Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([C:3]1[CH:28]=[CH:27][C:6]([C:7]([CH:9]([CH:13]2[C:26]3C=CC=C[C:21]=3[O:20][C:19]3[C:14]2=[CH:15][CH:16]=[CH:17][CH:18]=3)C([O-])=O)=[O:8])=[CH:5][CH:4]=1)#[N:2]>CS(C)=O.O>[O:20]1[C:19]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[CH:13]([CH2:9][C:7]([C:6]2[CH:27]=[CH:28][C:3]([C:1]#[N:2])=[CH:4][CH:5]=2)=[O:8])[CH:26]=[CH:21]1
Reactant: N#Cc1ccc(C(=O)C(C(=O)[O-])C2c3ccccc3Oc3ccccc32)cc1
Solvent: CS(C)=O
Solvent: O
Product: N#Cc1ccc(C(=O)CC2C=COc3ccccc32)cc1
Temperature: 190 °C

Procedure:
2-(4-Cyanobenzoyl)-2-(9H-xanthen-9-yl)acetate (8.1 g, 20.4 mmol) was dissolved in dimethylsulfoxide (100 ml),water (0.74 ml) was added and the resulting solution heated at 190° C., under N2 for 45 min. The cooled yellow solution was diluted with water and then extracted with ethyl acetate, washing with water then drying over magnesium sulphate, filtration and evaporation in vacuo gave 4-[2-(4H-benzopyran-4-yl)acetyl]benzonitrile as a yellow solid, m.p. 111° C.
Reaction SMILES: [N+:1]([C:4]1[CH:12]=[C:11]2[C:7]([CH2:8][CH2:9][C:10]2=[O:13])=[CH:6][CH:5]=1)([O-])=O.[H][H]>CCO.[Ni]>[NH2:1][C:4]1[CH:12]=[C:11]2[C:7]([CH2:8][CH2:9][C:10]2=[O:13])=[CH:6][CH:5]=1
Reactant: O=C1CCc2ccc([N+](=O)[O-])cc21
Reactant: [H][H]
Agent: [Ni]
Solvent: CCO
Product: Nc1ccc2c(c1)C(=O)CC2

Procedure:
A mixture of 6-nitroindan-1-one (1 part) and Raney-Ni in EtOH is treated with hydrogen (60 psi) for several hours. The catalyst is removed and the solvent evaporated to give 6-aminoindan-1-one. A solution of the aminoindanone (1 part) in a mixture of pyridine (16 parts), 4-dimethylaminopyridine (0.15 parts), and CH2Cl2 is treated with a solution of an acyl chloride (1.2 parts) and the reaction is stirred overnight. The reaction is poured into ice-water, the organic layer separated and consecutively washed with saturated aqueous sodium bicarbonate and brine. The organics are dried and the solvent evaporated to give the 6-carboxamido-indan-1-one. A solution of this product (1 part) in a mixture of EtOH and NH3 (5 parts) is treated with hydrogen (60 psi) in the presence of Pd--C-sulfided. After several hours, the catalyst is removed and the solvent evaporated to give 1-amino-6-carboxamido-indane. A solution of the indane (1 part) in a mixture of pyridine (16 parts), 4-dimethylaminopyridine (0.15 parts), and CH2Cl2 is treated with a solution of a benzoyl chloride (1.2 parts) and the reaction stirred over night. The reaction is poured into ice-water, the organic layer separated and consecutively washed with saturated aqueous sodium bicarbonate and brine. The organics are dried and the solvent evaporated to give the 1-benzamido-6-carboxamido-indane.
Reaction SMILES: [C:1]([NH:4][C:5]([CH2:24][CH2:25][C:26]1[CH:31]=[CH:30][C:29]([CH:32]=[O:33])=[CH:28][CH:27]=1)([CH2:15][O:16][Si:17]([C:20]([CH3:23])([CH3:22])[CH3:21])([CH3:19])[CH3:18])[CH2:6][O:7][Si:8]([C:11]([CH3:14])([CH3:13])[CH3:12])([CH3:10])[CH3:9])(=[O:3])[CH3:2].Br[CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1>>[C:1]([NH:4][C:5]([CH2:24][CH2:25][C:26]1[CH:31]=[CH:30][C:29]([CH:32]([OH:33])[CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)=[CH:28][CH:27]=1)([CH2:15][O:16][Si:17]([C:20]([CH3:21])([CH3:22])[CH3:23])([CH3:19])[CH3:18])[CH2:6][O:7][Si:8]([C:11]([CH3:14])([CH3:13])[CH3:12])([CH3:10])[CH3:9])(=[O:3])[CH3:2]
Reactant: BrCCCCCc1ccccc1
Reactant: CC(=O)NC(CCc1ccc(C=O)cc1)(CO[Si](C)(C)C(C)(C)C)CO[Si](C)(C)C(C)(C)C
Product: CC(=O)NC(CCc1ccc(C(O)CCCCCc2ccccc2)cc1)(CO[Si](C)(C)C(C)(C)C)CO[Si](C)(C)C(C)(C)C
Yield: 69.2 %

Procedure:
2-Acetamido-1,3-bis(tert-butyldimethylsilyloxy)-2-(2-(4-formylphenyl)ethyl)propane (3.0 g) and 1-bromo-5-phenylpentane (4.1 g) were reacted and treated in the same manner as in Working example 1(6) to give the title compound (2.7 g) as a pale yellow oily substance.
Reaction SMILES: [F:1][C:2]1([F:18])[C@H:6]([OH:7])[C@@H:5]([CH2:8][OH:9])[O:4][C@H:3]1[N:10]1[CH:17]=[CH:16][C:14]([NH2:15])=[N:13][C:11]1=[O:12].Cl[Si](C)(C)C.[CH2:24]([CH:27]([CH2:31][CH2:32][CH3:33])[C:28](O)=[O:29])[CH2:25][CH3:26].C(O)C>N1C=CC=CC=1.C(#N)C.O>[F:18][C:2]1([F:1])[C@H:6]([OH:7])[C@@H:5]([CH2:8][OH:9])[O:4][C@H:3]1[N:10]1[CH:17]=[CH:16][C:14]([NH:15][C:28](=[O:29])[CH:27]([CH2:31][CH2:32][CH3:33])[CH2:24][CH2:25][CH3:26])=[N:13][C:11]1=[O:12]
Reactant: Nc1ccn([C@@H]2O[C@H](CO)[C@@H](O)C2(F)F)c(=O)n1
Reactant: CCCC(CCC)C(=O)O
Agent: C[Si](C)(C)Cl
Solvent: c1ccncc1
Solvent: CC#N
Solvent: O
Product: CCCC(CCC)C(=O)Nc1ccn([C@@H]2O[C@H](CO)[C@@H](O)C2(F)F)c(=O)n1
Temperature: 0 °C

Procedure:
Dissolve 2′,2′-difluoro-2′-deoxycytidine (10.0 g, 38.0 mmol) in anhydrous pyridine (100 mL) and cool to 0° C. while stirring under nitrogen. Add chlorotrimethylsilane (24.0 mL, 190.0 mmol) dropwise, maintaining an internal temperature <5° C. Continue stirring at 0° C. for 2 hours. In a separate flask, dissolve 2-propylpentanoic acid (6.0 g, 41.8 mmol) in anhydrous acetonitrile (100 mL). Add 1,1-carbonyldiimidazole (6.8 g, 41.8 mmol) in small portions over 30 minutes and stir for 2 hours. Add this acetonitrile solution dropwise to the pyridine solution at 0° C. and allow the reaction to come to ambient temperature. Heat the reaction at 45° C. overnight then cool to 30-35° C. and add 100 mL absolute ethanol and heat at 45° C. for 30 minutes. Add 50 mL water and heat at 45° C. for 5 hours then cool to ambient temperature and concentrate in vacuo. Partition the crude residue between ethyl acetate and water. Acidify to pH ˜2 with phosphoric acid and separate the organic layer. Back extract the aqueous layer with additional ethyl acetate. Combine the organic solutions and wash with saturated sodium bicarbonate solution and saturated sodium chloride solution, dry over magnesium sulfate and concentrate in vacuo. Purify by silica gel chromatography (120 g) eluting with a gradient of 30% to 60% ethyl acetate in methylene chloride. Isolate desired product as a white crushable foam (11.2 g, 77% yield).
Reaction SMILES: [C:1]([O:5][C:6]([C:8]1([CH3:29])[N:12]2[C:13](=[O:28])[C:14]([NH:17][C:18]([O:20][CH2:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)=[O:19])=[CH:15][N:16]=[C:11]2[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:30](OC(NC1C(=O)N2[C@H](C(OC(C)(C)C)=O)CCC2=NC=1)=O)C1C=CC=CC=1.C(I)C>>[C:1]([O:5][C:6]([C:8]1([CH2:29][CH3:30])[N:12]2[C:13](=[O:28])[C:14]([NH:17][C:18]([O:20][CH2:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)=[O:19])=[CH:15][N:16]=[C:11]2[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)C1(C)CCc2ncc(NC(=O)OCc3ccccc3)c(=O)n21
Reactant: CC(C)(C)OC(=O)[C@@H]1CCc2ncc(NC(=O)OCc3ccccc3)c(=O)n21
Solvent: CCI
Product: CCC1(C(=O)OC(C)(C)C)CCc2ncc(NC(=O)OCc3ccccc3)c(=O)n21
Yield: 18 %

Procedure:
According to the procedure for the preparation of intermediate 19a, alkylation of intermediate 1g (250 mg, 0.649 mmol) with ethyl iodide afforded 47 mg (18%) of intermediate 22a. MS (ESI) 414.4 (M+H+), 436.4 (M+Na+).
Reaction SMILES: [N:1]12[CH2:9][CH2:8][CH:5]([CH2:6][CH2:7]1)[N:4]([C:10]1[N:15]=[CH:14][C:13]([NH:16][C:17](=[O:27])[C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[N+:24]([O-])=O)=[CH:12][N:11]=1)[CH2:3][CH2:2]2.N>[Pd].CO>[NH2:24][C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=1[C:17]([NH:16][C:13]1[CH:12]=[N:11][C:10]([N:4]2[CH:5]3[CH2:6][CH2:7][N:1]([CH2:9][CH2:8]3)[CH2:2][CH2:3]2)=[N:15][CH:14]=1)=[O:27]
Reactant: O=C(Nc1cnc(N2CCN3CCC2CC3)nc1)c1ccccc1[N+](=O)[O-]
Agent: [Pd]
Agent: N
Solvent: CO
Product: Nc1ccccc1C(=O)Nc1cnc(N2CCN3CCC2CC3)nc1
Reaction time: 72 h

Procedure:
A mixture of N-[2-(1,4-diaza-bicyclo[3.2.2]non-4-yl)-pyrimidin-5-yl]-2-nitro-benzamide (4.0 g, 9.9 mmol), palladium on carbon (100 mg, 10%) and methanol (100 ml) was stirred under hydrogen for 3 days. The mixture was neutralized by adding aqueous ammonia and extracted with chloroform. The mixture was dried and evaporated. The yellow oil was mixed with ethanol (25 ml) and hydrochloric acid (3 ml, 3 M). The mixture was cooled on an ice bath. The crystals were filtered and washed with ethanol followed by diethylether. Yield 2.27 g (61%).
Reaction SMILES: Br[C:2]1[C:3]2[C:4]3[CH:17]=[CH:16][S:15][C:5]=3[C:6](=[O:14])[NH:7][C:8]=2[CH:9]=[CH:10][C:11]=1[O:12][CH3:13].[CH3:18][N:19]([CH3:38])[S:20]([C:23]1[CH:28]=[CH:27][C:26](B2OC(C)(C)C(C)(C)O2)=[CH:25][CH:24]=1)(=[O:22])=[O:21]>>[CH3:13][O:12][C:11]1[CH:10]=[CH:9][C:8]2[NH:7][C:6](=[O:14])[C:5]3[S:15][CH:16]=[CH:17][C:4]=3[C:3]=2[C:2]=1[C:26]1[CH:25]=[CH:24][C:23]([S:20]([N:19]([CH3:38])[CH3:18])(=[O:21])=[O:22])=[CH:28][CH:27]=1
Reactant: COc1ccc2[nH]c(=O)c3sccc3c2c1Br
Reactant: CN(C)S(=O)(=O)c1ccc(B2OC(C)(C)C(C)(C)O2)cc1
Product: COc1ccc2[nH]c(=O)c3sccc3c2c1-c1ccc(S(=O)(=O)N(C)C)cc1
Yield: 24.9 %

Procedure:
Following General Procedure B, 9-bromo-8-methoxythieno[2,3-c]quinolin-4(5H)-one (100 mg, 0.32 mmol) was reacted with N,N-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzenesulfonamide (110 mg, 0.35 mmol) to afford the desired product (33 mg, crude) as a brown solid: ESI MS m/z 415 [C20H8N2O4S2+H]+.
Reaction SMILES: [C:1]1([C:7]2[N:8]=[C:9]3[N:13]([C:14]=2[CH:15]=O)[C:12]2[CH2:17][CH2:18][CH2:19][CH2:20][C:11]=2[S:10]3)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:21]([NH:29][NH2:30])(=[O:28])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.Cl.C(O)C.N>O>[C:1]1([C:7]2[N:8]=[C:9]3[N:13]([C:14]=2[CH:15]=[N:30][NH:29][C:21](=[O:28])[C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[C:12]2[CH2:17][CH2:18][CH2:19][CH2:20][C:11]=2[S:10]3)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: O=Cc1c(-c2ccccc2)nc2sc3c(n12)CCCC3
Reactant: NNC(=O)c1ccccc1
Agent: Cl
Agent: N
Solvent: O
Solvent: CCO
Product: O=C(NN=Cc1c(-c2ccccc2)nc2sc3c(n12)CCCC3)c1ccccc1
Yield: 84 %

Procedure:
0.28 g of 5,6,7,8-tetrahydro-2-phenyl-3-formylimidazo[2,1-b]benzothiazole and 0.15 g of benzohydrazide were stirred over night in 20 ml of a 0.1N hydrochloric acid-ethanol solution at room temperature and the precipitated crystal obtained by filtration. The crystals were dissolved in water and the solution was made alkaline by ammonia solution, then extracted by chloroform. The extract was washed with water and dried, then the solvent was distilled off and the residue was crystallized from ethyl acetate to obtain the desired substance in an amount of 0.35 g (yield of 84.0%).
Reaction SMILES: [N+](=[C:3]([C:8]([O:10][CH3:11])=[O:9])[C:4]([O:6][CH3:7])=[O:5])=[N-].[C:12]([O:16][CH2:17][CH3:18])(=[O:15])[CH2:13][OH:14]>C(Cl)Cl.CC(O)=O.CC(O)=O.CC(O)=O.CC(O)=O.[Rh].[Rh]>[CH2:17]([O:16][C:12](=[O:15])[CH2:13][O:14][CH:3]([C:8]([O:10][CH3:11])=[O:9])[C:4]([O:6][CH3:7])=[O:5])[CH3:18]
Reactant: CCOC(=O)CO
Reactant: COC(=O)C(=[N+]=[N-])C(=O)OC
Agent: [Rh]
Solvent: ClCCl
Solvent: CC(=O)O
Product: CCOC(=O)COC(C(=O)OC)C(=O)OC
Temperature: 25 °C
Reaction time: 24 h
Yield: 100.1 %

Procedure:
To a solution of dimethyl diazopropanedioate (4 g, 25 mmol), prepared according to Peace, Carman, Wulfman, Synthesis, 658-661, (1971), in DCM (10 mL) was added ethyl glycolate (1.2 mL, 12.8 mmol) followed by rhodium (II) acetate dimer (2 g, 20% mol). The reaction mixture was stirred at room temperature for 24 h. The resulting suspension was filtered through a pad of Celite® and the solvent was removed in vacuo. The crude residue was purified by column chromatography (silica gel) using a 0-60% EtOAc/hexanes gradient to provide the desired product as an oil (3 g, 97%).
Reaction SMILES: C([O:5][C:6](=[O:36])[CH:7]=[CH:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][C:16]([F:19])([F:18])[F:17])=[C:11]([C:20]2[C:21]([CH3:35])=[CH:22][C:23]3[C:28]([CH3:30])([CH3:29])[O:27][C:26](=[O:31])[N:25]([CH2:32][CH3:33])[C:24]=3[CH:34]=2)[CH:10]=1)(C)(C)C>ClCCl.FC(F)(F)C(O)=O>[CH2:32]([N:25]1[C:24]2[CH:34]=[C:20]([C:11]3[CH:10]=[C:9]([CH:8]=[CH:7][C:6]([OH:36])=[O:5])[CH:14]=[CH:13][C:12]=3[O:15][C:16]([F:19])([F:17])[F:18])[C:21]([CH3:35])=[CH:22][C:23]=2[C:28]([CH3:30])([CH3:29])[O:27][C:26]1=[O:31])[CH3:33]
Reactant: CCN1C(=O)OC(C)(C)c2cc(C)c(-c3cc(C=CC(=O)OC(C)(C)C)ccc3OC(F)(F)F)cc21
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CCN1C(=O)OC(C)(C)c2cc(C)c(-c3cc(C=CC(=O)O)ccc3OC(F)(F)F)cc21

Procedure:
A solution of 0.068 g (0.15 mmol) of Compound 14F in 3 mL of dichloromethane and 2.5 mL of trifluoroacetic acid was stirred at room temperature overnight. The reaction mixture was then concentrated on the rotary evaporator to obtain 3-[3-(1-ethyl-4,4,6-trimethyl-2-oxo-1,4-dihydro-2H-benzo[d][1,3]oxazin-7-yl)-4-trifluoromethoxy-phenyl]-acrylic acid as a white solid (Compound 14, 0.06 g). MS (electrospray): mass calculated for C257H30F3NO5, 505.13; m/z found 506, [M+H]+.
Reaction SMILES: [Cl:1][C:2]1[N:3]=[C:4]([NH:22][CH2:23][CH:24]2[CH2:29][CH2:28][N:27]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:26][CH2:25]2)[C:5]2[C:10](I)=[CH:9][N:8]([S:12]([C:15]3[CH:21]=[CH:20][C:18]([CH3:19])=[CH:17][CH:16]=3)(=[O:14])=[O:13])[C:6]=2[N:7]=1.C([Sn](CCCC)(CCCC)[C:42]1[CH:47]=[CH:46][N:45]=[CH:44][CH:43]=1)CCC.O.CCOC(C)=O>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:1][C:2]1[N:3]=[C:4]([NH:22][CH2:23][CH:24]2[CH2:29][CH2:28][N:27]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:26][CH2:25]2)[C:5]2[C:10]([C:42]3[CH:47]=[CH:46][N:45]=[CH:44][CH:43]=3)=[CH:9][N:8]([S:12]([C:15]3[CH:21]=[CH:20][C:18]([CH3:19])=[CH:17][CH:16]=3)(=[O:14])=[O:13])[C:6]=2[N:7]=1
Reactant: Cc1ccc(S(=O)(=O)n2cc(I)c3c(NCC4CCN(C(=O)OC(C)(C)C)CC4)nc(Cl)nc32)cc1
Reactant: CCCC[Sn](CCCC)(CCCC)c1ccncc1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: O
Solvent: CCOC(C)=O
Solvent: C1COCCO1
Product: Cc1ccc(S(=O)(=O)n2cc(-c3ccncc3)c3c(NCC4CCN(C(=O)OC(C)(C)C)CC4)nc(Cl)nc32)cc1
Temperature: 100 °C
Reaction time: 4 h
Yield: 29 %

Procedure:
A solution of tert-butyl 4-((2-chloro-5-iodo-7-tosyl-7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)methyl)piperidine-1-carboxylate (336 mg, 0.520 mmol) in dioxane (4 mL) was degassed with Ar before being charged with 4-tributylstannylpyridine (452 mg, 1.23 mmol) and Pd(Ph3P)4 (110 mg, 0.095 mmol). The mixture was stirred at 100° C. for 4 h. Water and EtOAc were added. The organic phase was separated, dried over Na2SO4, concentrated in vacuo. The residue was purified by a flash column, eluted with EtOAc/hexane (0-100%) to give tert-butyl 4-((2-chloro-5-(pyridine-4-yl)-7-tosyl-7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)methyl)piperidine-1-carboxylate (90 mg).
Reaction SMILES: [O:1]1[CH2:4][CH:3](/[CH:5]=[N:6]/[S@:7]([C:9]([CH3:12])([CH3:11])[CH3:10])=[O:8])[CH2:2]1.[CH3:13][Mg]Br>ClCCl>[O:1]1[CH2:4][CH:3]([C@H:5]([NH:6][S@:7]([C:9]([CH3:12])([CH3:11])[CH3:10])=[O:8])[CH3:13])[CH2:2]1
Reactant: C[Mg]Br
Reactant: CC(C)(C)[S@](=O)/N=C/C1COC1
Solvent: ClCCl
Product: C[C@@H](N[S@@](=O)C(C)(C)C)C1COC1
Temperature: -76 °C
Reaction time: 3 h
Yield: 76.5 %

Procedure:
In a round-bottomed flask, (S)-2-methyl-propane-2-sulfinic acid 1-oxetan-3-yl-meth-(E)-ylideneamide (172 mg, 0.91 mmol) was dissolved in dichloromethane (3.6 ml). The colorless solution was cooled to −76° C. and methylmagnesium bromide (3.0 M in diethyl ether, 0.91 ml, 2.73 mmol) was added dropwise. The reaction mixture was stirred at −76° C. for 3 h and then allowed to warm slowly to room temperature overnight. The reaction was quenched with saturated NH4Cl-solution then extracted with EtOAc (2×). The combined organic layers were washed with water and brine then dried over sodium sulfate, filtered and concentrated to provide 143 mg (77%) of (S)-2-methyl-propane-2-sulfinic acid ((R)-1-oxetan-3-yl-ethyl)-amide as a light yellow oil which was used without further purification.
Reaction SMILES: [N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:3]([C:11]#[C:12][CH2:13][OH:14])[CH:2]=1.CC(C)([O-])C.[K+].[CH:21]1([N:27]([CH:31]2[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]2)[C:28](Cl)=[O:29])[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]1.[NH4+].[Cl-]>C1COCC1.CC(OC)(C)C>[CH:21]1([N:27]([CH:31]2[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]2)[C:28]([O:14][CH2:13][C:12]#[C:11][C:3]2[CH:2]=[N:1][C:10]3[C:5]([CH:4]=2)=[CH:6][CH:7]=[CH:8][CH:9]=3)=[O:29])[CH2:22][CH2:23][CH2:24][CH2:25][CH2:26]1
Reactant: O=C(Cl)N(C1CCCCC1)C1CCCCC1
Reactant: OCC#Cc1cnc2ccccc2c1
Agent: CC(C)(C)[O-]
Agent: [Cl-]
Agent: [K+]
Solvent: COC(C)(C)C
Solvent: C1CCOC1
Product: O=C(OCC#Cc1cnc2ccccc2c1)N(C1CCCCC1)C1CCCCC1
Temperature: 0 °C
Reaction time: 2 h

Procedure:
To a dry three-necked round-bottom flask equipped with nitrogen inlet and overhead stirrer was charged 3-(3-quinolyl)-2-propyn-1-ol (1 g, 5.4 mmol) in THF (10 ml) and the solution was cooled to 0° C. Potassium t-butoxide (0.67 g, 5.9 mmol) was then added followed by dicyclohexylcarbamoyl chloride (1.32 g, 5.4 mmol). The mixture was stirred for 2 hours at 0° C. and then allowed to warm up to room temperature over a period of 6 hours by which time the reaction was determined to be complete. The reaction mixture was worked up with MTBE (50 ml) and 10% NH4Cl (25 ml) and the organic layers were concentrated to an oil. The purity compared to the standard was 94% and was used as such. Yield 2 g (95%).
Reaction SMILES: [OH:1][C@@H:2]1[C:19]2[C@:14]([CH3:23])([CH2:15][CH2:16][C:17](=[O:22])[C:18]=2[CH2:20][CH3:21])[C@@H:13]2[C@H:4]([C@H:5]3[C@@:9]([CH2:11][CH2:12]2)([CH3:10])[C@@H:8]([O:24][C:25](=[O:27])[CH3:26])[CH2:7][CH2:6]3)[CH2:3]1.O[C@H]1C2[C@](C)(CCC(=O)C=2CC)[C@@H]2[C@H]([C@H]3[C@@](CC2)(C)[C@@H](OC(=O)C)CC3)C1.CC(C)=O.OS(O)(=O)=O.O=[Cr](=O)=O.C(Cl)Cl>CC(C)=O>[C:25]([O:24][C@H:8]1[CH2:7][CH2:6][C@H:5]2[C@H:4]3[C@H:13]([CH2:12][CH2:11][C@:9]12[CH3:10])[C@:14]1([CH3:23])[C:19](=[C:18]([CH2:20][CH3:21])[C:17](=[O:22])[CH2:16][CH2:15]1)[C:2](=[O:1])[CH2:3]3)(=[O:27])[CH3:26]
Reactant: CCC1=C2[C@@H](O)C[C@H]3[C@@H]4CC[C@H](OC(C)=O)[C@@]4(C)CC[C@@H]3[C@@]2(C)CCC1=O
Agent: O=[Cr](=O)=O
Agent: CCC1=C2[C@H](O)C[C@H]3[C@@H]4CC[C@H](OC(C)=O)[C@@]4(C)CC[C@@H]3[C@@]2(C)CCC1=O
Agent: O=S(=O)(O)O
Solvent: ClCCl
Solvent: CC(C)=O
Product: CCC1=C2C(=O)C[C@H]3[C@@H]4CC[C@H](OC(C)=O)[C@@]4(C)CC[C@@H]3[C@@]2(C)CCC1=O
Yield: 92 %

Procedure:
To a solution of a 6α-hydroxy-17β-acetoxy-4-ethylandrost-4-en-3-one and 6β-hydroxy-17β-acetoxy-4-ethylandrost-4-en-3-one (510 mg) in acetone (34 ml) cooled at 0° C., Jones reagent (1.1 ml) was added dropwise. 5 min after completion of the addition, DCM (140 ml) was added and the mixture was washed with 10% Na2SO3 aqueous solution, 5% aqueous NaHCO3 solution, and brine. The organic phase was dried over Na2SO4, and evaporated to dryness to give 17β-acetoxy-4-ethylandrost-4-en-3,6-dione (465 g, 92%).
Reaction SMILES: [OH:1][N:2]=[CH:3][C:4]1[CH:16]=[CH:15][C:7]([C:8]([NH:10][CH:11]=[N:12][O:13][CH3:14])=[O:9])=[C:6]([CH3:17])[CH:5]=1.ClN1C(=O)CCC1=O.[Cl:26][C:27]1[CH:28]=[C:29]([C:37]([C:39]([F:42])([F:41])[F:40])=[CH2:38])[CH:30]=[C:31]([C:33]([F:36])([F:35])[F:34])[CH:32]=1.C(=O)([O-])O.[K+]>COCCOC.O>[Cl:26][C:27]1[CH:28]=[C:29]([C:37]2([C:39]([F:40])([F:41])[F:42])[O:1][N:2]=[C:3]([C:4]3[CH:16]=[CH:15][C:7]([C:8]([NH:10][CH:11]=[N:12][O:13][CH3:14])=[O:9])=[C:6]([CH3:17])[CH:5]=3)[CH2:38]2)[CH:30]=[C:31]([C:33]([F:34])([F:35])[F:36])[CH:32]=1
Reactant: CON=CNC(=O)c1ccc(C=NO)cc1C
Reactant: C=C(c1cc(Cl)cc(C(F)(F)F)c1)C(F)(F)F
Agent: O=C([O-])O
Agent: O=C1CCC(=O)N1Cl
Agent: [K+]
Solvent: COCCOC
Solvent: O
Product: CON=CNC(=O)c1ccc(C2=NOC(c3cc(Cl)cc(C(F)(F)F)c3)(C(F)(F)F)C2)cc1C
Temperature: 70 °C
Reaction time: 0.75 h
Yield: 11.7 %

Procedure:
In a solution of 81 mg of 4-hydroxyiminomethyl-N-(methoxyiminomethyl)-2-methyl benzoic acid amide in 10 ml of 1,2-dimethoxyethane, 60 mg of N-chlorosuccinimide was added, and stirred at 70° C. for 45 minutes. Then, the reaction mixture was left and cooled to room temperature, and then 60 mg of 3-chloro-5-trifluoromethyl-1-(1-trifluoromethylethenyl)benzene, 40 mg of potassium hydrogen carbonate and 3 drops of water were added, and continued to stir at room temperature further for 15 hours. After the completion of the reaction, the reaction mixture was poured in 10 mL of water, and extracted with ethyl acetate (15 mL×2). The combined organic phases were dehydrated with and dried over saturated sodium chloride aqueous solution and then anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified with silica gel column chromatography that were eluated with ethyl acetate-hexane (gradient of 1:5 to 1:3) to obtain 13 mg of the aimed product as colorless resinous substance.
Reaction SMILES: [CH3:1][C@H:2]1[NH:7][C@@H:6]([CH3:8])[CH2:5][N:4]([C:9]2[N:14]=[C:13]([NH2:15])[C:12]([O:16][CH3:17])=[CH:11][CH:10]=2)[CH2:3]1.N1C=CC=CC=1.[Br:24][C:25]1[CH:30]=[CH:29][C:28]([S:31](Cl)(=[O:33])=[O:32])=[CH:27][CH:26]=1>C(Cl)Cl>[Br:24][C:25]1[CH:30]=[CH:29][C:28]([S:31]([NH:15][C:13]2[C:12]([O:16][CH3:17])=[CH:11][CH:10]=[C:9]([N:4]3[CH2:3][C@H:2]([CH3:1])[NH:7][C@H:6]([CH3:8])[CH2:5]3)[N:14]=2)(=[O:33])=[O:32])=[CH:27][CH:26]=1
Reactant: COc1ccc(N2C[C@@H](C)N[C@@H](C)C2)nc1N
Reactant: O=S(=O)(Cl)c1ccc(Br)cc1
Solvent: ClCCl
Solvent: c1ccncc1
Product: COc1ccc(N2C[C@@H](C)N[C@@H](C)C2)nc1NS(=O)(=O)c1ccc(Br)cc1
Temperature: 25 °C
Yield: 47.8 %

Procedure:
6-[(3R,5S)-3,5-Dimethyl-1-piperazinyl]-3-(methyloxy)-2-pyridinamine (D7, Method E)(1.5 g, 6.35 mmol) was dissolved in DCM (15 mL) and pyridine (15 mL) and then cooled to 0° C. 4-Bromobenzenesulfonyl chloride (3.04 g, 11.9 mmol), dissolved in DCM (8 mL) was then added dropwise and the reaction then allowed to warm to room temperature overnight. The reaction was then evaporated to a minimum and redissolved in DCM (100 mL) and washed with water (50 mL). Aqueous layer was extracted with DCM (100 mL) and combined organic extracts washed with saturated sodium hydrogen carbonate (2×100 mL) and brine (100 mL). The organic layer was dried (MgSO4) and evaporated to give a brown solid which was triturated with ethyl acetate (3×10 mL) to give the title compound as a pale yellow powder (D17) (1.382 g). MS (ES+) m/e 455/457 [M+H]+.
Reaction SMILES: [CH3:1]/[C:2](/[CH2:9][CH2:10]/[CH:11]=[C:12](/[CH3:19])\[CH2:13][CH2:14][CH:15]=[C:16]([CH3:18])[CH3:17])=[CH:3]/[C:4](OCC)=[O:5].[H-].C([Al+]CC(C)C)C(C)C>C1(C)C=CC=CC=1>[CH3:1]/[C:2](/[CH2:9][CH2:10]/[CH:11]=[C:12](/[CH3:19])\[CH2:13][CH2:14][CH:15]=[C:16]([CH3:18])[CH3:17])=[CH:3]/[CH2:4][OH:5]
Reactant: CCOC(=O)/C=C(/C)CC/C=C(/C)CCC=C(C)C
Agent: CC(C)C[Al+]CC(C)C
Agent: [H-]
Solvent: Cc1ccccc1
Product: CC(C)=CCC/C(C)=C\CC/C(C)=C\CO
Temperature: 0 °C
Reaction time: 1 h

Procedure:
A solution of 1 g (0.0038 mol) of ethyl (2Z,6Z)-3,7,11-trimethyl-2,6,10-dodecatrienoate in 8 ml of toluene is treated dropwise at -5° to -10° with 9.45 ml of a solution of diisobutylaluminium hydride in toluene (1.2 mol/l, i.e. 3.0 mol equivalents). The solution is stirred at the same temperature for 1 hour under argon. The reaction mixture is poured into an ice-water mixture and extracted with ether. After drying and removing the solvent the residue is chromatographed on silica gel with ether-hexane 1:1. There is obtained (2Z,6Z)-3,7,11-trimethyl-2,6,10-dodecatrien-1-ol which has the following bands in the IR spectrum: 3327 cm-1, 1666 cm-1, 1448 cm-1, 1379 cm-1, 999 cm-1.
Reaction SMILES: [N:1]12[CH2:8][CH2:7][CH:4]([CH2:5][CH2:6]1)[CH:3]([OH:9])[CH2:2]2.Cl[C:11]1[N:16]=[N:15][C:14]([C:17]2[C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[NH:19][CH:18]=2)=[CH:13][CH:12]=1>>[NH:19]1[C:20]2[C:25](=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:17]([C:14]2[N:15]=[N:16][C:11]([O:9][CH:3]3[CH:4]4[CH2:7][CH2:8][N:1]([CH2:6][CH2:5]4)[CH2:2]3)=[CH:12][CH:13]=2)=[CH:18]1
Reactant: Clc1ccc(-c2c[nH]c3ccccc23)nn1
Reactant: OC1CN2CCC1CC2
Product: c1ccc2c(-c3ccc(OC4CN5CCC4CC5)nn3)c[nH]c2c1

Procedure:
3-Quinuclidinol (Aldrich, 254 mg, 2 mmol) was coupled with 3-(6-chloropyridazin-3-yl)-1H-indole (Bionet, 458 mg, 2 mmol) at 60° C. for 16 hours according to the procedure of Example 7A. The title compound was purified by preparative HPLC (Xterra™, column, Xterra RP-18, 5 μm, 30×100 mm. Eluting Solvent, MeCN/H2O (NH4HCO3, 0.1 M, pH=10), (v. 90/10 to 10/90 over 20 min.) Flow rate, 75 mL/min., uv, 250 nm) as solid (400 mg, 63%). 1H NMR (MeOH-D4, 300 MHz) 1.50-1.64 (m, 1H), 1.71-1.93 (m, 2H), 2.00-2.15 (m, 1H), 2.29-2.36 (m, 1H), 2.78-3.04 (m, 5H), 3.43-3.55 (m, 1H), 5.24-5.32 (m, 1H), 7.12-7.25 (m, 3H), 7.42-7.48 (m, 1H), 7.87 (s, 1H), 8.01 (d, J=9.2 Hz, 1H), 8.26-8.33 (m, 1H) ppm. MS (DCI/NH3) m/z 321 (M+H)+.