after which the product was separated off, washed with a little water and dried at 40° C. under reduced pressure.
Reaction SMILES: [C@@H:1]1([NH2:7])[CH2:5][CH2:4][CH2:3][C@@H:2]1[NH2:6].C(N(CC)CC)C.ClC1C=C2C(=CC=1)N(C1C=CC=CC=1)C(S(Cl)(=O)=O)C2=S(=O)=O.[Cl:38][C:39]1[CH:40]=[C:41]2[C:45](=[CH:46][CH:47]=1)[N:44]([S:48]([C:51]1[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=1)(=[O:50])=[O:49])[C:43]([S:57](Cl)(=[O:59])=[O:58])=[CH:42]2>ClCCl.O>[Cl:38][C:39]1[CH:40]=[C:41]2[C:45](=[CH:46][CH:47]=1)[N:44]([S:48]([C:51]1[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=1)(=[O:49])=[O:50])[C:43]([S:57]([NH:6][C@@H:2]1[CH2:3][CH2:4][CH2:5][C@@H:1]1[NH2:7])(=[O:59])=[O:58])=[CH:42]2
Reactant: N[C@@H]1CCC[C@@H]1N
Reactant: O=S(=O)(Cl)c1cc2cc(Cl)ccc2n1S(=O)(=O)c1ccccc1
Agent: O=S(=O)=C1c2cc(Cl)ccc2N(c2ccccc2)C1S(=O)(=O)Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Solvent: O
Product: N[C@H]1CCC[C@H]1NS(=O)(=O)c1cc2cc(Cl)ccc2n1S(=O)(=O)c1ccccc1
Reaction time: 0.25 h
Yield: 407.2 %

Procedure:
cis-1,2-Cyclopentanediamine (WO98/30574) (348 mg) was dissolved in dichloromethane (10 ml), and to the solution triethylamine (1 ml) and 5-chloro-1-phenyl-sulfonylindole-2-sulfonyl chloride (390 mg) were added at 0° C. with stirring. After 15 minutes and 1 hour, 5-chloro-1-phenylsulfonylindole-2-sulfonyl chloride (156 mg) was additionally added. After stirring for 15 minutes, 5-chloro-1-phenylsulfonylindole-2-sulfonyl chloride (78 mg) was further added, and the mixture was stirred at room temperature for 2 hours. Water was added to the reaction mixture to separate an organic layer. The resultant organic layer was washed with a saturated solution of sodium hydrogencarbonate and dried over anhydrous sodium sulfate. The residue was purified by flash column chromatography on silica gel (chloroform:methanol=23:2) to obtain the title compound (739 mg) as a pale yellow solid.
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[NH:7][C:8]2[C:13]([CH:14]=1)=[CH:12][C:11]([C:15]([N:17]1[CH2:23][CH2:22][CH2:21][N:20]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:19][CH2:18]1)=[O:16])=[CH:10][CH:9]=2)=[O:5])[CH3:2].[CH:31](CS([O-])(=O)=O)([CH3:33])[CH3:32]>>[CH2:1]([O:3][C:4]([C:6]1[N:7]([CH:31]([CH3:33])[CH3:32])[C:8]2[C:13]([CH:14]=1)=[CH:12][C:11]([C:15]([N:17]1[CH2:23][CH2:22][CH2:21][N:20]([C:24]([O:26][C:27]([CH3:29])([CH3:28])[CH3:30])=[O:25])[CH2:19][CH2:18]1)=[O:16])=[CH:10][CH:9]=2)=[O:5])[CH3:2]
Reactant: CC(C)CS(=O)(=O)[O-]
Reactant: CCOC(=O)c1cc2cc(C(=O)N3CCCN(C(=O)OC(C)(C)C)CC3)ccc2[nH]1
Product: CCOC(=O)c1cc2cc(C(=O)N3CCCN(C(=O)OC(C)(C)C)CC3)ccc2n1C(C)C

Procedure:
The title compound was synthesized in analogy to example 239, Intermediate a), from 5-(4-tert-butoxycarbonyl-[1,4]diazepane-1-carbonyl)-1H-indole-2-carboxylic acid ethyl ester and isopropylmethanesulfonate, to afford the product as a yellow oil (62%).
Reaction SMILES: O[C:2]1[C:11]2[C:10]([C:12](OCC)=[O:13])=[CH:9][CH:8]=[CH:7][C:6]=2[NH:5][C:4](=[O:17])[C:3]=1[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.O.[NH2:25][NH2:26]>CO>[C:18]1([CH:3]2[C:2]3=[N:25][NH:26][C:12](=[O:13])[C:10]4[CH:9]=[CH:8][CH:7]=[C:6]([C:11]=43)[NH:5][C:4]2=[O:17])[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1
Reactant: NN
Reactant: CCOC(=O)c1cccc2[nH]c(=O)c(-c3ccccc3)c(O)c12
Solvent: CO
Solvent: O
Product: O=C1Nc2cccc3c(=O)[nH]nc(c23)C1c1ccccc1
Temperature: 110 °C
Reaction time: 2.5 h
Yield: 53 %

Procedure:
Ethyl 4-hydroxy-2-oxo-3-phenyl-1,2-dihydroquinoline-5-carboxylate (330 mg, 1.1 mmol) was added to hydrazine monohydrate (1 mL) and methanol (2 mL), the mixture was stirred at 110° C. for 2.5 h by microwave. Then the mixture was cooled to room temperature, the solvent was evaporated in vacuum. The residue was washed with methanol, and then purified by column chromatography (silica gel, dichloromethane/methanol=300:1 to 50:1) to obtain a pale white solid (148 mg, yield 53%). LC-MS (ESI) m/z: 278 (M+1)+. 1H-NMR (400 MHz, DMSO-d6) δ (ppm): 5.09 (s, 1H), 7.17-7.40 (m, 6H), 7.77-7.81 (m, 2H), 11.10 (s, 1H), 12.57 (s, 1H).
Reaction SMILES: [N:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)=[C:2]=[O:3].[NH2:10][CH2:11][CH2:12][CH2:13][N:14]1[CH2:19][CH2:18][CH:17]([C:20]2[CH:21]=[C:22]([NH:26][C:27](=[O:31])[CH:28]([CH3:30])[CH3:29])[CH:23]=[CH:24][CH:25]=2)[CH2:16][CH2:15]1>>[NH:1]([C:2]([NH:10][CH2:11][CH2:12][CH2:13][N:14]1[CH2:19][CH2:18][CH:17]([C:20]2[CH:21]=[C:22]([NH:26][C:27](=[O:31])[CH:28]([CH3:29])[CH3:30])[CH:23]=[CH:24][CH:25]=2)[CH2:16][CH2:15]1)=[O:3])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1
Reactant: O=C=Nc1ccccc1
Reactant: CC(C)C(=O)Nc1cccc(C2CCN(CCCN)CC2)c1
Product: CC(C)C(=O)Nc1cccc(C2CCN(CCCNC(=O)Nc3ccccc3)CC2)c1

Procedure:
Prepared by Procedure P and Scheme AB using isocyanatobenzene and N-{3-[1-(3-aminopropyl)-4-piperidinyl]phenyl}-2-methylpropanamide: ESMS m/e: 422.9 (M+H)+.
Reaction SMILES: [C:1]([C:5]1[CH:10]=[CH:9][C:8]([S:11]([N:14]2[CH2:23][CH2:22][C:21]3[C:16]([CH2:25][C:26]4[CH:31]=[CH:30][C:29](B5OC(C)(C)C(C)(C)O5)=[CH:28][CH:27]=4)([CH2:17][CH2:18][C:19](=[O:24])[CH:20]=3)[CH2:15]2)(=[O:13])=[O:12])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].CCN(CCN1[N:64]=[C:63]2[C:50]3C(SC4C2=CC=CC=4)=C(C)[CH:53]=[CH:54][C:49]1=3)CC>>[C:1]([C:5]1[CH:6]=[CH:7][C:8]([S:11]([N:14]2[CH2:23][CH2:22][C:21]3[C:16]([CH2:25][C:26]4[CH:27]=[CH:28][C:29]([N:64]5[CH2:53][CH2:54][CH2:49][CH2:50][CH2:63]5)=[CH:30][CH:31]=4)([CH2:17][CH2:18][C:19](=[O:24])[CH:20]=3)[CH2:15]2)(=[O:12])=[O:13])=[CH:9][CH:10]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)c1ccc(S(=O)(=O)N2CCC3=CC(=O)CCC3(Cc3ccc(B4OC(C)(C)C(C)(C)O4)cc3)C2)cc1
Reactant: CCN(CC)CCn1nc2c3c(c(C)ccc31)Sc1ccccc1-2
Product: CC(C)(C)c1ccc(S(=O)(=O)N2CCC3=CC(=O)CCC3(Cc3ccc(N4CCCCC4)cc3)C2)cc1

Procedure:
The following compounds were similarly prepared from 2-(4-t-Butylbenzenesulfonyl)-8a-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)benzyl]-1,3,4,7,8,8a-hexahydro-2H-isoquinolin-6-one (IA-5: Y=4-(B(OC(CH3)2C(CH3)2O)):