Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[C:2]1[CH:3]=[C:4]([C:8]#[C:9][C:10]2[CH2:14][C:13]3([CH2:19][CH2:18][C:17](=[O:20])[CH2:16][CH2:15]3)[O:12][N:11]=2)[CH:5]=[CH:6][CH:7]=1.C1(C#CC2CC3(CCC4(OCCO4)CC3)ON=2)C=CC=CC=1>>[C:4]1([C:8]#[C:9][C:10]2[CH2:14][C:13]3([CH2:19][CH2:18][C:17](=[O:20])[CH2:16][CH2:15]3)[O:12][N:11]=2)[CH:5]=[CH:6][CH:7]=[CH:2][CH:3]=1
Reactant: O=C1CCC2(CC1)CC(C#Cc1cccc(Cl)c1)=NO2
Agent: C(#Cc1ccccc1)C1=NOC2(CCC3(CC2)OCCO3)C1
Product: O=C1CCC2(CC1)CC(C#Cc1ccccc1)=NO2

Procedure:
The title compound was synthesized using the same method described for the compound of Example 32, but starting from the compound of Example 44 instead of the compound of Example 31. The crude was purified by automated flash chromatography (SP1®TM-Biotage; Petroleum Ether-EtOAc 8:2) to give the title product as white solid. Yield: 80%.
Reaction SMILES: [CH3:1][C:2]1[NH:3][CH:4]=[CH:5][C:6]=1[C:7]([O:9][CH2:10][CH3:11])=[O:8].[Br:12]N1C(=O)CCC1=O.O.C(OCC)C>O1CCCC1>[Br:12][C:4]1[NH:3][C:2]([CH3:1])=[C:6]([C:7]([O:9][CH2:10][CH3:11])=[O:8])[CH:5]=1
Reactant: CCOC(=O)c1cc[nH]c1C
Reactant: O=C1CCC(=O)N1Br
Solvent: CCOCC
Solvent: C1CCOC1
Solvent: O
Product: CCOC(=O)c1cc(Br)[nH]c1C
Reaction time: 0.5 h
Yield: 97.5 %

Procedure:
To a solution of ethyl 2-methyl-1H-pyrrole-3-carboxylate (1.53 g) in tetrahydrofuran (20 mL) was added N-bromosuccinimide (1.78 g) at −78° C., and the mixture was stirred at the same temperature for 30 min. Water and diethyl ether were added to extract the reaction mixture. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure at 5° C. or below. The residue was washed with hexane to give the title compound as a colorless solid (yield 2.26 g, 97%).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][N:5]2[CH:8]=[CH:9][N:10]=[C:4]2[CH:3]=1.[I:11]N1C(=O)CCC1=O>CN(C=O)C.O.[Cl-].[Na+].O>[Cl:1][C:2]1[CH:7]=[CH:6][N:5]2[C:8]([I:11])=[CH:9][N:10]=[C:4]2[CH:3]=1
Reactant: O=C1CCC(=O)N1I
Reactant: Clc1ccn2ccnc2c1
Agent: [Cl-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: Clc1ccn2c(I)cnc2c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 75.3 %

Procedure:
To a solution of 7-Chloro-imidazo[1,2-a]pyridine (30.9 g, 186 mmol, 1.0 equiv) in DMF (280 ml) was added N-iodosuccinimide (43.6 g, 194 mmol, 1.05 equiv) and the resulting mixture was stirred overnight at RT. The thin brown slurry was diluted with water (840 ml), brine (280 ml) and extracted with EtOAc (560 ml). The aqueous was further extracted with EtOAc (3×280 ml). The combined organic phases were washed with water (2×280 ml), 10% w/v sodium thiosulfate (280 ml), brine (280 ml), dried (MgSO4), filtered and concentrated in vacuo to give a brown residue. The residue was triturated with ether (200 ml), filtered and the solid was washed ether (2×50 ml) and dried on the filter to give 39 g of product. MS: [M+H]+ 279
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([C:8]([C:10]2[S:11][C:12]([CH3:16])=[C:13]([CH3:15])[N:14]=2)=O)[O:5][C:6]=1[CH3:7].[NH3:17]>CO>[CH3:1][C:2]1[CH:3]=[C:4]([OH:5])[C:8]([C:10]2[S:11][C:12]([CH3:16])=[C:13]([CH3:15])[N:14]=2)=[N:17][C:6]=1[CH3:7]
Reactant: Cc1cc(C(=O)c2nc(C)c(C)s2)oc1C
Reactant: N
Solvent: CO
Product: Cc1cc(O)c(-c2nc(C)c(C)s2)nc1C
Temperature: 160 °C
Reaction time: 8 h
Yield: 86 %

Procedure:
(4,5-Dimethylfuran-2-yl)-(4,5-dimethylthiazol-2-yl)methanone (910 mg), methanol (7 ml), and 8 ml of a 28% aqueous ammonia solution were placed in a sealed tube, and the mixture was stirred at 160° C. overnight. The reaction solution was cooled to room temperature, the solvent was then removed by distillation under the reduced pressure, and the residue was purified by column chromatography using hexane-ethyl acetate to give 5,6-dimethyl-2-(4,5-dimethylthiazol-2-yl)pyridin-3-ol (782 mg, yield 86%).
Reaction SMILES: [C:1]([O:5][C:6](=[O:22])[NH:7][C:8]([CH3:21])([CH3:20])[CH2:9][C:10]1[C:18]2[C:13](=[C:14]([OH:19])[CH:15]=[CH:16][CH:17]=2)[NH:12][CH:11]=1)([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].Cl[C:26]1[N:33]=[CH:32][CH:31]=[CH:30][C:27]=1[C:28]#[N:29].O>CN(C)C=O>[C:1]([O:5][C:6](=[O:22])[NH:7][C:8]([CH3:21])([CH3:20])[CH2:9][C:10]1[C:18]2[C:13](=[C:14]([O:19][C:26]3[C:27]([C:28]#[N:29])=[CH:30][CH:31]=[CH:32][N:33]=3)[CH:15]=[CH:16][CH:17]=2)[NH:12][CH:11]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(Cc1c[nH]c2c(O)cccc12)NC(=O)OC(C)(C)C
Reactant: N#Cc1cccnc1Cl
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: CC(C)(Cc1c[nH]c2c(Oc3ncccc3C#N)cccc12)NC(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 0.42 h
Yield: 95.7 %

Procedure:
To a solution of [2-(7-Hydroxy-1H-indol-3-yl)-1,1-dimethyl-ethyl]-carbamic acid tert-butyl ester (274 mg, 0.900 mmol) in dimethylformamide (15 mL) is added sodium hydride (26 mg, 1.07 mmol). The mixture is stirred at ambient temperature for 25 minutes under nitrogen. 2-Chloro-nicotinonitrile (187 mg, 1.35 mmol) is added and the mixture is heated in an oil bath to eighty degrees Celsius for 15 hours, under nitrogen. Water (50 ml) is added to quench the reaction and the mixture is extracted three times with 50 mL of ethyl acetate. The organic layers are combined and washed twice with 50 mL of 1.00 N sodium hydroxide. The organic layer is dried with sodium sulfate, filtered and the solvent evaporated. The residue is dissolved in dichloromethane and purified using silica gel chromatography (6% 2M ammonia in methanol, 94% dichloromethane used as mobile phase) to give 350 mg (96%) of {2-[7-(3-cyano-pyridin-2-yloxy)-1H-indol-3-yl]-1,1-dimethyl-ethyl}-carbamic acid tert-butyl ester. FDMS m/e=407 (M++1).
Reaction SMILES: Cl.[CH3:2][C:3]1([CH3:9])[O:8][CH2:7][CH2:6][NH:5][CH2:4]1.[OH-].[Na+].[O:12]1[C@H:14]2[CH2:15][C@H:16]3[C@:29]([CH3:31])([CH2:30][C@@H:13]12)[C@@H:28]1[C@H:19]([C@H:20]2[C@@:24]([CH2:26][CH2:27]1)([CH3:25])[C@@H:23]([C:32]#[N:33])[CH2:22][CH2:21]2)[CH2:18][CH2:17]3.O>C(O)CO>[OH:12][C@@H:14]1[C@@H:13]([N:5]2[CH2:6][CH2:7][O:8][C:3]([CH3:9])([CH3:2])[CH2:4]2)[CH2:30][C@@:29]2([CH3:31])[C@@H:16]([CH2:17][CH2:18][C@@H:19]3[C@@H:28]2[CH2:27][CH2:26][C@@:24]2([CH3:25])[C@H:20]3[CH2:21][CH2:22][C@@H:23]2[C:32]#[N:33])[CH2:15]1
Reactant: C[C@]12C[C@H]3O[C@H]3C[C@@H]1CC[C@@H]1[C@@H]2CC[C@]2(C)[C@@H](C#N)CC[C@@H]12
Reactant: CC1(C)CNCCO1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: OCCO
Product: CC1(C)CN([C@H]2C[C@@]3(C)[C@@H](CC[C@@H]4[C@@H]3CC[C@]3(C)[C@@H](C#N)CC[C@@H]43)C[C@@H]2O)CCO1
Temperature: 135 °C
Yield: 54.3 %

Procedure:
2,2-Dimethylmorpholine hydrochloride (2.43 g) and sodium hydroxide (640 mg) were added to a mixture of (2α,3α,5α,17β)-2,3-epoxyandrostane-17-carbonitrile (1.2 g) (prepared as described in British patent 1,434,919) in 1,2-ethanediol (12 ml) and the mixture was heated at 135° C. in an atmosphere of nitrogen for 24 h. The reaction mixture was poured into water (100 ml) and the precipitated solid was filtered off and then dissolved in dichloromethane. The solution was washed with water and dried over sodium sulfate. The solvent was removed under reduced pressure and the residue (1.55 g) was chromatographed on silica gel. The purified product (1.18 g) was crystallised from ether-heptane to give (2β,3α,5α,17β)-3-hydroxy-2-(2,2-dimethyl-4-morpholinyl)androstane-17-carbonitrile (903 mg). m.p. 170°-173° C.; [α]D +117.5° (c 0.8).
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:18])[CH2:5][C:6]1[C:14]2[C:9](=[CH:10][CH:11]=[C:12]([O:15][CH3:16])[CH:13]=2)[NH:8][C:7]=1[CH3:17])[CH3:2].[H-].[Na+].Br[CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=1[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1>O>[CH2:1]([O:3][C:4](=[O:18])[CH2:5][C:6]1[C:14]2[C:9](=[CH:10][CH:11]=[C:12]([O:15][CH3:16])[CH:13]=2)[N:8]([CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=2[C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[C:7]=1[CH3:17])[CH3:2]
Reactant: CCOC(=O)Cc1c(C)[nH]c2ccc(OC)cc12
Reactant: BrCc1ccccc1-c1ccccc1
Agent: [H-]
Agent: [Na+]
Solvent: O
Product: CCOC(=O)Cc1c(C)n(Cc2ccccc2-c2ccccc2)c2ccc(OC)cc12
Reaction time: 0.5 h
Yield: 72 %

Procedure:
1-([1,11′-Biphenyl]-2-ylmethyl)-5-methoxy,y-2-methyl-1H-indole-3-acetic acid ethyl ester. 5-Methoxy-2-methyl-1H-indole-3-acetic acid ethyl ester (988 mg, 4 mmol) was added to 160 mg (4 mmol) of NaH/mineral oil (previously washed with hexane), the mixture stirred for 0.5 hours and 0.74 mL (4 mmol) of2- (bromomethyl) biphenyl added. After 2 hours, water was added and the mixture extracted with ethyl acetate. The ethyl acetate was washed with brine, dried (MgSO4) and concentrated at reduced pressure. The residue was chromatographed on silica gel eluting with 20% EtOAc/hexane to give 1.18 g (72% yield) of 1-([1,1′-biphenyl]-2-ylmethyl)-5-methoxy-2-methyl-1H-indole-3-acetic acid ethyl ester as an oil.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[N:4][N:5]([CH2:7][C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([O:14]C)[CH:9]=2)[CH:6]=1.B(Br)(Br)Br>C(Cl)Cl>[Br:1][C:2]1[CH:3]=[N:4][N:5]([CH2:7][C:8]2[CH:9]=[C:10]([OH:14])[CH:11]=[CH:12][CH:13]=2)[CH:6]=1
Reactant: COc1cccc(Cn2cc(Br)cn2)c1
Agent: BrB(Br)Br
Solvent: ClCCl
Product: Oc1cccc(Cn2cc(Br)cn2)c1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 70.8 %

Procedure:
To a solution of 4-bromo-1-(3-methoxybenzyl)-1H-pyrazole (3.8 g, 14.23 mmol) was dissolved in CH2Cl2 (30 mL) at 0° C. was added boron tribromide (2.69 mL, 28.5 mmol). The reaction mixture was stirred at 0° C. for 30 min and concentrated. The resulting residue was purified by flash chromatography (0-100% ethyl acetate:hexanes) to afford the title compound (2.55 g, 71% yield) as a yellow oil. LCMS, [M+H]+=253.0. 1H NMR (400 MHz, CDCl3) δ 7.47 (s, 1H), 7.38 (s, 1H), 7.19 (t, J=8.0 Hz, 1H), 6.76 (d, J=8.0 Hz, 2H), 6.59 (s, 1H), 5.20 (s, 2H).
Reaction SMILES: NN.[CH3:3][O:4][C:5]1[C:27]([O:28][CH3:29])=[CH:26][C:8]([C:9]([N:11]2[CH2:15][C@H:14]([OH:16])[CH2:13][CH:12]2[CH2:17][O:18][Si:19]([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:21])[CH3:20])=[O:10])=[C:7]([N+:30]([O-])=O)[CH:6]=1.O=[Al]O[Al]=O.C(Cl)(Cl)Cl.CO>CO.[Ni]>[NH2:30][C:7]1[CH:6]=[C:5]([O:4][CH3:3])[C:27]([O:28][CH3:29])=[CH:26][C:8]=1[C:9]([N:11]1[CH2:15][C@H:14]([OH:16])[CH2:13][C@H:12]1[CH2:17][O:18][Si:19]([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:21])[CH3:20])=[O:10]
Reactant: COc1cc(C(=O)N2C[C@H](O)CC2CO[Si](C)(C)C(C)(C)C)c([N+](=O)[O-])cc1OC
Agent: [Ni]
Agent: NN
Agent: O=[Al]O[Al]=O
Solvent: CO
Solvent: ClC(Cl)Cl
Product: COc1cc(N)c(C(=O)N2C[C@H](O)C[C@H]2CO[Si](C)(C)C(C)(C)C)cc1OC
Temperature: 25 °C
Yield: 95 %

Procedure:
A solution of hydrazine (6.59 g, 6.40 mL, 205.5 mmol) in MeOH (110 mL) was added dropwise to a solution of the nitro-compound 35 (18.1 g, 41.1 mmol), over anti-bumping granules and Raney Ni (2.6 g) in MeOH (325 mL) and heated at reflux. After 1 hour at reflux TLC (95% CHCl3/MeOH) revealed some amine formation. The reaction mixture was treated with further Raney Ni (2.6 g) and hydrazine (6.40 mL) in MeOH (50 mL) and was heated at reflux for an additional 30 minutes at which point TLC revealed reaction completion. The reaction mixture was then treated with sufficient Raney Ni to decompose any remaining hydrazine and heated at reflux for a further 1.5 h. Following cooling to room temperature the mixture was filtered through a sinter and the resulting filtrate evaporated in vacuo. The resulting residue was then treated with CH2Cl2 (300 mL), dried (MgSO4), filtered and evaporated in vacuo to provide the amine 36 as a green oil (16.03 g, 95%): [α]22D=−116.32 (c=0.31, CHCl3); 1H NMR (270 MHz, CDCl3) (Rotamers) δ 6.70 (s, 1H), 6.28 (s, 1H), 4.51-4.49 (m, 1H), 4.36-4.34 (m, 1H), 4.06-3.77 (m, 10H), 3.61-3.50 (m, 3H), 2.23-2.21 (m, 1H), 2.01-1.98 (m, 1H), 0.89 (s, 9H), 0.04 (s, 6H); 13C NMR (67.8 MHz, CDCl3) (Rotamers) δ 170.2, 151.5, 141.2, 140.5, 112.2, 112.0, 101.1, 70.4, 62.6, 59.0, 56.9, 56.6, 55.8, 35.7, 25.9 and 25.7, 18.2, −5.4 and −5.5; MS (EI), m/z (relative intensity) 412 (M+.+2, 3), 411 (M+.+1, 10), 410 (M+., 32), 354 (6), 353 (23), 263 (3), 212 (5), 181 (11), 180 (100), 179 (3), 165 (3), 164 (6), 152 (10), 137 (4), 136 (4), 125 (5), 120 (3), 100 (3), 94 (6), 75 (9), 73 (7), 57 (3); IR (CHCl3) 3353 (br), 2953, 2930, 2857, 1623, 1594, 1558, 1517, 1464, 1435, 1404, 1260, 1234, 1215, 1175, 1119, 1060, 1005, 915, 836, 777, 755, 666 cm−1, exact mass calcd for C20H34N2O5Si m/e 410.2237, obsd m/e 410.2281.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[OH:9].Cl[CH2:11][CH:12]([OH:16])[CH2:13][CH2:14][Cl:15].[OH-].[Na+].O>C(O)(C)(C)C>[Cl:15][CH2:14][CH2:13][CH:12]([OH:16])[CH2:11][O:9][C:3]1[CH:4]=[CH:5][C:6]([Cl:8])=[CH:7][C:2]=1[CH3:1]
Reactant: OC(CCl)CCCl
Reactant: Cc1cc(Cl)ccc1O
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CC(C)(C)O
Product: Cc1cc(Cl)ccc1OCC(O)CCCl

Procedure:
4-Chloro-1-(4-chloro-2-methylphenoxy)-2-butanol was prepared according to the procedure of Preparation 4 using 105 g. (0.74 mole) of 2-methyl-4-chlorophenol, 171.5 g. (1.2 mole) of 1,4-dichloro-2-butanol, 50.3 g. of sodium hydroxide, 300 ml. of water and 300 ml. of tertiary butanol. There was obtained 84 g. (45.5%) of product which distilled at 135° C./0.01 mm.
Reaction SMILES: [CH2:1]([O:8][C:9]([NH:11][C@@H:12]([CH:21]([CH3:23])[CH3:22])[CH:13]([OH:20])[CH2:14][C:15]([O:17][CH2:18][CH3:19])=[O:16])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.N1C(C)=CC=CC=1C.[CH3:32][C:33]([Si:36](OS(C(F)(F)F)(=O)=O)([CH3:38])[CH3:37])([CH3:35])[CH3:34]>C1COCC1>[CH2:1]([O:8][C:9]([NH:11][C@@H:12]([CH:21]([CH3:22])[CH3:23])[CH:13]([O:20][Si:36]([C:33]([CH3:35])([CH3:34])[CH3:32])([CH3:38])[CH3:37])[CH2:14][C:15]([O:17][CH2:18][CH3:19])=[O:16])=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CC(C)(C)[Si](C)(C)OS(=O)(=O)C(F)(F)F
Reactant: CCOC(=O)CC(O)[C@@H](NC(=O)OCc1ccccc1)C(C)C
Solvent: Cc1cccc(C)n1
Solvent: C1CCOC1
Product: CCOC(=O)CC(O[Si](C)(C)C(C)(C)C)[C@@H](NC(=O)OCc1ccccc1)C(C)C
Temperature: 25 °C
Yield: 88.7 %

Procedure:
Under an argon atmosphere, to a solution (228 mL) of ethyl (4S)-4-{[(benzyloxy)carbonyl]amino}-3-hydroxy-5-methylhexanoate (14.74 g) in dehydrated THF was added 2,6-lutidine (7.33 g) with stirring under ice-cooling, and tert-butyl dimethylsilyl trifluoromethanesulfonate (14.46 g) was added dropwise. The mixture was gradually warmed to room temperature and stirred for 1.5 hr. The reaction mixture was poured into ice water, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated. The residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate=19/1→4/1) to give ethyl (4S)-4-{[(benzyloxy)carbonyl]amino}-3-{[tert-butyl(dimethyl)silyl]oxy}-5-methylhexanoate as colorless oil (yield: 17.7 g).
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([C:8]#[N:9])[C:5]2[N:10]=[CH:11][N:12]([CH3:13])[C:4]=2[CH:3]=1.[OH:14][CH2:15][CH2:16][CH2:17][O:18][C:19]1[CH:24]=[CH:23][C:22](B(O)O)=[CH:21][C:20]=1[C:28]([F:31])([F:30])[F:29].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O.C(OCC)(=O)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[OH:14][CH2:15][CH2:16][CH2:17][O:18][C:19]1[CH:24]=[CH:23][C:22]([C:2]2[N:7]=[C:6]([C:8]#[N:9])[C:5]3[N:10]=[CH:11][N:12]([CH3:13])[C:4]=3[CH:3]=2)=[CH:21][C:20]=1[C:28]([F:29])([F:30])[F:31]
Reactant: OCCCOc1ccc(B(O)O)cc1C(F)(F)F
Reactant: Cn1cnc2c(C#N)nc(Cl)cc21
Agent: [Pd]
Agent: C1CCC(P(C2CCCCC2)C2CCCCC2)CC1
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Solvent: O
Solvent: C1COCCO1
Solvent: CCOC(C)=O
Product: Cn1cnc2c(C#N)nc(-c3ccc(OCCCO)c(C(F)(F)F)c3)cc21
Temperature: 100 °C

Procedure:
A mixture of 6-chloro-1-methyl-1H-imidazo[4,5-c]pyridine-4-carbonitrile (6 g), 4-(3-hydroxypropoxy)-3-(trifluoromethyl)phenylboronic acid (12.3 g), tris(dibenzylideneacetone)dipalladium (1.42 g), tricyclohexylphosphine (1.05 g) and tribasic potassium phosphate (13.2 g) in dioxane (60 ml) and water (24 ml) was heated at 100° C. under N2 for 4 hours. The mixture was then diluted with ethyl acetate (400 ml), organic layer seperated and solvent removed under reduced pressure, to the residue was then added methanol (50 ml), product crystalised out and collected by filtration (7.7 g). 1H NMR (DMSO) δ: 8.67 (s, 1H), 8.60 (s, 1H), 8.43 (d, 1H), 8.37 (s, 1H), 7.41 (d, 1H), 4.55 (t, 1H), 4.25 (t, 2H), 3.99 (s, 3H), 3.58 (q, 2H), 1.92 (tt, 2H). MS m/z 377 (M+H).
Reaction SMILES: C1(C2C=CC(C(NC3C=C(F)C=C(C4C5C=C(C6CCNCC=6)NC=5N=CN=4)C=3C)=O)=CC=2)CC1.C(OC([N:43]1[CH2:48][CH:47]=[C:46]([C:49]2[NH:80][C:52]3[N:53]=[CH:54][N:55]=[C:56]([C:57]4[CH:62]=[C:61]([F:63])[CH:60]=[C:59]([NH:64][C:65](=[O:78])[C:66]5[CH:71]=[CH:70][C:69]([S:72]([F:77])([F:76])([F:75])([F:74])[F:73])=[CH:68][CH:67]=5)[C:58]=4[CH3:79])[C:51]=3[CH:50]=2)[CH2:45][CH2:44]1)=O)(C)(C)C>>[F:63][C:61]1[CH:62]=[C:57]([C:56]2[C:51]3[CH:50]=[C:49]([C:46]4[CH2:47][CH2:48][NH:43][CH2:44][CH:45]=4)[NH:80][C:52]=3[N:53]=[CH:54][N:55]=2)[C:58]([CH3:79])=[C:59]([NH:64][C:65](=[O:78])[C:66]2[CH:71]=[CH:70][C:69]([S:72]([F:77])([F:73])([F:74])([F:75])[F:76])=[CH:68][CH:67]=2)[CH:60]=1
Reactant: Cc1c(NC(=O)c2ccc(S(F)(F)(F)(F)F)cc2)cc(F)cc1-c1ncnc2[nH]c(C3=CCN(C(=O)OC(C)(C)C)CC3)cc12
Agent: Cc1c(NC(=O)c2ccc(C3CC3)cc2)cc(F)cc1-c1ncnc2[nH]c(C3=CCNCC3)cc12
Product: Cc1c(NC(=O)c2ccc(S(F)(F)(F)(F)F)cc2)cc(F)cc1-c1ncnc2[nH]c(C3=CCNCC3)cc12

Procedure:
Intermediate 24 was prepared analogue to Intermediate 22 by replacing Intermediate 21 with Intermediate 23.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[NH:13][NH:12][C:11](=[O:14])[CH2:10][CH:9]2[CH3:15])=[CH:4][CH:3]=1.Cl[C:17]([O:19][CH3:20])=[O:18]>C1(C)C=CC=CC=1>[CH3:20][O:19][C:17]([NH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]([CH3:15])[CH2:10][C:11](=[O:14])[NH:12][N:13]=2)=[CH:4][CH:3]=1)=[O:18]
Reactant: COC(=O)Cl
Reactant: CC1CC(=O)NNC1c1ccc(N)cc1
Solvent: Cc1ccccc1
Product: COC(=O)Nc1ccc(C2=NNC(=O)CC2C)cc1
Yield: 40.2 %

Procedure:
6.0 g (29.5 millimoles) of 6-(p-aminophenyl)-4,5-dihydro-dihydro-5-methyl-3(2H)-pyridazinone and 3.3 g (34.9 millimoles) of methyl chloroformate in 100 ml of absolute toluene are kept for 6 hours at 80° C. The product is filtered off at 10° C., washed first with toluene and then with water, and recrystallized from dimethylformamide/water. 3.1 g (40% of theory) of 4,5-dihydro-6-(p-methoxycarbonylaminophenyl)-5-methyl-3(2H)-pyridazinone are obtained as colorless crystals, of melting point 228°-229° C.
Reaction SMILES: [NH2:1][C:2]1[C:10]2[C:5](=[CH:6][C:7]([Cl:11])=[CH:8][CH:9]=2)[NH:4][C:3]=1[C:12]([C:14]1[CH:18]=[CH:17][O:16][CH:15]=1)=[O:13].[C:19](Cl)(=[O:21])[CH3:20]>C(OCC)(=O)C.CCCCCC>[C:19]([NH:1][C:2]1[C:10]2[C:5](=[CH:6][C:7]([Cl:11])=[CH:8][CH:9]=2)[NH:4][C:3]=1[C:12]([C:14]1[CH:18]=[CH:17][O:16][CH:15]=1)=[O:13])(=[O:21])[CH3:20]
Reactant: CC(=O)Cl
Reactant: Nc1c(C(=O)c2ccoc2)[nH]c2cc(Cl)ccc12
Solvent: CCOC(C)=O
Solvent: CCCCCC
Product: CC(=O)Nc1c(C(=O)c2ccoc2)[nH]c2cc(Cl)ccc12

Procedure:
The title compound was prepared according to the procedure described in Example 19 from 3-amino-6-chloro-2-(3-furoyl)indole (Example 79) and acetyl chloride. m.p.:217-219° C. (ethyl acetate/hexane)
Reaction SMILES: Cl.[Cl:2][C:3]1[CH:19]=[CH:18][C:6]([CH2:7][N:8]([C:10]2[CH:15]=[C:14]([Cl:16])[CH:13]=[C:12]([Cl:17])[CH:11]=2)N)=[CH:5][CH:4]=1.[CH3:20][CH2:21][O:22][C:23]([CH2:25][CH:26]1[C:31](=O)[CH2:30][CH2:29][CH2:28][CH2:27]1)=[O:24]>>[Cl:2][C:3]1[CH:19]=[CH:18][C:6]([CH2:7][N:8]2[C:27]3[CH:26]([CH2:25][C:23]([O:22][CH2:21][CH3:20])=[O:24])[CH2:31][CH2:30][CH2:29][C:28]=3[C:15]3[C:10]2=[CH:11][C:12]([Cl:17])=[CH:13][C:14]=3[Cl:16])=[CH:5][CH:4]=1
Reactant: CCOC(=O)CC1CCCCC1=O
Reactant: NN(Cc1ccc(Cl)cc1)c1cc(Cl)cc(Cl)c1
Agent: Cl
Product: CCOC(=O)CC1CCCc2c1n(Cc1ccc(Cl)cc1)c1cc(Cl)cc(Cl)c21

Procedure:
Following the procedure of Example 1, but using 1-(4-chlorobenzyl)-1-(3,5-dichlorophenyl)hydrazine hydrochloride and ethyl 2-cyclohexanone acetate as starting materials, the title compound is prepared.
Reaction SMILES: [CH2:1]([O:8][CH2:9][CH2:10][OH:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1(C)C=CC(S(Cl)(=O)=O)=CC=1.[OH-].[Na+].[CH2:25]([O:32][C:33]1[CH:38]=[CH:37][C:36](O)=[CH:35][CH:34]=1)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1>C(#N)C>[CH2:1]([O:8][CH2:9][CH2:10][O:11][C:36]1[CH:37]=[CH:38][C:33]([O:32][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[CH:34][CH:35]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: Oc1ccc(OCc2ccccc2)cc1
Reactant: OCCOCc1ccccc1
Agent: Cc1ccc(S(=O)(=O)Cl)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: CC#N
Product: c1ccc(COCCOc2ccc(OCc3ccccc3)cc2)cc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
2-(Benzyloxy)ethanol (61.0 g, 0.4 mole, and p-toluenesulfonyl chloride (80.0 g, 0.4 mole) were added with stirring to acetonitrile (20 ml) in a litre, four-necked, round-bottom flask, equipped with a mechanical stirrer, reflux condenser, thermometer and a dropping funnel. Aqueous sodium hydroxide (40.0 g, 1.0 mole/80 ml of water) was added slowly from the dropping funnel while the temperature of the reaction mixture was kept below 55° C. After the addition was complete, the reaction mixture was stirred for one hour as it cooled to room temperature. Then, 4-(benzyloxy)phenol (80.0 g, 0.4 mole) was added and the reaction mixture (OV-1 column, 100° C. for 2 minutes, 25° C./min to 300° C. showed that the reaction was complete.
Reaction SMILES: [C:1]([O:4][C@H:5]1[CH2:24][CH2:23][C@@:22]2([CH3:25])[C@@:7]([Cl:28])([C@H:8]([Cl:27])[CH2:9][C@@H:10]3[C@@H:21]2[CH2:20][CH2:19][C@@:18]2([CH3:26])[C@H:11]3[CH2:12][CH2:13][C@@H:14]2[C:15](=[O:17])[CH3:16])[CH2:6]1)(=[O:3])[CH3:2].[F:29]C(F)(F)C([O-])=O.[Na+].[F-].[Na+].FF>FC(Cl)(Cl)Cl.C(Cl)(Cl)Cl>[C:1]([O:4][C@H:5]1[CH2:24][CH2:23][C@@:22]2([CH3:25])[C@@:7]([Cl:28])([C@H:8]([Cl:27])[CH2:9][C@@H:10]3[C@@H:21]2[CH2:20][CH2:19][C@@:18]2([CH3:26])[C@@:11]3([F:29])[CH2:12][CH2:13][C@@H:14]2[C:15](=[O:17])[CH3:16])[CH2:6]1)(=[O:3])[CH3:2]
Reactant: O=C([O-])C(F)(F)F
Reactant: CC(=O)O[C@H]1CC[C@]2(C)[C@H]3CC[C@]4(C)[C@@H](C(C)=O)CC[C@H]4[C@@H]3C[C@@H](Cl)[C@@]2(Cl)C1
Agent: FF
Agent: [F-]
Agent: [Na+]
Solvent: ClC(Cl)Cl
Solvent: FC(Cl)(Cl)Cl
Product: CC(=O)O[C@H]1CC[C@]2(C)[C@H]3CC[C@]4(C)[C@@H](C(C)=O)CC[C@@]4(F)[C@@H]3C[C@@H](Cl)[C@@]2(Cl)C1

Procedure:
3β-Acetoxy-5α,6β-dichloropregnan-20-one (1.4 g) was dissolved in fluorotrichloromethane (250 ml) and chloroform (200 ml) containing sodium trifluoroacetate (ca. 2 g) and sodium fluoride (ca. 2 g). The resulting solution was cooled to -78° and vigourously stirred, whereupon fluorine from four 750 cc bottles (10% v/v fluorine in nitrogen) was bubbled through the solution over a period of 8 hours. The reaction solution was then poured into aqueous sodium thiosulphate and the organic layer was separated, washed with water, dried over potassium carbonate and evaporated to dryness to yield crude 3β-acetoxy-5α,6β-dichloro-14α-fluoropregnan-20-one.