Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:37]=[CH:36][CH:35]=[CH:34][C:4]=1[CH2:5][N:6]1[CH2:10][CH2:9][C:8]([CH2:18][C:19]2[CH:24]=[C:23]([C:25]([F:28])([F:27])[F:26])[CH:22]=[C:21]([C:29]([F:32])([F:31])[F:30])[CH:20]=2)([CH2:11][CH2:12]OS(C)(=O)=O)[C:7]1=[O:33].I.[CH2:39]([O:41][CH2:42][CH2:43][N:44]1[C:48]2[CH:49]=[CH:50][CH:51]=[CH:52][C:47]=2[N:46]=[C:45]1[N:53]1[CH2:59][CH2:58][CH2:57][NH:56][CH2:55][CH2:54]1)[CH3:40]>>[CH3:1][O:2][C:3]1[CH:37]=[CH:36][CH:35]=[CH:34][C:4]=1[CH2:5][N:6]1[CH2:10][CH2:9][C:8]([CH2:11][CH2:12][N:56]2[CH2:57][CH2:58][CH2:59][N:53]([C:45]3[N:44]([CH2:43][CH2:42][O:41][CH2:39][CH3:40])[C:48]4[CH:49]=[CH:50][CH:51]=[CH:52][C:47]=4[N:46]=3)[CH2:54][CH2:55]2)([CH2:18][C:19]2[CH:20]=[C:21]([C:29]([F:31])([F:30])[F:32])[CH:22]=[C:23]([C:25]([F:27])([F:26])[F:28])[CH:24]=2)[C:7]1=[O:33]
Reactant: COc1ccccc1CN1CCC(CCOS(C)(=O)=O)(Cc2cc(C(F)(F)F)cc(C(F)(F)F)c2)C1=O
Reactant: CCOCCn1c(N2CCCNCC2)nc2ccccc21
Agent: I
Product: CCOCCn1c(N2CCCN(CCC3(Cc4cc(C(F)(F)F)cc(C(F)(F)F)c4)CCN(Cc4ccccc4OC)C3=O)CC2)nc2ccccc21

Procedure:
Prepare by the method of Example 7.6 using 1-(2-methoxybenzyl)-3-(3 5-di(trifluoromethyl)phenylmethyl)-3-(2-methanesulfonyloxyethyl)-2-oxopyrrolidine and 4-(1-(2-ethoxyethyl)-1H-benzimidazol-2-yl)[1,4]diazepane hydriodic acid salt to give the title compound: Rf=0.54 (silica gel, 5% methanol/dichloromethane/0.5% concentrated aqueous ammonia).
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][C:8]=2[C:10]([OH:12])=O)[CH:3]=[CH:2]1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C(N(CC)C(C)C)(C)C.[C:44]([C:48]1[CH:67]=[CH:66][C:51]([CH2:52][NH:53][CH2:54][CH2:55][C:56]2[CH:61]=[CH:60][CH:59]=[C:58]([O:62][CH:63]([F:65])[F:64])[CH:57]=2)=[CH:50][CH:49]=1)([CH3:47])([CH3:46])[CH3:45]>CN(C=O)C.O>[C:44]([C:48]1[CH:67]=[CH:66][C:51]([CH2:52][N:53]([CH2:54][CH2:55][C:56]2[CH:61]=[CH:60][CH:59]=[C:58]([O:62][CH:63]([F:65])[F:64])[CH:57]=2)[C:10]([C:8]2[CH:7]=[CH:6][CH:5]=[C:4]3[C:9]=2[NH:1][CH:2]=[CH:3]3)=[O:12])=[CH:50][CH:49]=1)([CH3:47])([CH3:45])[CH3:46]
Reactant: CC(C)(C)c1ccc(CNCCc2cccc(OC(F)F)c2)cc1
Reactant: O=C(O)c1cccc2cc[nH]c12
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[B-](F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Solvent: O
Product: CC(C)(C)c1ccc(CN(CCc2cccc(OC(F)F)c2)C(=O)c2cccc3cc[nH]c23)cc1
Temperature: 25 °C
Reaction time: 0.08 h
Yield: 73.4 %

Procedure:
To a solution of 48 mg (0.3 mmol) of 1H-indole-7-carboxylic acid and 96 mg of TBTU (0.3 mmol) in 3 ml DMF, were added 0.26 ml (1.5 mmol) of N,N-diisopropylethyl amine. After stirring for 5 min at rt, 100 mg (0.3 mmol) of (4-tert-butyl-benzyl)-[2-(3-difluoromethoxy-phenyl)-ethyl]-amine in 2 ml DMF was added. After 2.5 h stirring at rt, the reaction mixture was diluted with 50 ml water and extracted with EtOAc (2×). The combined organic phases were washed with water and brine, dried with magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography (8 g silica gel; EtOAc/heptane 1:6) to give 105 mg colorless viscous oil (73%). MS (EI) 477.4 (M)+.
Reaction SMILES: [CH2:1]([C:5]1[CH:10]=[CH:9][C:8]([C:11]([C:13]2[C:22]3[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=3)[CH:16]=[CH:15][N:14]=2)=O)=[CH:7][CH:6]=1)[CH2:2][CH2:3][CH3:4].O.NN.[OH-].[K+]>C(O)COCCO>[CH2:1]([C:5]1[CH:10]=[CH:9][C:8]([CH2:11][C:13]2[C:22]3[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=3)[CH:16]=[CH:15][N:14]=2)=[CH:7][CH:6]=1)[CH2:2][CH2:3][CH3:4]
Reactant: CCCCc1ccc(C(=O)c2nccc3ccccc23)cc1
Agent: NN
Agent: [K+]
Agent: [OH-]
Solvent: OCCOCCO
Solvent: O
Product: CCCCc1ccc(Cc2nccc3ccccc23)cc1
Temperature: 160 °C
Reaction time: 3.5 h
Yield: 55.3 %

Procedure:
The compound of Example B3 (1.7 g, 6.0 mmol), hydrazine monohydrate (836 mg, 17 mmol), and potassium hydroxide (769 mg, 14 mmol) were added to diethylene glycol (8.5 ml), and this mixture was stirred at 80° C. for 1 hour, at 160° C. for 3.5 hours, then at 200° C. for 1 hour. The mixture was cooled to room temperature, ice water was added, and this was extracted with ethyl acetate. The extract was washed with water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to give the title compound (914 mg).
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][C:3]=1[SH:11].[OH-].[Na+].Br[CH2:15][CH2:16][Cl:17]>C(O)C.O.C(OCC)(=O)C>[Cl:17][CH2:16][CH2:15][S:11][C:3]1[CH:4]=[C:5]([N+:8]([O-:10])=[O:9])[CH:6]=[CH:7][C:2]=1[NH2:1]
Reactant: ClCCBr
Reactant: Nc1ccc([N+](=O)[O-])cc1S
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CCOC(C)=O
Solvent: CCO
Product: Nc1ccc([N+](=O)[O-])cc1SCCCl
Temperature: 25 °C
Reaction time: 3 h
Yield: 91.3 %

Procedure:
To a stirred suspension of 2-amino-5-nitrobenzenethiol (4.11 g, 24.15 mmol) in ethanol (50 mL) and water (10 mL) was added sodium hydroxide (0.966 g, 24.15 mmol). To the resulting solution was added 1-bromo-2-chloroethane (8.04 mL, 97 mmol), and the resulting mixture was stirred at room temperature for 3 hours. The mixture was then diluted with ethyl acetate and washed with saturated sodium carbonate (3×). The organic phase was dried, filtered, and concentrated, giving a dark yellow solid (5.13 g, 91%). 1H NMR (DMSO-d6) δ 8.16 (d, J=2.7 Hz, 1H), 7.97 (dd, J=9.0, 2.7 Hz, 1H), 6.94 (brs, 2H), 6.79 (d, J=9.0 Hz, 1H), 3.68 (t, J=7.2 Hz, 2H), 3.11 (t, J=7.2 Hz, 2H); ESI-MS (m/z, %): 233 (MH+, 100), 216 (79).
Reaction SMILES: Cl[CH:2]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)[CH3:3].[Cl:10][SiH:11]([Cl:13])[Cl:12]>[Cl-].C([P+](CCCC)(CCCC)CCCC)CCC>[C:3]1([CH:2]([C:4]2[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=2)[Si:11]([Cl:13])([Cl:12])[Cl:10])[CH:6]=[CH:5][CH:4]=[CH:2][CH:3]=1
Reactant: CC(Cl)c1ccccc1
Reactant: Cl[SiH](Cl)Cl
Agent: CCCC[P+](CCCC)(CCCC)CCCC
Agent: [Cl-]
Product: Cl[Si](Cl)(Cl)C(c1ccccc1)c1ccccc1
Yield: 43.8 %

Procedure:
In the same apparatus and procedure as Example 1 above, 0.14 g (0.47 mmol) of tetrabutylphosphonium chloride, 0.95 g (4.69 mmol) of 1-chloroethylbenzene, and 1.91 g (14.10 mmol) of trichlorosilane were reacted at 150° C. for 6 hrs. The resulting mixture was distilled to give 0.31 g diphenyl-1-trichlorosilylmethane (yield; 22%).
Reaction SMILES: [NH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][CH2:2]1.[Cl:11]N1C(=O)CCC1=O>CN(C=O)C>[Cl:11][C:7]1[CH:6]=[C:5]2[C:10](=[CH:9][CH:8]=1)[NH:1][CH2:2][CH2:3][CH2:4]2
Reactant: c1ccc2c(c1)CCCN2
Reactant: O=C1CCC(=O)N1Cl
Solvent: CN(C)C=O
Product: Clc1ccc2c(c1)CCCN2
Temperature: 0 °C
Reaction time: 0.75 h

Procedure:
Based on R. Nagata et al., J. Med. Chem., 1994, 37, 3956-3968, 1,2,3,4-tetrahydroquinoline (1.33 g, 10 mmol) was dissolved in DMF (15 mL) under N2 and cooled to 0° C. N-Chlorosuccinimide (1.35 g, 10 mmol) was dissolved in DMF (10 mL) under N2 and was added to the tetrahydroquinoline solution dropwise, via pressure equalizing dropping funnel, over 45 min. The reaction was stirred at 0° C. for 3 h, then quenched by pouring it into water (100 mL). This mixture was extracted with a 5:1 mixture of EtOAc:toluene, then two times with EtOAc. All of the organic extracts were washed with brine, combined, dried over Na2SO4, filtered, and concentrated, then eluted through a 17×2.5 cm column of silica gel (5%, 10% and 15% EtOAc/Hexane step gradient) giving 6-chloro-1,2,3,4-tetrahydroquinoline as a green oil.
Reaction SMILES: Cl.[SH:2][CH2:3][CH2:4][NH2:5].C(N(CC)CC)C.[C:13](Cl)(=[O:18])[C:14]([CH3:17])([CH3:16])[CH3:15].[Cl-].[NH4+]>ClCCl>[SH:2][CH2:3][CH2:4][NH:5][C:13](=[O:18])[C:14]([CH3:17])([CH3:16])[CH3:15]
Reactant: NCCS
Reactant: CC(C)(C)C(=O)Cl
Agent: Cl
Agent: [Cl-]
Agent: [NH4+]
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(C)(C)C(=O)NCCS
Temperature: 40 °C
Reaction time: 1.5 h

Procedure:
22.7 g of 2-mercaptoethylamine hydrochloride (0.2 mol) and 32.4 g of triethylamine (0.32 mol) were introduced in suspension in 130 ml of dichloromethane at 0° C.-5° C. Over the course of 30 minutes, 12.1 g of pivaloyl chloride (0.1 mol) were added dropwise. The batch was stirred at 0° C. to 5° C. for 1 hour, at 40° C. for 1.5 hours, and then at room temperature for 12 hours. 70 ml of saturated ammonium chloride solution were added and a phase separation was carried out. This was repeated twice and the organic phases were combined, dried over sodium sulfate, and freed of their solvent under reduced pressure.
Reaction SMILES: [Br:1]Br.[CH3:3][O:4][C:5]([C:7]1[CH:8]=[C:9]2[CH:19]=[CH:18][S:17][C:10]2=[N:11][C:12]=1[C:13]([O:15][CH3:16])=[O:14])=[O:6].C([O-])(=O)C.[Na+]>C(O)(=O)C.O>[Br:1][C:19]1[C:9]2[C:10](=[N:11][C:12]([C:13]([O:15][CH3:16])=[O:14])=[C:7]([C:5]([O:4][CH3:3])=[O:6])[CH:8]=2)[S:17][CH:18]=1
Reactant: BrBr
Reactant: COC(=O)c1cc2ccsc2nc1C(=O)OC
Agent: CC(=O)[O-]
Agent: [Na+]
Solvent: O
Solvent: CC(=O)O
Product: COC(=O)c1cc2c(Br)csc2nc1C(=O)OC
Temperature: 75 °C
Reaction time: 6 h

Procedure:
Bromine (0.33, 0.00206 mol) in acetic acid (8 mL) is added to a stirred solution of dimethylthieno[2,3-b]pyridine-5,6-dicarboxylate (0.5 g, 0.00187 mol) in acetic acid containing sodium acetate (0.31 g, 0.00377 mol) at 40° C. The reaction mixture is heated at 75° C. for 18 hours. Evaluation of the mixture by tlc (silica gel) indicated incomplete reaction. Additional bromine (0.33 g) in acetic acid and sodium acetate (0.31 g) is added and heating at 75° C. continued for six hours. The reaction mixture is diluted with water and extracted into ethyl acetate. The separated organic layer is dried over anhydrous MgSO4, filtered, and the filtrate concentrated to an oil which solidifies on standing. Crystallization of the crude product from ethyl acetate-hexanes yields the dimethyl 3-bromothieno[2,3-b]pyridine-5,6-dicarboxylate as white needles mp 86°-87.5° C.
Reaction SMILES: C[O:2][C:3]([C:5]1[S:35][C:8]2[N:9]=[CH:10][N:11]=[C:12]([NH:13][C:14]3[CH:19]=[CH:18][C:17]([F:20])=[CH:16][C:15]=3[O:21][C@@H:22]3[CH2:27][CH2:26][CH2:25][N:24]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:23]3)[C:7]=2[C:6]=1[CH3:36])=[O:4].[OH-].[Na+]>CO.C1COCC1>[C:31]([O:30][C:28]([N:24]1[CH2:25][CH2:26][CH2:27][C@@H:22]([O:21][C:15]2[CH:16]=[C:17]([F:20])[CH:18]=[CH:19][C:14]=2[NH:13][C:12]2[C:7]3[C:6]([CH3:36])=[C:5]([C:3]([OH:4])=[O:2])[S:35][C:8]=3[N:9]=[CH:10][N:11]=2)[CH2:23]1)=[O:29])([CH3:34])([CH3:32])[CH3:33]
Reactant: COC(=O)c1sc2ncnc(Nc3ccc(F)cc3O[C@@H]3CCCN(C(=O)OC(C)(C)C)C3)c2c1C
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CO
Product: Cc1c(C(=O)O)sc2ncnc(Nc3ccc(F)cc3O[C@@H]3CCCN(C(=O)OC(C)(C)C)C3)c12

Procedure:
A mixture of 4-[2-((R)-1-tert-Butoxycarbonyl-piperidin-3-yloxy)-4-fluoro-phenylamino]-5-methyl-thieno[2,3-d]pyrimidine-6-carboxylic acid methyl ester (1.65 g) in MeOH/THF (1:1; 20 ml) was treated with NaOH (2M; 8 ml) and heated at reflux for 10 mins. Organic solvent was removed in vacuo. HCl (2M; 8 ml) was added to pH 1 and water was added. The suspension was filtered and washed with water. The solid was suspended in EtOH and evaporated. The residue was triturated with Acetonitrile to give the desired product.
Reaction SMILES: C(ON=O)(C)(C)C.Br[CH:9]1[CH2:14][CH2:13][CH2:12][CH:11]=[CH:10]1.[N+:15]([C:18]1[CH:19]=[C:20]([CH:22]=[C:23]([N+:25]([O-:27])=[O:26])[CH:24]=1)N)([O-:17])=[O:16]>CC#N>[N+:15]([C:18]1[CH:19]=[C:20]([CH:14]2[CH2:13][CH2:12][CH2:11][CH:10]=[CH:9]2)[CH:22]=[C:23]([N+:25]([O-:27])=[O:26])[CH:24]=1)([O-:17])=[O:16]
Reactant: Nc1cc([N+](=O)[O-])cc([N+](=O)[O-])c1
Reactant: BrC1C=CCCC1
Agent: CC(C)(C)ON=O
Solvent: CC#N
Product: O=[N+]([O-])c1cc(C2C=CCCC2)cc([N+](=O)[O-])c1
Temperature: 26.5 °C
Reaction time: 1 h
Yield: 12.1 %

Procedure:
To a solution of t-butylnitrite (119 μl, 1.0 mmol) and 3-bromocyclohexene (860 μl, 7.5 mmol) in CH3CN (0.5 ml), 3,5-dinitroaniline (92 mg, 0.5 mmol) was added during 10 minutes, while maintaining the temperature of the reaction mixture at 23-30° C. After stirring for one hour at room temperature the volatile material in the reaction mixture was removed at reduced pressure. Column chromatography (heptane-ethyl acetate 23:2) followed by preparative HPLC gave 15 mg (12%) of 3-(3,5-dinitrophenyl)cyclohexene as bright yellow crystals. 1H NMR (CDCl3, 300 MHz) δ 8.90, (t, 1H, J=2.1 Hz), 8.42, (d, 2H, J=2.1 Hz), 6.19-6.06, (m, 1H), 5.74-5.66, (m, 1H), 3.67, (m, 1H), 2.25-2.07, (m, 3H), 1.80-1.51, (m, 3H).
Reaction SMILES: [F:1][C:2]1[CH:3]=[CH:4][C:5]([C:11]([F:14])([F:13])[F:12])=[C:6]([CH:10]=1)[C:7]([OH:9])=[O:8].[Si](C=[N+]=[N-])(C)(C)[CH3:16]>C(Cl)(Cl)Cl.CO.CCOCC>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:11]([F:12])([F:13])[F:14])=[C:6]([CH:10]=1)[C:7]([O:9][CH3:16])=[O:8]
Reactant: C[Si](C)(C)C=[N+]=[N-]
Reactant: O=C(O)c1cc(F)ccc1C(F)(F)F
Solvent: ClC(Cl)Cl
Solvent: CO
Solvent: CCOCC
Product: COC(=O)c1cc(F)ccc1C(F)(F)F
Reaction time: 1 h

Procedure:
To a solution of 5-fluoro-2-(trifluoromethyl)benzoic acid (2.0 g, 9.62 mmol, Aldrich) in a mixture of chloroform and methanol (1:1, 40 ml) was added a 2 M solution of TMS-diazomethane in ether (approximately 8 ml) dropwise, in portions over about 1 h, allowing the solution to cool down between additions. The solution was evaporated in vacuo. To the residue was added chloroform (approximately 40 ml) and the solvent removed in vacuo to give methyl 5-fluoro-2-(trifluoromethyl)benzoate as a colourless slightly cloudy oil (2.09 g). To a stirred solution of phenol (1.06 g, 11.3 mmol, Aldrich) in DMSO (8 ml) under nitrogen was added potassium t-butoxide (1.27 g, 11.3 mmol) and the mixture stirred to dissolve. To the mixture was added methyl 5-fluoro-2-(trifluoromethyl)benzoate (2.09 g, 9.41 mmol) in DMSO (2 ml) and the mixture allowed to stand for one week. To the dark coloured mixture was added dilute aqueous sodium bicarbonate and the mixture extracted with ether four times. The combined organic extracts were dried (Na2SO4), filtered and the solvent removed in vacuo to leave a yellow oil (approximately 2 g). The residue was purified on silica 50 g using 0-100% DCM-cyclohexane. The appropriate fractions were combined and evaporated in vacuo to give methyl 5-(phenyloxy)-2-(trifluoromethyl)benzoate as a colourless oil (0.516 g).
Reaction SMILES: [C:1]1([C:7]2([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH:11]3[CH2:12][NH:13][CH2:14][CH2:15][N:10]3[C:9](=[O:16])[O:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(N(CC)CC)C.[C:30]1(=[O:36])[O:35][C:33](=[O:34])[CH2:32][CH2:31]1.C(OCC)(=O)C>O1CCCC1>[O:36]=[C:30]([N:13]1[CH2:14][CH2:15][N:10]2[C:9](=[O:16])[O:8][C:7]([C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)([C:17]3[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=3)[CH:11]2[CH2:12]1)[CH2:31][CH2:32][C:33]([OH:35])=[O:34]
Reactant: O=C1OC(c2ccccc2)(c2ccccc2)C2CNCCN12
Reactant: O=C1CCC(=O)O1
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: O=C(O)CCC(=O)N1CCN2C(=O)OC(c3ccccc3)(c3ccccc3)C2C1
Temperature: 25 °C
Reaction time: 2 h
Yield: 50.2 %

Procedure:
To a solution of hexahydro-1,1-diphenyl-3H-oxazolo[3,4-a]pyrazin-3-one (0.15 g, 0.50 mmol) in tetrahydrofuran (10 mL) were added triethylamine (0.14 mL, 1.0 mmol) and succinic anhydride (55 mg, 0.55 mmol), and the mixture was stirred at room temperature for 2 hours. To the reaction solution was added ethyl acetate, and the resulting mixture was washed with 2 M hydrochloric acid, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified with silica gel column chromatography (hexane:ethyl acetate=1:1 to ethyl acetate). The fractions were concentrated, and to the residue was added diethyl ether. The resulting crystals were collected by filtration and washed with diethyl ether to obtain the title compound (99 mg, yield 50%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:10]=[C:9]([O:11][CH3:12])[CH:8]=[CH:7][C:4]=1[CH:5]=O.[C:13]([O:19][CH2:20][CH3:21])(=[O:18])[CH2:14]C([O-])=O.N1CCCCC1.C(=O)=O.Cl>N1C=CC=CC=1>[CH3:1][O:2][C:3]1[CH:10]=[C:9]([O:11][CH3:12])[CH:8]=[CH:7][C:4]=1[CH:5]=[CH:14][C:13]([O:19][CH2:20][CH3:21])=[O:18]
Reactant: COc1ccc(C=O)c(OC)c1
Reactant: CCOC(=O)CC(=O)[O-]
Agent: Cl
Agent: O=C=O
Solvent: c1ccncc1
Solvent: C1CCNCC1
Product: CCOC(=O)C=Cc1ccc(OC)cc1OC
Reaction time: 0.33 h

Procedure:
83 g of 2,4-dimethoxybenzaldehyde and 66 g of monoethyl malonate are dissolved in 100 ml of dry pyridine and, after addition of 1 ml of piperidine and 40 g of molecular sieves, refluxed until evolution of CO2 has ceased. The reaction mixture is cooled and then poured onto crushed ice, and the pH is adjusted to 1-2 with concentrated hydrochloric acid, while stirring. Stirring is continued for 20 minutes, and the product which has separated out is filtered off with suction, washed with 1 N hydrochloric acid and water and dried in a desiccator. Yield: 100.2 g, melting point 58° C.
Reaction SMILES: [C:1]1([Li])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[OH:8][C:9]1[C:22]2[C:21](=[O:23])[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][C:19]=3[OH:24])[C:14](=[O:25])[C:13]=2[CH:12]=[CH:11][CH:10]=1>O1CCCC1>[OH:8][C:9]1[C:22]2[C:21](=[O:23])[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][C:19]=3[OH:24])[C:14]([OH:25])([C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)[C:13]=2[CH:12]=[CH:11][CH:10]=1
Reactant: O=C1c2cccc(O)c2C(=O)c2c(O)cccc21
Reactant: [Li]c1ccccc1
Solvent: C1CCOC1
Product: O=C1c2c(O)cccc2C(O)(c2ccccc2)c2cccc(O)c21

Procedure:
The process of the present invention comprises reacting phenyl lithium with 1,8-dihydroxy anthraquinone in the presence of an anhydrous organic solvent, such as tetrahydrofuran, to form 1,8,10-trihydroxy-10-phenyl-9-anthrone which is then reduced with a reducing agent so as to produce 1,8-dihydroxy-10-phenyl-9-anthrone.
Reaction SMILES: Br[C:2]1[CH:17]=[CH:16][C:5]([O:6][CH2:7][CH2:8][N:9]2[CH2:14][CH2:13][N:12]([CH3:15])[CH2:11][CH2:10]2)=[CH:4][C:3]=1[Cl:18].[Li]CCCC.[B:24](OC(C)C)([O:29][CH:30]([CH3:32])[CH3:31])[O:25][CH:26]([CH3:28])[CH3:27]>>[Cl:18][C:3]1[CH:4]=[C:5]([O:6][CH2:7][CH2:8][N:9]2[CH2:14][CH2:13][N:12]([CH3:15])[CH2:11][CH2:10]2)[CH:16]=[CH:17][C:2]=1[B:24]([O:29][CH:30]([CH3:32])[CH3:31])[O:25][CH:26]([CH3:28])[CH3:27]
Reactant: CN1CCN(CCOc2ccc(Br)c(Cl)c2)CC1
Reactant: CC(C)OB(OC(C)C)OC(C)C
Agent: [Li]CCCC
Product: CC(C)OB(OC(C)C)c1ccc(OCCN2CCN(C)CC2)cc1Cl

Procedure:
1-[2-(4-Bromo-3-chlorophenoxy)ethyl]-4-methyl-piperazine was reacted with n-BuLi at 0° C. in the presence of triisopropyl borate to give diisopropyl 2-chloro-4-(2-(4-methylpiperazin-1-yl)ethoxy)phenylboronate upon warming to room temperature.
Reaction SMILES: [C:1](=[O:4])([OH:3])[O-:2].[Mg+2].[C:6](=[O:9])([OH:8])[O-:7].[Nd:10]>C([O-])(=O)C.[Nd+3].C([O-])(=O)C.C([O-])(=O)C>[C:1](=[O:2])([O-:4])[O-:3].[Nd+3:10].[C:6](=[O:7])([O-:9])[O-:8].[C:1](=[O:2])([O-:4])[O-:3].[Nd+3:10]
Reactant: [Nd]
Reactant: O=C([O-])O
Agent: CC(=O)[O-]
Agent: [Mg+2]
Agent: [Nd+3]
Product: O=C([O-])[O-]

Procedure:
Adding 9 m3 of magnesium bicarbonate solution (MgO: 15 g/L, Fe: 1.1 ppm, Al: 0.5 ppm, saturated with CO2) into a reactor containing 10 m3 of neodymium acetate solution (0.2 mol/L) to react for 2 hours at 25° C., and controlling the pH value of mother liquor at 5.5, neodymium ions are precipitated and neodymium carbonate is obtained. Subsequently, the neodymium carbonate is filtered, washed, dried and finally calcined at 700° C. for 2 hours to produce neodymium oxide.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[C:10]([C:20]([OH:22])=O)[CH:11]=[N:12][C:13]=2[O:14][CH2:15][C:16]([F:19])([F:18])[F:17])=[CH:4][CH:3]=1.FC(F)(F)C(O)=O.C([Si](C)(C)[O:35][CH2:36][CH2:37][CH:38]1[CH2:43][CH2:42][N:41]([NH2:44])[CH2:40][CH2:39]1)(C)(C)C>>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[C:10]([C:20]([NH:44][N:41]3[CH2:42][CH2:43][CH:38]([CH2:37][CH2:36][OH:35])[CH2:39][CH2:40]3)=[O:22])[CH:11]=[N:12][C:13]=2[O:14][CH2:15][C:16]([F:19])([F:18])[F:17])=[CH:4][CH:3]=1
Reactant: O=C(O)c1cnc(OCC(F)(F)F)c(-c2ccc(Cl)cc2)c1
Reactant: CC(C)(C)[Si](C)(C)OCCC1CCN(N)CC1
Solvent: O=C(O)C(F)(F)F
Product: O=C(NN1CCC(CCO)CC1)c1cnc(OCC(F)(F)F)c(-c2ccc(Cl)cc2)c1

Procedure:
The title compound was synthesized in analogy to Example 1 using 5-(4-chlorophenyl)-6-(2,2,2-trifluoroethoxy)-3-pyridinecarboxylic acid (CAN 1018782-82-5) and 4-[2-(t-butyl-dimethyl-silanyloxy)-ethyl]-piperidin-1-ylamine trifluoroacetate (1:1) as starting materials; the silyl protecting group was lost during reaction and work-up; LC-MS (UV peak area/ESI) 94.9%, 458.1448 (M+H)+.
Reaction SMILES: [C:1]1([N:7]2[C:12](=O)C3SC=C(C4C=CC=CC=4)C=3N=C2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[NH2:23][C:24]1[C:28]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=2[Cl:35])=[CH:27][S:26][C:25]=1[C:36]([O:38]C)=O.C(OCC)(OCC)OCC.[Cl:50]C1C=CC(N)=CC=1>C(O)(=O)C>[Cl:35][C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][C:29]=1[C:28]1[C:24]2[N:23]=[CH:12][N:7]([C:1]3[CH:6]=[CH:5][C:4]([Cl:50])=[CH:3][CH:2]=3)[C:36](=[O:38])[C:25]=2[S:26][CH:27]=1
Reactant: O=c1c2scc(-c3ccccc3)c2ncn1-c1ccccc1
Reactant: Nc1ccc(Cl)cc1
Reactant: COC(=O)c1scc(-c2ccccc2Cl)c1N
Solvent: CC(=O)O
Solvent: CCOC(OCC)OCC
Product: O=c1c2scc(-c3ccccc3Cl)c2ncn1-c1ccc(Cl)cc1
Yield: 23 %

Procedure:
In the same manner as the synthesis of Compound 1, methyl 3-amino-4-(2-chlorophenyl)thiophene-2-carboxylate (100 mg, 0.373 mmol), triethyl orthoformate (2 ml), 4-chloroaniline (88.5 mg, 0.70 mmol), and acetic acid (0.1 ml) were used to give 31.3 mg (0.084 mmol, 23% yield) of the title compound.
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].[CH:7]([S:11]([NH:14][C:15](=[O:25])[C:16]1[CH:21]=[C:20]([F:22])[C:19](F)=[CH:18][C:17]=1[F:24])(=[O:13])=[O:12])([CH2:9][CH3:10])[CH3:8].[Cl:26][C:27]1[CH:28]=[C:29]([OH:35])[CH:30]=[N:31][C:32]=1[O:33][CH3:34]>CS(C)=O.O>[CH:7]([S:11]([NH:14][C:15](=[O:25])[C:16]1[CH:21]=[C:20]([F:22])[C:19]([O:35][C:29]2[CH:30]=[N:31][C:32]([O:33][CH3:34])=[C:27]([Cl:26])[CH:28]=2)=[CH:18][C:17]=1[F:24])(=[O:13])=[O:12])([CH2:9][CH3:10])[CH3:8]
Reactant: COc1ncc(O)cc1Cl
Reactant: CCC(C)S(=O)(=O)NC(=O)c1cc(F)c(F)cc1F
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CS(C)=O
Product: CCC(C)S(=O)(=O)NC(=O)c1cc(F)c(Oc2cnc(OC)c(Cl)c2)cc1F
Temperature: 90 °C
Yield: 52.1 %

Procedure:
Potassium carbonate (0.140 g, 1.01 mmol) was added to a stirred solution of N-(sec-butylsulfonyl)-2,4,5-trifluorobenzamide (Preparation 68, 0.090 g, 0.30 mmol) in DMSO (1 mL). After 10 minutes a solution of 5-chloro-6-methoxypyridin-3-ol (Preparation 77, 0.088 g, 0.51 mmol) in DMSO (2 mL) was added at room temperature. The mixture was heated at 90° C. for 72 hours. The reaction mixture was diluted with water (25 mL) and extracted with EtOAc (3×25 mL). The combined organics were washed with water (25 mL), dried over magnesium sulfate, filtered, evaporated in vacuo. The resulting crude product was purified by silica gel chromatography eluting with 0 to 66% EtOAc in heptane to yield the title compound (0.068 g):
Reaction SMILES: [CH2:1]([Zn]CC)C.[CH:6]([O:8][CH2:9][CH2:10][CH2:11][C:12]([CH3:35])=[CH:13][CH2:14][CH2:15][C:16]([CH3:34])=[CH:17][CH2:18][CH2:19][CH:20]=[C:21]([CH3:33])[CH2:22][CH2:23][CH:24]=[C:25]([CH3:32])[CH2:26][CH2:27][CH:28]=[C:29]([CH3:31])[CH3:30])=[CH2:7].ICI>CCOCC>[CH:6]1([O:8][CH2:9][CH2:10][CH2:11][C:12]([CH3:35])=[CH:13][CH2:14][CH2:15][C:16]([CH3:34])=[CH:17][CH2:18][CH2:19][CH:20]=[C:21]([CH3:33])[CH2:22][CH2:23][CH:24]=[C:25]([CH3:32])[CH2:26][CH2:27][CH:28]=[C:29]([CH3:31])[CH3:30])[CH2:1][CH2:7]1
Reactant: C=COCCCC(C)=CCCC(C)=CCCC=C(C)CCC=C(C)CCC=C(C)C
Reactant: CC[Zn]CC
Solvent: ICI
Solvent: CCOCC
Product: CC(C)=CCCC(C)=CCCC(C)=CCCC=C(C)CCC=C(C)CCCOC1CC1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
Diethyl zinc (0.606 ml, 1.0 M in hexane) was added to 4,8,13,17,21-pentamethyl-4,8,12,16,20-docosapentaen-1-ol vinyl ether (0.250 g, 0.606 mmol) in 6 ml ether under argon. Diiodomethane (0.240 g, 0.606 mmol, 73.3 μl), in 2 ml ether, was added dropwise over 0.5 hour. After stirring overnight at room temperature, the reaction was quenched with saturated ammonium chloride. An additional 40 ml of ether and 20 ml of saturated ammonium chloride were added and the layers separated. The ether layer was washed with brine and dried over magnesium sulfate. Removal of the solvent in vacuo yielded 0.32 g of crude product, which wasshown to be a 3:1 mixture by capillary gas chromatography of 4,8,13,17,21-pentamethyl-4,8,12,16,20-docosapentane-1-ol cyclopropyl etherand a dicyclopropyl compound.