Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[C:15]([Cl:16])=[CH:14][CH:13]=[CH:12][C:3]=1[CH2:4][CH:5]([C:8](=O)[CH2:9][CH3:10])[C:6]#[N:7].O.[NH2:18][NH2:19]>CCO>[Cl:1][C:2]1[C:15]([Cl:16])=[CH:14][CH:13]=[CH:12][C:3]=1[CH2:4][C:5]1[C:8]([CH2:9][CH3:10])=[N:18][NH:19][C:6]=1[NH2:7]
Reactant: NN
Reactant: CCC(=O)C(C#N)Cc1cccc(Cl)c1Cl
Solvent: O
Solvent: CCO
Product: CCc1n[nH]c(N)c1Cc1cccc(Cl)c1Cl
Temperature: 90 °C
Reaction time: 20 h
Yield: 39.4 %

Procedure:
To a solution of 2-(2,3-dichlorobenzyl)-3-oxopentanenitrile (1.2 g, 4.7 mmol) in EtOH (10 mL) was added hydrazine hydrate (285 mg, 5.7 mmol) and stirred at 90° C. for 20 h. The mixture was cooled to room temperature and concentrated. The residue was purified by silica gel column (PE:EA=10:1) to give the titled compound (500 mg, 36% over two steps); LC/MS: MS (ES+) m/e 270 (MH+); 1H NMR (300 MHz, CDCl3) δ ppm 1.16 (t, J=7.5 Hz, 3H), 2.53 (q, J=7.5 Hz, 2H), 3.78 (s, 2H), 4.26 (s, 2H), 6.94-6.97 (m, 1H), 7.10 (t, J=7.8 Hz, 1H), 7.32-7.35 (m, 1H).
Reaction SMILES: C(OC(=O)[NH:7][CH:8]1[CH2:13][CH2:12][CH2:11][N:10]([C:14](=[O:38])[C@@H:15]([N:17]2[CH2:21][CH2:20][C@H:19]([NH:22][S:23]([C:26]3[CH:35]=[CH:34][C:33]4[C:28](=[CH:29][CH:30]=[C:31]([Cl:36])[CH:32]=4)[CH:27]=3)(=[O:25])=[O:24])[C:18]2=[O:37])[CH3:16])[CH2:9]1)(C)(C)C.FC(F)(F)C(O)=O>C(Cl)Cl>[NH2:7][CH:8]1[CH2:13][CH2:12][CH2:11][N:10]([C:14](=[O:38])[C@@H:15]([N:17]2[CH2:21][CH2:20][C@H:19]([NH:22][S:23]([C:26]3[CH:35]=[CH:34][C:33]4[C:28](=[CH:29][CH:30]=[C:31]([Cl:36])[CH:32]=4)[CH:27]=3)(=[O:25])=[O:24])[C:18]2=[O:37])[CH3:16])[CH2:9]1
Reactant: C[C@@H](C(=O)N1CCCC(NC(=O)OC(C)(C)C)C1)N1CC[C@H](NS(=O)(=O)c2ccc3cc(Cl)ccc3c2)C1=O
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: C[C@@H](C(=O)N1CCCC(N)C1)N1CC[C@H](NS(=O)(=O)c2ccc3cc(Cl)ccc3c2)C1=O
Temperature: 25 °C
Reaction time: 2 h
Yield: 76.6 %

Procedure:
tert-Butyl1-[(2S)-2-((3S)-3-{[(6-chloro-2-naphthyl)sulfonyl]amino}-2-oxopyrrolidin-1-yl)propanoyl]piperidin-3-ylcarbamate (0.6 g) was dissolved in DCM (11 ml) and trifluoroacetic acid (11 ml) was added. The mixture was stirred at room temperature for 2 h and then concentrated under reduced pressure. The residue was dissolved in water (5 ml) and ammonia solution (0.88%; 1 ml) added. The resultant aqueous mixture was extracted with DCM. The combined organic extracts were dried (over magnesium sulphate), filtered and concentrated under reduced pressure to give the title compound (0.38 g) as a white foam.
Reaction SMILES: [N:1]1([CH2:6][CH2:7][CH2:8][C:9]2[CH:14]=[CH:13][C:12]([C:15](=[O:17])[CH3:16])=[CH:11][CH:10]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[CH:18](=O)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.C(=O)([O-])[O-].[K+].[K+]>CO.O.C(OCC)(=O)C>[C:19]1(/[CH:18]=[CH:16]/[C:15]([C:12]2[CH:11]=[CH:10][C:9]([CH2:8][CH2:7][CH2:6][N:1]3[CH2:5][CH2:4][CH2:3][CH2:2]3)=[CH:14][CH:13]=2)=[O:17])[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1
Reactant: O=Cc1ccccc1
Reactant: CC(=O)c1ccc(CCCN2CCCC2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Solvent: O
Solvent: CCOC(C)=O
Product: O=C(/C=C/c1ccccc1)c1ccc(CCCN2CCCC2)cc1
Yield: 81.5 %

Procedure:
4 g of 4'-[3-(1-pyrrolidinyl)propyl]acetophenone and 2 g of benzaldehyde were dissolved in 80 ml of methanol and treated with a solution of 9.55 g of potassium carbonate in 38 ml of water within 15 minutes while cooling with an ice bath. The mixture was then left to react at room temperature for 18 hours and at about 40° for a further 18 hours. The reaction mixture was taken up in 200 ml of ethyl acetate and extracted with 100 ml of water. The aqueous phase was again extracted with 200 ml of ethyl acetate and the organic phases were again extracted with 100 ml of semi-saturated sodium chloride solution. The combined organic phases were dried over magnesium sulphate and evaporated. The residue was chromatographed on silica gel with acetone. There were obtained 4.5 g (81%) of (E)-3-phenyl-4'-[3-(1-pyrrolidinyl)propyl]acrylophenone as a yellow oil; mass spectrum m/e: M+ 319 (7.1), 131 (1.4), 84 (100), 42 (7.5). For the formation of the hydrochloride, the free amine was dissolved in a small amount of ethanol and treated with 10M ethanolic hydrochloric acid solution. After recrystallization of the resulting material from isopropanol there was obtained the pure hydrochloride; m.p. 211°-213°.
Reaction SMILES: B(Br)(Br)Br.C[O:6][C:7]1[CH:12]=[C:11]([O:13]C)[CH:10]=[CH:9][C:8]=1[CH3:15].C(OCC)(=O)C.[OH-].[Na+]>CCCCC>[OH:6][C:7]1[CH:12]=[C:11]([OH:13])[CH:10]=[CH:9][C:8]=1[CH3:15]
Reactant: COc1ccc(C)c(OC)c1
Agent: BrB(Br)Br
Agent: [Na+]
Agent: [OH-]
Solvent: CCCCC
Solvent: CCOC(C)=O
Product: Cc1ccc(O)cc1O
Temperature: 25 °C
Reaction time: 2 h
Yield: 94.1 %

Procedure:
Boron tribromide (3.1 ml, 3.2 mmol) was added to a solution of 2,4-dimethoxytoluene (1 g, 6.5 mmol) in pentane (10 ml) at −70° C. The reaction mixture was allowed to warm to ambient temperature and the mixture stirred for a further 2 hours. Ice water and ethyl acetate were then added and the aqueous layer basified to pH9.5 with 2M aqueous sodium hydroxide. After stirring for 10 minutes, the organic layer was separated and the aqueous layer extracted with ethyl acetate. The combined organic extract was washed with brine, dried (MgSO4) and the solvent removed by evaporation. The residue was purified by flash chromatography eluting with methylene chloride/ethyl acetate (9/1) to give 2,4-dihydroxytoluene (759 mg, 94%) as a white solid.
Reaction SMILES: I[C:2]1[N:3]=[CH:4][N:5]([C:7]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:6]=1.C([Mg]Br)C.[CH2:30]([Sn:34](Cl)([CH2:39][CH2:40][CH2:41][CH3:42])[CH2:35][CH2:36][CH2:37][CH3:38])[CH2:31][CH2:32][CH3:33]>ClCCl>[CH2:39]([Sn:34]([CH2:30][CH2:31][CH2:32][CH3:33])([CH2:35][CH2:36][CH2:37][CH3:38])[C:2]1[N:3]=[CH:4][N:5]([C:7]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:6]=1)[CH2:40][CH2:41][CH3:42]
Reactant: Ic1cn(C(c2ccccc2)(c2ccccc2)c2ccccc2)cn1
Reactant: CCCC[Sn](Cl)(CCCC)CCCC
Agent: CC[Mg]Br
Solvent: ClCCl
Product: CCCC[Sn](CCCC)(CCCC)c1cn(C(c2ccccc2)(c2ccccc2)c2ccccc2)cn1
Yield: 33.8 %

Procedure:
To a solution of 4-Iodo-1-trityl-1H-imidazole (5.0 g, 11.6 mmol) in dichloromethane (100 ml) added Ethylmagnesium bromide (3M in diethyl ether) (4.6 ml, 13.9 mmol). Stirred the reaction under argon atmosphere at room temperature for 1 h. At this point added tributyltin chloride (4.1 ml, 13.9 mmol) to the reaction mixture and left the resulting mixture stirring at room temperature overnight. The reaction mixture was diluted with dichloromethane (100 ml), successively washed with saturated ammonium chloride (100 ml), water (100 ml) and brine (100 ml). The organic phase was dried (sodium sulfate), filtered and concentrated in-vacuo to yield 4-Tributylstannyl-1-trityl-1H-imidazole (2.35 g) as a white waxy solid.
Reaction SMILES: [CH3:1][N:2]([CH2:4][C:5]1[CH:10]=[CH:9][N:8]=[C:7]([CH2:11][S:12][CH2:13][CH2:14][NH2:15])[CH:6]=1)[CH3:3].[N+](N[C:20]1[NH:25][C:24](=[O:26])[C:23]([CH2:27][C:28]2[CH:33]=[CH:32][N:31]([CH3:34])[C:30](=[O:35])[CH:29]=2)=[CH:22][N:21]=1)([O-])=O.N1C=CC=CC=1>C(O)C>[CH3:3][N:2]([CH2:4][C:5]1[CH:10]=[CH:9][N:8]=[C:7]([CH2:11][S:12][CH2:13][CH2:14][NH:15][C:20]2[NH:25][C:24](=[O:26])[C:23]([CH2:27][C:28]3[CH:33]=[CH:32][N:31]([CH3:34])[C:30](=[O:35])[CH:29]=3)=[CH:22][N:21]=2)[CH:6]=1)[CH3:1]
Reactant: CN(C)Cc1ccnc(CSCCN)c1
Reactant: Cn1ccc(Cc2cnc(N[N+](=O)[O-])[nH]c2=O)cc1=O
Solvent: c1ccncc1
Solvent: CCO
Product: CN(C)Cc1ccnc(CSCCNc2ncc(Cc3ccn(C)c(=O)c3)c(=O)[nH]2)c1
Yield: 56.5 %

Procedure:
2-[4-(Dimethylaminomethyl)pyrid-2-ylmethylthio]ethylamine (0.63 g) and 2-nitroamino-5-(1-methyl-2-oxopyridin-4-ylmethyl)pyrimidin-4-one (0.69 g) were refluxed in ethanol (12 ml) for 72 hours. As the reaction was not complete, the ethanol was replaced by pyridine (12 ml) and the solution refluxed for a further 6 hours. The reaction mixture was evaporated under reduced pressure to afford a residue which was washed with diethyl ether and recrystallised from isopropanol/ether to give 2-[2-[4-(dimethylaminomethyl)pyrid-2-ylmethylthio]ethylamino]-5-(1-methyl-2-oxopyridin-4-ylmethyl)pyrimidin-4-one (0.62 g), m.p. 137°-139° C.
Reaction SMILES: [N+:1]([C:4]1[CH:13]=[CH:12][CH:11]=[C:10]2[C:5]=1[CH:6]=[CH:7][C:8](Cl)=[N:9]2)([O-])=O.[CH3:15][O:16][C:17]1[CH:24]=[CH:23][CH:22]=[CH:21][C:18]=1[CH2:19][NH2:20].[NH:25]1[C:33]2[CH:32]=[CH:31][CH:30]=[C:29]([CH:34]=O)[C:28]=2[CH:27]=[CH:26]1>>[NH:25]1[C:33]2[C:28](=[C:29]([CH2:34][NH:1][C:4]3[C:5]4[CH:6]=[CH:7][C:8]([NH:20][CH2:19][C:18]5[CH:21]=[CH:22][CH:23]=[CH:24][C:17]=5[O:16][CH3:15])=[N:9][C:10]=4[CH:11]=[CH:12][CH:13]=3)[CH:30]=[CH:31][CH:32]=2)[CH:27]=[CH:26]1
Reactant: COc1ccccc1CN
Reactant: O=Cc1cccc2[nH]ccc12
Reactant: O=[N+]([O-])c1cccc2nc(Cl)ccc12
Product: COc1ccccc1CNc1ccc2c(NCc3cccc4[nH]ccc34)cccc2n1

Procedure:
The title compound, MS: m/e=409.5 (M+H+), was prepared from 5-nitro-2-chloroquinoline, 2-methoxybenzylamine and 4-indole-carboxaldehyde as described in example 26.
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([CH3:8])[C:5]([N+:9]([O-:11])=[O:10])=[CH:4][CH:3]=1.[CH3:12][NH:13][CH3:14].O>CO.CCOC(C)=O>[CH3:12][N:13]([CH3:14])[C:2]1[CH:3]=[CH:4][C:5]([N+:9]([O-:11])=[O:10])=[C:6]([CH3:8])[N:7]=1
Reactant: CNC
Reactant: Cc1nc(Cl)ccc1[N+](=O)[O-]
Solvent: O
Solvent: CO
Solvent: CCOC(C)=O
Product: Cc1nc(N(C)C)ccc1[N+](=O)[O-]
Temperature: 60 °C
Yield: 95 %

Procedure:
To a solution of 6-chloro-2-methyl-3-nitropyridine (0.5 g, 2.9 mmol) in MeOH (5 mL) was added dimethylamine in water (1.2 mL, 11.6 mmol) and the reaction mixture was heated at 60° C. for 4 h. The reaction mixture was then diluted with EtOAc, extracted with water and washed with brine. The organic layer was dried over sodium sulphate and concentrated to yield the title compound (0.5 g, 95%). LCMS (ES+) 182 (M+H)+, RT 2.74 minutes (method 1).
Reaction SMILES: [C:1]([C:3]1[CH:10]=[CH:9][C:6]([CH:7]=[O:8])=[CH:5][CH:4]=1)#[N:2].[C:11]([C:14]1[CH:21]=[CH:20][C:17]([C:18]#[N:19])=[CH:16][CH:15]=1)(=O)[CH3:12]>>[C:18]([C:17]1[CH:20]=[CH:21][C:14]([CH:11]=[CH:12][C:7]([C:6]2[CH:9]=[CH:10][C:3]([C:1]#[N:2])=[CH:4][CH:5]=2)=[O:8])=[CH:15][CH:16]=1)#[N:19]
Reactant: CC(=O)c1ccc(C#N)cc1
Reactant: N#Cc1ccc(C=O)cc1
Product: N#Cc1ccc(C=CC(=O)c2ccc(C#N)cc2)cc1

Procedure:
Part A. Employing methods similar to Example 1 Part A but using 4-cyano benzaldehyde (1.80 gm, 13.8 mmol) and 4-acetyl benzonitrile (1.0 gm, 6.89 mmol), 4-[3-(4-cyanophenyl)-1-oxo-2-propenyl]benzonitrile was isolated as a pale yellow powder, 0.4 gm (20%) MS 259(M+H)+ 1 H NMR (CDCl3): 7.78(d, 2H), 7.6(t, 1H), 7.5-7.0(m, 7H).
Reaction SMILES: C(OC([N:8]([CH3:18])[C@@H:9]([CH2:13][C:14](C)(C)C)[C:10]([OH:12])=O)=O)(C)(C)C.[F:19][C:20]([F:37])([F:36])[C:21]1[CH:26]=[CH:25][C:24]([N:27]2[CH2:31][C@@H:30]3[C@@H:32]([NH2:35])[CH2:33][CH2:34][C@@H:29]3[CH2:28]2)=[CH:23][CH:22]=1.[F:38]C(F)(F)C1N=C(N2C[C@@H]3[C@@H](N)CC[C@@H]3C2)C=CC=1>>[F:38][C@H:14]1[CH2:18][NH:8][C@H:9]([C:10]([NH:35][C@@H:32]2[C@@H:30]3[C@@H:29]([CH2:28][N:27]([C:24]4[CH:23]=[CH:22][C:21]([C:20]([F:19])([F:36])[F:37])=[CH:26][CH:25]=4)[CH2:31]3)[CH2:34][CH2:33]2)=[O:12])[CH2:13]1
Reactant: N[C@H]1CC[C@@H]2CN(c3ccc(C(F)(F)F)cc3)C[C@@H]21
Reactant: CN(C(=O)OC(C)(C)C)[C@@H](CC(C)(C)C)C(=O)O
Reactant: N[C@H]1CC[C@@H]2CN(c3cccc(C(F)(F)F)n3)C[C@@H]21
Product: O=C(N[C@H]1CC[C@@H]2CN(c3ccc(C(F)(F)F)cc3)C[C@@H]21)[C@@H]1C[C@@H](F)CN1

Procedure:
The title compound was prepared by substituting N-(tert-butoxycarbonyl)-trans-4-fluoro-L-proline for (S)-2-(tert-butoxycarbonyl(methyl)amino)-4,4-dimethylpentanoic acid and (3aR,4S,6aS)-2-[4-(trifluoromethyl)phenyl]octahydrocyclopenta[c]pyrrol-4-amine from Example 607 for (3aR,4S,6aS)-2-(6-(trifluoromethyl)pyridin-2-yl)octahydrocyclopenta[c]pyrrol-4-amine in the procedure described in Example 587: 1H NMR (500 MHz, pyridine-d5) δ ppm 8.32 (d, J=7.5, 1H), 7.57 (d, J=7.7, 2H), 6.60 (d, J=8.7, 2H), 5.30-5.12 (m, 1H), 4.34-4.24 (m, 2H), 3.62 (s, 1H), 3.48 (dd, J=10.2, 3.5, 1H), 3.37-3.26 (m, 2H), 3.19 (dd, J=12.2, 5.8, 1H), 3.05-2.98 (m, 1H), 2.97-2.84 (m, 1H), 2.76-2.65 (m, 1H), 2.59 (dddd, J=14.7, 10.3, 8.4, 3.9, 2H), 2.26 (dddd, J=39.3, 14.8, 7.9, 4.4, 1H), 2.10-2.02 (m, 1H), 1.92 (dtd, J=13.0, 8.0, 5.0, 1H), 1.60 (dq, J=12.6, 8.0, 1H), 1.41-1.30 (m, 1H); MS (ESI+) m/z 386 (M+H)+.
Reaction SMILES: N1C=CN=C1CN1C(=O)C[O:10][C:9]2N=C(C3C=CC(C4(N)CCC4)=CC=3)C(C3C=CC=CC=3)=CC1=2.C(OC(=O)[NH:41][C:42]1([C:46]2[CH:51]=[CH:50][C:49]([C:52]3[C:53]([C:69]4[CH:74]=[CH:73][CH:72]=[CH:71][CH:70]=4)=[CH:54][C:55]4[N:60]([CH2:61][C:62]5([CH3:66])C[O:64][CH2:63]5)[C:59](=[O:67])[CH2:58][O:57][C:56]=4[N:68]=3)=[CH:48][CH:47]=2)[CH2:45][CH2:44][CH2:43]1)(C)(C)C>>[NH2:41][C:42]1([C:46]2[CH:47]=[CH:48][C:49]([C:52]3[C:53]([C:69]4[CH:70]=[CH:71][CH:72]=[CH:73][CH:74]=4)=[CH:54][C:55]4[N:60]([CH2:61][C:62]([CH2:9][OH:10])([CH3:66])[CH2:63][OH:64])[C:59](=[O:67])[CH2:58][O:57][C:56]=4[N:68]=3)=[CH:50][CH:51]=2)[CH2:45][CH2:44][CH2:43]1
Reactant: NC1(c2ccc(-c3nc4c(cc3-c3ccccc3)N(Cc3ncc[nH]3)C(=O)CO4)cc2)CCC1
Reactant: CC1(CN2C(=O)COc3nc(-c4ccc(C5(NC(=O)OC(C)(C)C)CCC5)cc4)c(-c4ccccc4)cc32)COC1
Product: CC(CO)(CO)CN1C(=O)COc2nc(-c3ccc(C4(N)CCC4)cc3)c(-c3ccccc3)cc21
Yield: 79 %

Procedure:
Following the procedure for 1-((1H-imidazol-2-yl)methyl)-6-(4-(1-aminocyclobutyl)phenyl)-7-phenyl-1H-pyrido[2,3-b][1,4]oxazin-2(3H)-one, tert-butyl(1-(4-(1-((3-methyloxetan-3-yl)methyl)-2-oxo-7-phenyl-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-6-yl)phenyl)cyclobutyl)carbamate (16 mg, 0.03 mmol) was reacted to afford the title compound (16 mg, 79%). LCMS (Method D): RT=0.721 min, M+1=474. 1H NMR (500 MHz, MeOD): 8.03 (1H,S), 7.44-7.38 (4H,m), 7.30-7.24 (5H, m), 4.96 (2H, s), 4.11 (2H, s), 3.47-3.41 (4H, m), 2.77-2.72 (2H, m), 2.59-2.53 (2H, m), 2.25-2.21 (1H, m), 1.98-1.94 (1H, m), 0.92 (3H, s).
Reaction SMILES: [C:1]1([CH:7]2[CH2:11][CH2:10][NH:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH:12]([C:14]1[CH:28]=[CH:27][C:17]([O:18][C:19]2[CH:26]=[CH:25][C:22]([C:23]#[N:24])=[CH:21][N:20]=2)=[C:16]([F:29])[CH:15]=1)=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(=O)C>ClCCCl.C(OCC)(=O)C>[F:29][C:16]1[CH:15]=[C:14]([CH2:12][N:9]2[CH2:10][CH2:11][CH:7]([C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)[CH2:8]2)[CH:28]=[CH:27][C:17]=1[O:18][C:19]1[CH:26]=[CH:25][C:22]([C:23]#[N:24])=[CH:21][N:20]=1
Reactant: N#Cc1ccc(Oc2ccc(C=O)cc2F)nc1
Reactant: c1ccc(C2CCNC2)cc1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: ClCCCl
Solvent: CCOC(C)=O
Solvent: CC(=O)O
Product: N#Cc1ccc(Oc2ccc(CN3CCC(c4ccccc4)C3)cc2F)nc1
Yield: 74.9 %

Procedure:
Using a method similar to Example 365 step 2, using 3-phenyl-pyrolidine (0.169 g, 1.15 mmol), 6-(4-formyl-2-fluoro-phenoxy)-nicotinonitrile (compound of example 375 step 1), (0.200 g, 0.826 mmol), sodium triacetoxyborohydride (0.262 g, 1.24 mmol), and acetic acid (0.071 mL, 1.24 mmol) in 1,2-dichloroethane (8.0 mL), after silica gel chromatography (3:1 hexanes:ethyl acetate), provides 0.231 g (75%) of the title compound as a clear syrup: mass spectrum (electrospray): m/z=374.2 (M+1); 1H NMR (CDCl3): 8.40 (d, 1H, J=2.9 Hz), 7.91 (dd, 1H, J=2.4, 8.3 Hz), 7.30-7.24 (m, 2H), 7.24-7.21 (m, 3H), 7.20-7.09 (m, 3H), 7.06 (d, 1H, J=8.8 Hz), 3.70-3.61 (m, 2H), 3.40-3.31 (m, 1H), 3.01 (t, 1H, J=8.8 Hz), 2.84-2.77 (m, 1H), 2.75-2.67 (m, 1H), 2.53 (dd, 1H, J=7.8, 9.3 Hz), 2.39-2.28 (m, 1H), 1.95-1.84 (m, 1H).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([CH3:11])[N:10]=1)[C:5]([NH2:7])=O.COC(OC)[N:15]([CH3:17])C.C(O)(=O)C.[NH2:24]N>CN(C=O)C.C(O)(=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([C:5]2[N:15]=[CH:17][NH:24][N:7]=2)[CH:8]=[C:9]([CH3:11])[N:10]=1
Reactant: NN
Reactant: COC(OC)N(C)C
Reactant: Cc1cc(C(N)=O)cc(Cl)n1
Solvent: CC(=O)O
Solvent: CN(C)C=O
Product: Cc1cc(-c2nc[nH]n2)cc(Cl)n1
Temperature: 90 °C
Reaction time: 1 h

Procedure:
2-Chloro-6-methyl-isonicotinamide (1.23 g) and N,N-dimethylformamide dimethyl acetal (1.05 ml) were dissolved in dry DMF (4 ml) under inert atmosphere and the resulting solution was heated to 90° C. and stirred for 1 h. The reaction mixture was cooled to room temperature and a solution of hydrazine acetate (3.32 g) in acetic acid (8 ml) was dropwise added. The mixture was heated to 90° C. and stirred for 1 h. The solvent was removed under reduced pressure and the residue partitioned between saturated aqueous solution of NaHCO3 and EtOAc. The organic phase was separated, washed with brine, dried under Na2SO4, filtered and the solvent was evaporated under reduced pressure. The crude was purified by flash column chromatography (10 g Isolute® silica gel cartridge; gradient elution: hexane/EtOAc from 1/1 to 3/7) affording 2-Chloro-6-methyl-4-(1H-[1,2,4]triazol-3-yl)-pyridine (0.92 g). GC (Rt)=13.21 min (method=3A)
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][CH2:16][CH2:17]I)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:19]([NH:22][CH2:23][CH2:24][CH3:25])[CH2:20][CH3:21].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.O>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][CH2:16][CH2:17][N:22]([CH2:23][CH2:24][CH3:25])[CH2:19][CH2:20][CH3:21])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CCCNCCC
Reactant: ICCCc1ccc(OCc2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: CCCN(CCC)CCCc1ccc(OCc2ccccc2)cc1
Temperature: 25 °C
Reaction time: 29 h

Procedure:
To a solution of 3-(4-benzyloxyphenyl)propyl iodide (1.790 g) in DMF (20 ml) were added N,N-dipropylamine (1.3 ml) and potassium carbonate (1.391 g). The reaction mixture was stirred at room temperature for 29 hr, diluted with water, and extracted with ethyl acetate. The residue was purified by silica gel column chromatography (eluent:hexane/ethyl acetate=1/1) to obtain 3-(4-benzyloxyphenyl)propyl-N,N-dipropylamine (1.589 g).
Reaction SMILES: C([Mg]Cl)(C)(C)C.[Cl:7][C:8]1[CH:18]=[CH:17][CH:16]=[C:15]([Si:19]([CH3:22])([CH3:21])[CH3:20])[C:9]=1[C:10]([NH:12][CH2:13][CH3:14])=[O:11].[CH3:23][O:24][CH2:25]Cl>C1COCC1>[Cl:7][C:8]1[CH:18]=[CH:17][CH:16]=[C:15]([Si:19]([CH3:21])([CH3:20])[CH3:22])[C:9]=1[C:10]([N:12]([CH2:13][CH3:14])[CH2:23][O:24][CH3:25])=[O:11]
Reactant: CCNC(=O)c1c(Cl)cccc1[Si](C)(C)C
Reactant: COCCl
Agent: CC(C)(C)[Mg]Cl
Solvent: C1CCOC1
Product: CCN(COC)C(=O)c1c(Cl)cccc1[Si](C)(C)C
Temperature: 25 °C
Reaction time: 1 h
Yield: 53.4 %

Procedure:
A 2M THF solution of tert-butylmagnesium chloride (2.5 mL, 5 mmol) was added to an ice water cooled solution of the compound of Example 45 (1.28 g, 5 mmol) in THF (25 mL). Chloromethyl methyl ether (0.44 g, 5.5 mmol) was then added and the reaction mixture was stirred at ambient temperature for 1 h and then partitioned between water and ethyl acetate. The organic solution was dried (MgSO4), concentrated, and purified by RC with 1:9 ethyl acetate/hexanes to afford 0.80 g of the title compound as a colorless oil, a 53% yield.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([N:8]2[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]2)[CH:5]=[CH:6][CH:7]=1.[CH3:21][N:22](C=O)C>C(OCC)(=O)C.[C-]#N.[Zn+2].[C-]#N.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>[C:21]([C:2]1[CH:3]=[C:4]([N:8]2[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]2)[CH:5]=[CH:6][CH:7]=1)#[N:22]
Reactant: CC(C)(C)OC(=O)N1CCN(c2cccc(Br)c2)CC1
Reactant: CN(C)C=O
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [C-]#N
Agent: [Zn+2]
Solvent: CCOC(C)=O
Product: CC(C)(C)OC(=O)N1CCN(c2cccc(C#N)c2)CC1
Temperature: 80 °C
Reaction time: 12 h
Yield: 80 %

Procedure:
A suspension of 1,1-dimethylethyl 4-(3-bromophenyl)piperazine-1-carboxylate obtained in Reference Example 112 (3.10 g, 9.09 mmol), zinc cyanide (0.587 g, 5.00 mmol) and tetrakis(triphenylphosphine)palladium (0.525 g, 0.454 mmol) in DMF (30 mL) was stirred at 80° C. for 12 hr under nitrogen atmosphere. The reaction mixture was diluted with ethyl acetate, washed with water and saturated brine, and dried over sodium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel chromatography (25%-40% ethyl acetate/hexane), and crystallized from hexane to give the title compound as a white powder (2.10 g, 80%).
Reaction SMILES: [Si:1]([O:8][C@@H:9]1[C@@:26]2([CH3:27])[C:13](=[CH:14][CH:15]=[C:16]3[C@@H:25]2[CH2:24][CH2:23][C@@:21]2([CH3:22])[C@H:17]3[CH2:18][CH:19]=[C:20]2[CH2:28][OH:29])[CH2:12][C@@H:11]([O:30][Si:31]([C:34]([CH3:37])([CH3:36])[CH3:35])([CH3:33])[CH3:32])[CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[H-].[Na+].C1OCCOCCOCCOCCOC1.Br[CH2:56][CH2:57][CH2:58][C:59]([CH3:69])([O:61][Si:62]([CH2:67][CH3:68])([CH2:65][CH3:66])[CH2:63][CH3:64])[CH3:60]>O1CCCC1.C(OCC)(=O)C.O>[Si:1]([O:8][C@@H:9]1[C@@:26]2([CH3:27])[C:13](=[CH:14][CH:15]=[C:16]3[C@@H:25]2[CH2:24][CH2:23][C@@:21]2([CH3:22])[C@H:17]3[CH2:18][CH:19]=[C:20]2[CH2:28][O:29][CH2:56][CH2:57][CH2:58][C:59]([O:61][Si:62]([CH2:67][CH3:68])([CH2:63][CH3:64])[CH2:65][CH3:66])([CH3:60])[CH3:69])[CH2:12][C@@H:11]([O:30][Si:31]([C:34]([CH3:37])([CH3:36])[CH3:35])([CH3:32])[CH3:33])[CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]
Reactant: CC[Si](CC)(CC)OC(C)(C)CCCBr
Reactant: CC(C)(C)[Si](C)(C)O[C@@H]1CC2=CC=C3[C@H](CC[C@]4(C)C(CO)=CC[C@@H]34)[C@@]2(C)[C@@H](O[Si](C)(C)C(C)(C)C)C1
Agent: C1COCCOCCOCCOCCO1
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: CC[Si](CC)(CC)OC(C)(C)CCCOCC1=CC[C@H]2C3=CC=C4C[C@@H](O[Si](C)(C)C(C)(C)C)C[C@H](O[Si](C)(C)C(C)(C)C)[C@]4(C)[C@H]3CC[C@]12C
Yield: 100 %

Procedure:
To a solution of 1α,3β-bis(tert-butyldimethylsilyloxy)-17-(hydroxymethyl)androsta-5,7,16-triene (200 mg, 0.367 mmol), sodium hydride (60% in oil, 45 mg, 1.125 mmol) and 15-crown-5 (80 mg, 0.363 mmol) in tetrahydrofuran (1 ml), was added 1-bromo-4-methyl-4-(triethylsilyloxy)pentane (220 mg, 0.745 mmol) at room temperature, followed by reflux under heating for 1 hour. The reaction solution was diluted with ethyl acetate, followed by the dropwise addition of water under cooling with ice and washing with saturated brine. The organic layer was dried over anhydrous magnesium sulfate. After distilling off the solvent under reduced pressure, the thus obtained residue was purified by column chromatography (hexane:ethyl acetate=15:1) to give the titled compound (278.7 mg, quant.) as a colorless oil.