Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([O:8][Si](C(C)(C)C)(C)C)=[CH:4][CH:3]=1.C([Si:19]1([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34]C=2)[CH2:24][CH2:23][CH:22]([CH:25]2[CH2:30][CH2:29][C:28](=O)[CH2:27][CH2:26]2)[CH2:21][CH2:20]1)CC.Br[CH2:39][CH2:40][C:41]([F:44])([F:43])[F:42]>>[CH2:32]([Si@H:19]1[CH2:20][CH2:21][C@H:22]([C@H:25]2[CH2:26][CH2:27][C@H:28]([C:2]3[CH:3]=[CH:4][C:5]([O:8][CH2:39][CH2:40][C:41]([F:44])([F:43])[F:42])=[CH:6][CH:7]=3)[CH2:29][CH2:30]2)[CH2:23][CH2:24]1)[CH2:37][CH2:36][CH2:35][CH3:34]
Reactant: CCC[Si]1(c2ccccc2)CCC(C2CCC(=O)CC2)CC1
Reactant: FC(F)(F)CCBr
Reactant: CC(C)(C)[Si](C)(C)Oc1ccc(Br)cc1
Product: CCCCC[Si@H]1CC[C@H]([C@H]2CC[C@H](c3ccc(OCCC(F)(F)F)cc3)CC2)CC1

Procedure:
The general procedure of Example 1 was repeated using 1-bromo-4-(t-butyldimethylsiloxy)benzene, 4-(4-n-propyl-4-phenyl-4-silacyclohexyl)cyclohexanone and 1-bromo-3,3,3-trifluoro-n-propane, thereby obtaining the intended compound.
Reaction SMILES: [C:1]1([CH:7]2[N:11]([C:12]([CH3:15])([CH3:14])[CH3:13])[CH2:10][CH:9]([CH2:16][OH:17])[O:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:18]1([CH3:28])[CH:23]=[CH:22][C:21]([S:24](Cl)(=[O:26])=[O:25])=[CH:20][CH:19]=1.O>C(N(CC)CC)C>[C:1]1([CH:7]2[N:11]([C:12]([CH3:13])([CH3:14])[CH3:15])[CH2:10][CH:9]([CH2:16][O:17][S:24]([C:21]3[CH:22]=[CH:23][C:18]([CH3:28])=[CH:19][CH:20]=3)(=[O:26])=[O:25])[O:8]2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: CC(C)(C)N1CC(CO)OC1c1ccccc1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Solvent: CCN(CC)CC
Solvent: O
Product: Cc1ccc(S(=O)(=O)OCC2CN(C(C)(C)C)C(c3ccccc3)O2)cc1

Procedure:
To a solution of dl-2-phenyl-3-t-butyl-5-hydroxymethyloxazolidine (12.05 g.) in triethylamine (120 ml.) 13 is added p-toluenesulfonylchloride (14.5 g.). After 6 days at room temperature the mixture is added to water (500 ml.) and extracted with ether (2×200 ml.). The ether solution is washed with water, dried with anhydrous magnesium sulfate and evaporated to dryness. The residue is recrystallized from hexane to afford 2-phenyl-3-t-butyl-5-p-toluenesulfonyloxymethyloxazolidine.
Reaction SMILES: [Cl:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH2:15][CH2:16][CH2:17][N:18]3[CH2:22][CH2:21][CH2:20][CH2:19]3)=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][N:3]=1.[NH2:23][C:24]1[CH:25]=[C:26]2[C:30](=[CH:31][CH:32]=1)[NH:29][C:28]([CH3:33])=[C:27]2[CH3:34]>>[ClH:1].[CH3:33][C:28]1[NH:29][C:30]2[C:26]([C:27]=1[CH3:34])=[CH:25][C:24]([NH:23][C:2]1[C:11]3[C:6](=[CH:7][C:8]([O:14][CH2:15][CH2:16][CH2:17][N:18]4[CH2:22][CH2:21][CH2:20][CH2:19]4)=[C:9]([O:12][CH3:13])[CH:10]=3)[N:5]=[CH:4][N:3]=1)=[CH:32][CH:31]=2
Reactant: COc1cc2c(Cl)ncnc2cc1OCCCN1CCCC1
Reactant: Cc1[nH]c2ccc(N)cc2c1C
Product: COc1cc2c(Nc3ccc4[nH]c(C)c(C)c4c3)ncnc2cc1OCCCN1CCCC1
Product: Cl
Yield: 76.3 %

Procedure:
Using an analogous procedure to that described in Example 37, 4-chloro-6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinazoline (100 mg, 0.31 mmol), (prepared as described for the starting material in Example 9), was reacted with 5-amino-2,3-dimethylindole (55 mg, 0.34 mmol) to give 4-(2,3-dimethylindol-5-ylamino)-6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinazoline hydrochloride (114 mg, 72%).
Reaction SMILES: Cl.C[O:3][C:4](=[O:16])[C@H:5]([NH2:15])[CH2:6][C:7]1[CH:12]=[CH:11][C:10]([Cl:13])=[CH:9][C:8]=1[Cl:14].[Cl:17][C:18]1[CH:26]=[CH:25][C:21]([C:22](O)=[O:23])=[C:20]([NH:27][S:28]([C:31]2[C:36]([F:37])=[CH:35][CH:34]=[CH:33][C:32]=2[F:38])(=[O:30])=[O:29])[CH:19]=1>>[Cl:17][C:18]1[CH:26]=[CH:25][C:21]([C:22]([NH:15][CH:5]([CH2:6][C:7]2[CH:12]=[CH:11][C:10]([Cl:13])=[CH:9][C:8]=2[Cl:14])[C:4]([OH:3])=[O:16])=[O:23])=[C:20]([NH:27][S:28]([C:31]2[C:32]([F:38])=[CH:33][CH:34]=[CH:35][C:36]=2[F:37])(=[O:30])=[O:29])[CH:19]=1
Reactant: O=C(O)c1ccc(Cl)cc1NS(=O)(=O)c1c(F)cccc1F
Reactant: COC(=O)[C@H](N)Cc1ccc(Cl)cc1Cl
Agent: Cl
Product: O=C(NC(Cc1ccc(Cl)cc1Cl)C(=O)O)c1ccc(Cl)cc1NS(=O)(=O)c1c(F)cccc1F

Procedure:
(R)-2-Amino-3-(2,4-dichloro-phenyl)-propionic acid was treated as in EXAMPLE 2, Part A, to produce (R)-2-amino-3-(2,4-dichloro-phenyl)-propionic acid methyl ester hydrochloride as a white solid. This ester was coupled with 4-chloro-2-(2,6-difluoro-benzenesulfonylamino)-benzoic acid as in EXAMPLE 1, Part C. The resulting methyl ester was hydrolyzed as in EXAMPLE 2, Part E, to afford title compound. HPLC: RT=10.20 min. MS (ESI−): mass calcd. for C22H15Cl3F2N2O5S, 563.8; m/z found, 563 [M−H]−. 1H NMR (400 MHz, acetone-d6): 8.56 (d, J=8.1, 1H), 7.82 (d, J=8.6, 1H), 7.77-7.71 (m, 1H), 7.70 (d, J=2.0, 1H), 7.50-7.48 (m, 2H), 7.31 (dd, J=8.3, 2.1, 1H), 7.22-7.14 (m, 3H), 5.08-5.00 (m, 1H), 3.62-3.51 (m, 1H), 3.34-3.21 (m, 1H).
Reaction SMILES: [OH:1][CH2:2][CH2:3][CH2:4][N:5]1[CH2:10][CH2:9][CH:8]([C:11]2[CH:12]=[C:13]([NH:17][C:18](=[O:22])[CH:19]([CH3:21])[CH3:20])[CH:14]=[CH:15][CH:16]=2)[CH2:7][CH2:6]1.[CH3:23][C:24]1[O:28][N:27]=[C:26]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[C:25]=1[C:35](Cl)=[O:36]>>[CH3:23][C:24]1[O:28][N:27]=[C:26]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[C:25]=1[C:35]([O:1][CH2:2][CH2:3][CH2:4][N:5]1[CH2:10][CH2:9][CH:8]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([NH:17][C:18](=[O:22])[CH:19]([CH3:20])[CH3:21])[CH:12]=2)[CH2:7][CH2:6]1)=[O:36]
Reactant: Cc1onc(-c2ccccc2)c1C(=O)Cl
Reactant: CC(C)C(=O)Nc1cccc(C2CCN(CCCO)CC2)c1
Product: Cc1onc(-c2ccccc2)c1C(=O)OCCCN1CCC(c2cccc(NC(=O)C(C)C)c2)CC1

Procedure:
Prepared by Procedure Q1 and Scheme C2 (TEA) using N-{3-[1-(3-hydroxypropyl)-4-piperidinyl]phenyl}-2-methylpropanamide and 5-methyl-3-phenyl-4-isoxazolecarbonyl chloride: ESMS m/e: 490.3 (M+H)+.
Reaction SMILES: [Zr:1].[C:2]([OH:6])(=[O:5])[CH:3]=[CH2:4]>>[C:2]([O-:6])(=[O:5])[CH:3]=[CH2:4].[C:2]([O-:6])(=[O:5])[CH:3]=[CH2:4].[C:2]([O-:6])(=[O:5])[CH:3]=[CH2:4].[C:2]([O-:6])(=[O:5])[CH:3]=[CH2:4].[Zr+4:1]
Reactant: C=CC(=O)O
Reactant: [Zr]
Product: C=CC(=O)[O-]
Product: [Zr+4]
Temperature: 35 °C

Procedure:
Into the flask described hereinabove there were placed 1,021.3 g of zirconium tetrabutylate to which 767.5 grams of acrylic acid were added during 8 minutes at room temperature (25° C.). The procedure was as set forth hereinabove. Owing to the reaction heat, the temperature increased to 35° C. The resultant product was a white, solid substance. The rotary evaporator heating then was switched on and gradually heated to 90° C. At the same time the vacuum was gradually adjusted to 20 mbar. The butanol was thereby expelled yielding a white powder.
Reaction SMILES: [Cl:1][CH2:2][C:3]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:4].[CH3:11][O:12][C:13]1[N:18]=[CH:17][C:16]([CH:19]([NH:31][C:32]2[CH:33]=[C:34]([CH:40]=[CH:41][CH:42]=2)[C:35]([O:37][CH2:38][CH3:39])=[O:36])[C:20](=[O:30])[O:21][C@@H:22]2[CH:27]3[CH2:28][CH2:29][N:24]([CH2:25][CH2:26]3)[CH2:23]2)=[CH:15][CH:14]=1>CCOC(C)=O>[Cl-:1].[CH2:38]([O:37][C:35]([C:34]1[CH:33]=[C:32]([NH:31][CH:19]([C:16]2[CH:17]=[N:18][C:13]([O:12][CH3:11])=[CH:14][CH:15]=2)[C:20]([O:21][C@@H:22]2[CH:27]3[CH2:28][CH2:29][N+:24]([CH2:2][C:3](=[O:4])[C:5]4[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=4)([CH2:25][CH2:26]3)[CH2:23]2)=[O:30])[CH:42]=[CH:41][CH:40]=1)=[O:36])[CH3:39]
Reactant: O=C(CCl)c1ccccc1
Reactant: CCOC(=O)c1cccc(NC(C(=O)O[C@H]2CN3CCC2CC3)c2ccc(OC)nc2)c1
Solvent: CCOC(C)=O
Product: CCOC(=O)c1cccc(NC(C(=O)O[C@H]2C[N+]3(CC(=O)c4ccccc4)CCC2CC3)c2ccc(OC)nc2)c1
Product: [Cl-]
Temperature: 25 °C
Reaction time: 8 h
Yield: 40.2 %

Procedure:
2-Chloro-1-phenylethanone (17.6 mg, 0.11 mmol) was added to a solution of ethyl 3-(1-(6-methoxypyridin-3-yl)-2-oxo-2-((R)-quinuclidin-3-yloxy)ethylamino)benzoate (C65) (50 mg, 0.11 mmol) in EtOAc (2 ml). The reaction mixture was stirred at room temperature overnight, and then the solvent was evaporated to dryness. The residue was triturated with Et2O and then purified by preparative HPLC (Eluent: CH3CN/H2O) to obtain (3R)-3-(2-(3-(ethoxycarbonyl)phenylamino)-2-(6-methoxypyridin-3-yl)acetoxy)-1-(2-oxo-2-phenylethyl)-1-azoniabicyclo[2.2.2]octane chloride (26.3 mg, 38.9% yield).
Reaction SMILES: C([O:4][C:5]1[CH:19]=[CH:18][C:17]([C:20]#[C:21][Si](C)(C)C)=[CH:16][C:6]=1[C:7]([C:9]1[CH:14]=[CH:13][C:12]([CH3:15])=[CH:11][CH:10]=1)=[O:8])(=O)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>O1CCCC1.O>[C:20]([C:17]1[CH:18]=[CH:19][C:5]([OH:4])=[C:6]([CH:16]=1)[C:7]([C:9]1[CH:10]=[CH:11][C:12]([CH3:15])=[CH:13][CH:14]=1)=[O:8])#[CH:21]
Reactant: CC(=O)Oc1ccc(C#C[Si](C)(C)C)cc1C(=O)c1ccc(C)cc1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: O
Solvent: C1CCOC1
Product: C#Cc1ccc(O)c(C(=O)c2ccc(C)cc2)c1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To a solution of 100 mg (0.3 mmol) of 2-acetoxy-5-trimethylsilanylethynyl-4'-methylbenzophenone (Compound X) in 5 mL of tetrahydrofuran (under a blanket of argon) was added 0.86 mL (0.86 mmol) of tetrabutylammonium fluoride (1M in tetrahydrofuran). The resultant yellow solution was stirred at ambient temperature for 30 minutes, diluted with water (1 mL), extracted between ethyl ether and 10% HCl (aq.) solution, the layers separated and the aqueous phase washed with ethyl ether. The organic phases were combined, dried over MgSO4, filtered and concentrated in vacuo. Purification by flash chromatography (silica, 3% ethyl acetate in hexane) gave the title compound as an oil.
Reaction SMILES: [CH2:1]([CH:8]([C:14](=O)[CH3:15])[C:9]([O:11]CC)=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[C:18](=[NH:23])([NH2:22])[CH2:19][CH2:20][CH3:21].C[O-].[Na+].CO.C(OCC)(=O)C>CO.O>[CH2:1]([C:8]1[C:9](=[O:11])[NH:23][C:18]([CH2:19][CH2:20][CH3:21])=[N:22][C:14]=1[CH3:15])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CCOC(=O)C(Cc1ccccc1)C(C)=O
Reactant: CCCC(=N)N
Agent: C[O-]
Agent: Cl
Agent: [Na+]
Solvent: O
Solvent: CO
Solvent: CCOC(C)=O
Product: CCCc1nc(C)c(Cc2ccccc2)c(=O)[nH]1
Temperature: 25 °C
Reaction time: 24 h

Procedure:
To a solution of ethyl 2-benzyl-3-oxobutanoate (2.13 mL) and butanimidamide hydrochloride (2.05 g) in methanol (50 mL) was added 28% sodium methoxide-methanol solution (5.8 g), and the mixture was stirred at room temperature for 24 hr. Ethyl acetate and water were added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated and the residue was purified by silica gel column chromatography to give the title compound as a pale-yellow viscous substance (1.61 g, 66%).
Reaction SMILES: [CH3:1][C:2]1[NH:3][CH:4]=[CH:5][N:6]=1.Cl[C:8]1[N:9]=[C:10]([NH:21][CH2:22][CH2:23][C:24]2[CH:29]=[CH:28][C:27]3[O:30][CH2:31][O:32][C:26]=3[CH:25]=2)[C:11]2[CH:16]=[C:15]([C:17]([F:20])([F:19])[F:18])[S:14][C:12]=2[N:13]=1>>[CH3:1][C:2]1[N:3]([C:8]2[N:9]=[C:10]([NH:21][CH2:22][CH2:23][C:24]3[CH:29]=[CH:28][C:27]4[O:30][CH2:31][O:32][C:26]=4[CH:25]=3)[C:11]3[CH:16]=[C:15]([C:17]([F:18])([F:20])[F:19])[S:14][C:12]=3[N:13]=2)[CH:4]=[CH:5][N:6]=1
Reactant: Cc1ncc[nH]1
Reactant: FC(F)(F)c1cc2c(NCCc3ccc4c(c3)OCO4)nc(Cl)nc2s1
Product: Cc1nccn1-c1nc(NCCc2ccc3c(c2)OCO3)c2cc(C(F)(F)F)sc2n1

Procedure:
Following the procedure of Example 97, the reaction of 2-methylimidazole with 2-chloro-6-trifluoromethyl-4-(3,4-methylenedioxyphenethylamino)-thieno-[2,3-d]-pyrimidine gives 2-(2-methylimidazol-1-yl)-6-trifluoromethyl-4-(3,4-methylenedioxyphenethylamino)-thieno-[2,3-d]-pyrimidine.
Reaction SMILES: Cl.[Br:2][C:3]1[CH:8]=[CH:7][C:6]([NH:9][NH2:10])=[CH:5][CH:4]=1.[Br:11][C:12]1[CH:19]=[CH:18][C:15]([CH2:16]Br)=[CH:14][CH:13]=1>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C(Cl)Cl>[Br:11][C:12]1[CH:19]=[CH:18][C:15]([CH2:16][N:9]([C:6]2[CH:7]=[CH:8][C:3]([Br:2])=[CH:4][CH:5]=2)[NH2:10])=[CH:14][CH:13]=1
Reactant: NNc1ccc(Br)cc1
Reactant: BrCc1ccc(Br)cc1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: Cl
Agent: [Br-]
Solvent: ClCCl
Product: NN(Cc1ccc(Br)cc1)c1ccc(Br)cc1

Procedure:
4-Bromophenylhydrazine hydrochloride (30 g, 134 mmol), p-bromobenzyl bromide (40 g, 161 mmol), disopropylethylamine (43 g, 335 mmol) and tetrabutylammonium bromide (13 g, 40 mmol) were stirred together in 400 mL of CH2Cl2 at r.t. overnight. The mixture was then washed with H2O, dried over MgSO4 and the title product was purified by flash chromatography on silica using EtOAc:hexane (30:70) and by a swish in hexanes. Yield 34 g (71%).
Reaction SMILES: [O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[NH:3][C:2]1=[O:10].Br[CH2:12][CH2:13][NH:14][C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18].CC(C)([O-])C.[K+].[I-].[K+]>CN(C=O)C>[O:10]=[C:2]1[N:3]([CH2:12][CH2:13][NH:14][C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[C:4]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=2[O:1]1
Reactant: CC(C)(C)OC(=O)NCCBr
Reactant: O=c1[nH]c2ccccc2o1
Agent: CC(C)(C)[O-]
Agent: [I-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)NCCn1c(=O)oc2ccccc21
Temperature: 80 °C
Reaction time: 8 h
Yield: 65.7 %

Procedure:
Combine 2-(3H)-benzoxazolone (0.4 g, 2.9 mmol), tert-butyl 2-bromoethylcarbamate (715.14 mg, 3.19 mmol), potassium tert-butoxide (508.7 mg, 4.35 mmol), potassium iodide (0.1 g, 0.6 mmol) in DMF (6 mL). Heat to 80° C. and stir the mixture overnight. Filter; collect the filtrate; and purify via HPLC conditions M (See below) to provide the title compound (0.53 g, 65.6%) as an oily solid. MS (m/z): 223 (M-tBu+1).
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:12][CH2:11][C@H:10]([CH2:13][NH:14][C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[CH2:9]2)=[C:4]([F:22])[CH:3]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[CH3:36][C:37]([CH3:39])=O>>[F:22][C:4]1[CH:3]=[C:2]([NH:1][CH:37]([CH3:39])[CH3:36])[CH:7]=[CH:6][C:5]=1[N:8]1[CH2:12][CH2:11][C@H:10]([CH2:13][NH:14][C:15](=[O:21])[O:16][C:17]([CH3:18])([CH3:19])[CH3:20])[CH2:9]1
Reactant: CC(C)(C)OC(=O)NC[C@H]1CCN(c2ccc(N)cc2F)C1
Reactant: CC(C)=O
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Product: CC(C)Nc1ccc(N2CC[C@H](CNC(=O)OC(C)(C)C)C2)c(F)c1

Procedure:
tert-Butyl (R)-[1-(4-amino-2-fluorophenyl)pyrrolidin-3-yl]methylcarbamate was alkylated with acetone using triacetoxyborohydride as reducing agent by method N. This resulted in the product with the molecular weight of 351.47 (C19H30FN3O2); MS (ESI): 352 (M+H+).
Reaction SMILES: [Cl:1][CH2:2][C:3]1[C:16]2[CH:15]=[CH:14][C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[C:7]=2[CH:6]=[CH:5][CH:4]=1.[N:17]1[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[CH:20]=[CH:19][CH:18]=1>C(O)(C)C>[Cl-:1].[C:3]1([CH2:2][N+:17]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[CH:20]=[CH:19][CH:18]=2)[C:16]2[CH:15]=[CH:14][C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[C:7]=2[CH:6]=[CH:5][CH:4]=1
Reactant: c1ccc2ncccc2c1
Reactant: ClCc1cccc2c1ccc1ccccc12
Solvent: CC(C)O
Product: [Cl-]
Product: c1ccc2c(c1)ccc1c(C[n+]3cccc4ccccc43)cccc12
Temperature: 125 °C

Procedure:
90 g. of the chloromethylphenanthrene prepared above was placed in a reaction vessel, along with 61.5 g. of crude quinoline. The resulting mixture was then stirred and heated to a temperature of 125° C. A total of 101 g. of isopropanol was weighed out and a portion of this was added to the reaction mixture to permit temperature maintenance of the reaction mixture by refluxing of the isopropanol portion. After the mixture had been held at 125° C. temperature for about 3 hours, the material was cooled to room temperature and the remainder of the isopropanol was added. This resulted in a 60% isopropanol solution of N-(phenanthrylmethyl) quinolinium chloride.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:29]=[C:30]([N:32]2[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]2)[CH:31]=1)[C:5]([NH:7][C:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11]([O:18][C:19]2[CH:24]=[CH:23][N:22]=[C:21](S(C)(=O)=O)[N:20]=2)=[CH:10][CH:9]=1)=[O:6].[NH:38]1[CH2:43][CH2:42][CH:41]([OH:44])[CH2:40][CH2:39]1>>[F:1][C:2]1[CH:3]=[C:4]([CH:29]=[C:30]([N:32]2[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]2)[CH:31]=1)[C:5]([NH:7][C:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11]([O:18][C:19]2[CH:24]=[CH:23][N:22]=[C:21]([N:38]3[CH2:43][CH2:42][CH:41]([OH:44])[CH2:40][CH2:39]3)[N:20]=2)=[CH:10][CH:9]=1)=[O:6]
Reactant: CS(=O)(=O)c1nccc(Oc2ccc(NC(=O)c3cc(F)cc(N4CCCCC4)c3)c3ccccc23)n1
Reactant: OC1CCNCC1
Product: O=C(Nc1ccc(Oc2ccnc(N3CCC(O)CC3)n2)c2ccccc12)c1cc(F)cc(N2CCCCC2)c1

Procedure:
Compound is prepared from 3-fluoro-N-[4-(2-methanesulfonyl-pyrimidin-4-yloxy)-naphthalen-1-yl]-5-piperidin-1-yl-benzamide and piperidin-4-ol according to conditions described in general procedure C. Mp: 182-184° C.; 1H NMR (400 MHz, DMSO-d6) δ 1.15 (bs, 2 H), 1.58 (s, 8 H), 3.00 (bs, 2 H), 3.27 (s, 4 H), 3.61 (m, 1 H), 3.95 (bs, 2 H), 4.64 (d, J=4.0 Hz, 1 H), 6.19 (d, J=5.5 Hz, 1 H), 6.96 (d, J=12.8 Hz, 1 H), 7.15 (d, J=8.8 Hz, 1 H), 7.40 (d, J=8.4 Hz, 1 H), 7.46 (s, 1 H), 7.55-7.59 (m, 3 H), 7.82 (d, J=8.0 Hz, 1 H), 7.97 (d, J=8.4 Hz, 1 H), 8.22-8.24 (m, 1 H), 10.43 (s, 1 H).
Reaction SMILES: [CH3:1][S:2][CH2:3][CH2:4][CH:5]([N:10]([CH2:29][CH:30]1[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]1)[C:11]([CH2:13][CH2:14][CH2:15][CH2:16][O:17][C:18]1[CH:19]=[C:20]2[C:25](=[CH:26][CH:27]=1)[NH:24][C:23](=[O:28])[CH:22]=[CH:21]2)=[O:12])[C:6](OC)=O.B.[Na].Cl.C([OH:41])C>>[CH3:1][S:2][CH2:3][CH2:4][C:5]([CH3:6])([N:10]([CH2:29][CH:30]1[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]1)[C:11]([CH2:13][CH2:14][CH2:15][CH2:16][O:17][C:18]1[CH:19]=[C:20]2[C:25](=[CH:26][CH:27]=1)[NH:24][C:23](=[O:28])[CH:22]=[CH:21]2)=[O:12])[OH:41]
Reactant: CCO
Reactant: COC(=O)C(CCSC)N(CC1CCCCC1)C(=O)CCCCOc1ccc2[nH]c(=O)ccc2c1
Agent: B
Agent: Cl
Agent: [Na]
Product: CSCCC(C)(O)N(CC1CCCCC1)C(=O)CCCCOc1ccc2[nH]c(=O)ccc2c1
Reaction time: 2 h

Procedure:
In 80 ml of ethanol is dissolved 1.6 g of 6-{4-[N-(3-methylthio-1-methoxycarbonylpropyl)-N-cyclohexylmethylaminocarbonyl]butoxy}carbostyril. Thereto is added 3.2 g of sodium boron hydride. The mixture is stirred for 2 hours at 50°-60° C. The reaction mixture is neutralized with diluted hydrochloric acid and concentrated. The residue is extracted with a mixture of chloroform and methanol (10:1). The extract is purified by means of a silica gel column chromatography (eluant; chloroform:methanol=20:1). The resulting residue is recrystallized from a mixed solvent of dichloromethane-ethyl acetate-diethyl ether to obtain 0.78 g of 6-{4-[N-(3-methylthio-1-hydroxy-methylpropyl)-N-cyclohexylmethylaminocarbonyl]butoxy}carbostyril.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([N+:11]([O-:13])=[O:12])[CH:10]=1)[C:5]([OH:7])=[O:6].[C:14]1(C)[CH:19]=CC(S(O)(=O)=O)=C[CH:15]=1.C(O)C=C>C(N(CC)CC)C>[F:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([N+:11]([O-:13])=[O:12])[CH:10]=1)[C:5]([O:7][CH2:19][CH:14]=[CH2:15])=[O:6]
Reactant: Cc1ccc(S(=O)(=O)O)cc1
Reactant: O=C(O)c1cc(F)cc([N+](=O)[O-])c1
Solvent: C=CCO
Solvent: CCN(CC)CC
Product: C=CCOC(=O)c1cc(F)cc([N+](=O)[O-])c1
Reaction time: 16 h

Procedure:
3-Fluoro-5-nitrobenzoic acid (3 g, 16.2 mM), p-toluenesulfonic acid (1.54 g, 8.1 mM), and allyl alcohol (50 ml) were heated to reflux, passing the distillate through 3å molecular sieves, for 16 hours. After cooling, the mixture was neutralised with triethylamine, and solvent removed. The residue was dissolved in ethyl acetate, washed with 2M hydrochloric acid, aqueous NaHCO3, and brine, and dried over MgSO4. Crude product was purified by chromatography on silica, using a gradient elution from dichloromethane to ethyl acetate/dichloromethane (3:1), to give allyl 3-fluoro-5-nitrobenzoate. Nmr (CDCl3): δ 4.89 (dt, 2H); 5.33-5.49 (m, 2H); 5.95-6.15 (m, 1H); 8.11 (m, 2H); 8.70 (t, 1H).
Reaction SMILES: [CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[OH:11].CO.[CH:14]1[CH2:18][CH:17]=[CH:16][CH:15]=1.C1COCC1>CC(CC(C)=O)C>[CH:18]1([C:1]2[C:10]3[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=3)[CH:4]=[CH:3][C:2]=2[OH:11])[CH2:17][CH2:16][CH:15]=[CH:14]1
Reactant: Oc1ccc2ccccc2c1
Reactant: C1=CCC=C1
Solvent: CC(=O)CC(C)C
Solvent: CO
Solvent: C1CCOC1
Product: Oc1ccc2ccccc2c1C1C=CCC1
Temperature: 25 °C

Procedure:
Into a 2-liter flask having a stirrer, a condenser and a thermometer, 144 g of 2-naphthol, 200 g of methanol and 40 g of PTS were introduced, and a solution of mixture of 66 g of cyclopentadiene and 60 g of methanol was added dropwise over a period of 3 hours while stirring the mixture at room temperature, followed by further stirring for 4 hours at room temperature. To the reaction solution thus obtained, THF and MIBK were added, and the resultant solution was washed with 200 ml of an aqueous 10% sodium hydroxide solution five times, and thereafter further washed with water until it turned neutral, followed by removal of the solvent using an evaporator. The results of analysis by GPC thereof are shown in FIG. 11. Its yield determined by GPC was 90% (area ratio). An NMR spectrum of the 1-(2-penten-1-yl)-2-naphthol obtained is shown in FIG. 12.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][C:4]([N:7]2[CH2:12][CH2:11][NH:10][CH2:9][CH2:8]2)=[CH:3][CH:2]=1.Br[CH2:14][C:15]1[CH:20]=[CH:19][C:18]([CH2:21][CH2:22][CH2:23][C:24]([O:26][CH3:27])=[O:25])=[CH:17][CH:16]=1>C(#N)C>[N:1]1[CH:6]=[CH:5][C:4]([N:7]2[CH2:8][CH2:9][N:10]([CH2:14][C:15]3[CH:16]=[CH:17][C:18]([CH2:21][CH2:22][CH2:23][C:24]([O:26][CH3:27])=[O:25])=[CH:19][CH:20]=3)[CH2:11][CH2:12]2)=[CH:3][CH:2]=1
Reactant: c1cc(N2CCNCC2)ccn1
Reactant: COC(=O)CCCc1ccc(CBr)cc1
Solvent: CC#N
Product: COC(=O)CCCc1ccc(CN2CCN(c3ccncc3)CC2)cc1
Temperature: 30 °C

Procedure:
1-(4-Pyridyl)piperazine (1.63 g) was dissolved in warm acetontrile (25 ml), the solution cooled to 30° C. and with stirring, a solution of methyl 4-(4-bromomethylphenyl)butyrate in acetonitrile (5 ml) added. After 30 minutes the resulting precipitate was removed by filtration and the filtrate concentrated in vacuo to give a yellow oil. Purification by flash chromatography on silica, eluting with 0 to 4% v/v methanol/dichloromethane gave a solid. Trituration with ether and removal of the insoluble solid gave a clear solution. Concentration of this solution gave the title compound, 0.90 g, as a white fluffy solid: m.p. 126°-127° C.; NMR (d6DMSO) δ8.14(2H,d), 7.24(2H,d), 7.14(2H,d), 6.77(2H,d), 3.59(3H,s), 3.48(2H,s), 3.30(4H,t), 2.59(2H,t), 2.47(4H,t), 2.32(2H,t), 1.63(2H,m); m/e 354 (M+H)+ ; calculated for C21H27N3O2 0.25H2O: C, 70.4; H, 7.7; N, 11.7. found: C, 70.6; H, 7.6; N, 11.7%.
Reaction SMILES: Cl[C:2]1[C:7]([C:8]#[N:9])=[CH:6][N:5]=[C:4]([C:10]2[CH:15]=[CH:14][C:13]([O:16][CH2:17][CH3:18])=[CH:12][CH:11]=2)[N:3]=1>[Zn].O1CCOCC1>[C:8]([C:7]1[CH:6]=[N:5][C:4]([C:10]2[CH:15]=[CH:14][C:13]([O:16][CH2:17][CH3:18])=[CH:12][CH:11]=2)=[N:3][CH:2]=1)#[N:9]
Reactant: CCOc1ccc(-c2ncc(C#N)c(Cl)n2)cc1
Agent: [Zn]
Solvent: C1COCCO1
Product: CCOc1ccc(-c2ncc(C#N)cn2)cc1

Procedure:
5.0 G. of 4-chloro-5-cyano-2-(4-ethoxyphenyl)-pyrimidine are reacted in 250 ml. of 50% dioxane with 22.2 g. of pre-treated zinc dust and worked up after the reaction in a manner analogous to that described in Example 13. There is obtained 5-cyano-2-(4-ethoxyphenyl)-pyrimidine as colorless crystals having a melting point of 152.6°-153.0° C. which on cooling are nematic (mono-tropic) at 149.7° C.
Reaction SMILES: [C:1]([O:5][CH:6]([C:11]1[C:12]([C:21]2[CH:26]=[CH:25][C:24]([CH3:27])=[CH:23][CH:22]=2)=[C:13]2[CH:20]=[CH:19][NH:18][C:14]2=[N:15][C:16]=1[CH3:17])[C:7]([O:9]C)=[O:8])([CH3:4])([CH3:3])[CH3:2].Br[CH2:29][C:30]1[CH:35]=[CH:34][C:33]([F:36])=[C:32]([C:37]([F:40])([F:39])[F:38])[CH:31]=1>>[C:1]([O:5][CH:6]([C:11]1[C:12]([C:21]2[CH:26]=[CH:25][C:24]([CH3:27])=[CH:23][CH:22]=2)=[C:13]2[CH:20]=[CH:19][N:18]([CH2:29][C:30]3[CH:35]=[CH:34][C:33]([F:36])=[C:32]([C:37]([F:40])([F:38])[F:39])[CH:31]=3)[C:14]2=[N:15][C:16]=1[CH3:17])[C:7]([OH:9])=[O:8])([CH3:3])([CH3:2])[CH3:4]
Reactant: COC(=O)C(OC(C)(C)C)c1c(C)nc2[nH]ccc2c1-c1ccc(C)cc1
Reactant: Fc1ccc(CBr)cc1C(F)(F)F
Product: Cc1ccc(-c2c(C(OC(C)(C)C)C(=O)O)c(C)nc3c2ccn3Cc2ccc(F)c(C(F)(F)F)c2)cc1

Procedure:
The title compound was prepared from methyl 2-(tert-butoxy)-2-(6-methyl-4-(p-tolyl)-1H-pyrrolo[2,3-b]pyridin-5-yl)acetate and 4-(bromomethyl)-1-fluoro-2-(trifluoromethyl)benzene in a manner similar to that described in Example 25 as a yellow solid. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm=7.67-7.58 (m, 2 H), 7.48-7.38 (m, 2 H), 7.34 (d, J=7.8 Hz, 2 H), 7.16 (t, J=9.3 Hz, 1 H), 7.05 (d, J=3.5 Hz, 1 H), 6.26 (d, J=3.5 Hz, 1H), 5.60-5.45 (m, 3 H), 2.75 (s, 3 H), 2.47 (s, 3 H), 0.95 (s, 9 H); LCMS (m/z) ES+=529 (M+1).