Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([O:3][C:4]([N:6]1[C:15]2[C:10](=[CH:11][C:12]([OH:18])=[C:13]([O:16][CH3:17])[CH:14]=2)[C@H:9]([N:19]([CH2:24][C:25]2[CH:30]=[C:29]([C:31]([F:34])([F:33])[F:32])[CH:28]=[C:27]([C:35]([F:38])([F:37])[F:36])[CH:26]=2)[C:20]([O:22][CH3:23])=[O:21])[CH2:8][C@@H:7]1[CH3:39])=[O:5])[CH3:2].[C:40]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C[CH:41]=1.C(O)C.CN1CCNCC1NC(N=NC(NC1CNCCN1C)=O)=O>C1C=CC=CC=1>[CH2:1]([O:3][C:4]([N:6]1[C:15]2[C:10](=[CH:11][C:12]([O:18][CH2:40][CH3:41])=[C:13]([O:16][CH3:17])[CH:14]=2)[C@H:9]([N:19]([CH2:24][C:25]2[CH:26]=[C:27]([C:35]([F:36])([F:38])[F:37])[CH:28]=[C:29]([C:31]([F:32])([F:33])[F:34])[CH:30]=2)[C:20]([O:22][CH3:23])=[O:21])[CH2:8][C@@H:7]1[CH3:39])=[O:5])[CH3:2]
Reactant: CCOC(=O)N1c2cc(OC)c(O)cc2[C@H](N(Cc2cc(C(F)(F)F)cc(C(F)(F)F)c2)C(=O)OC)C[C@@H]1C
Reactant: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Agent: CN1CCNCC1NC(=O)N=NC(=O)NC1CNCCN1C
Solvent: c1ccccc1
Solvent: CCO
Product: CCOC(=O)N1c2cc(OC)c(OCC)cc2[C@H](N(Cc2cc(C(F)(F)F)cc(C(F)(F)F)c2)C(=O)OC)C[C@@H]1C
Yield: 63.7 %

Procedure:
A solution of cis-4-[(3,5-bis-trifluoromethyl-benzyl)-methoxycarbonyl-amino]-6-hydroxy-7-methoxy-2-methyl-3,4-dihydro-2H-quinoline-1-carboxylic acid ethyl ester (30 mg, 0.053 mmol), triphenylphosphine (28 mg, 0.11 mmol), ethanol (16 μL, 0.79 mmol), and bis-(N-methylpiperazinyl)-azodicarboxamide (30 mg, 0.11 mmol) in benzene (1 mL) was stirred at room temperature for 12 hours. Purification of the solution directly by silica gel chromatography using 0-20% ethyl acetate/hexanes as eluent afforded 20 mg of the title compound (67%): MS m/z 593 (M+), 610 (M++17); 1H NMR (CDCl3) δ6.39 (C5, s, 1H), 1.17 (C2-Me, d, 3H, J=6.2 Hz).
Reaction SMILES: [Cl-].[NH4+].O.[CH2:4]([N:11]([C:16]1[C:21]([N+:22]([O-])=O)=[CH:20][CH:19]=[C:18]([Br:25])[N:17]=1)[CH2:12][C@H:13]([OH:15])[CH3:14])[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1>C(O)C.[Fe]>[NH2:22][C:21]1[C:16]([N:11]([CH2:4][C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH2:12][C@H:13]([OH:15])[CH3:14])=[N:17][C:18]([Br:25])=[CH:19][CH:20]=1
Reactant: C[C@@H](O)CN(Cc1ccccc1)c1nc(Br)ccc1[N+](=O)[O-]
Agent: [Fe]
Agent: [Cl-]
Agent: [NH4+]
Solvent: CCO
Solvent: O
Product: C[C@@H](O)CN(Cc1ccccc1)c1nc(Br)ccc1N
Temperature: 80 °C
Reaction time: 1.5 h
Yield: 80.5 %

Procedure:
A 100-mL round bottomed flask equipped with a magnetic stir bar was charged with ammonium chloride (0.044 g, 0.820 mmol), water (8.2 mL), iron powder (4.58 g, 82 mmol), and ethanol (21.8 mL). The mixture was heated to 80° C., and a solution of (R)-1-(benzyl(6-bromo-3-nitropyridin-2-yl)amino)propan-2-ol (3.00 g, 8.2 mmol) in ethanol (8.20 mL) was slowly added over 2 min. The reaction mixture was stirred at 80° C. After 90 min, heating was discontinued and the reaction mixture filtered through a pad of Celite. The flask and Celite pad were rinsed with ethanol. The filtrate was concentrated. The residue was then partitioned between ethyl acetate and saturated aqueous sodium bicarbonate solution (20 mL). The ethyl acetate layer was washed with 5% aqueous sodium chloride solution (20 mL) and concentrated under reduced pressure to afford crude (R)-1-((3-amino-6-bromopyridin-2-yl)(benzyl)amino)propan-2-ol (2.22 g) as a dark syrup. MS (ESI, pos. ion) m/z 336, 338 [M+1]+.
Reaction SMILES: [OH:1][N:2]1[C:6](=[O:7])[C:5]2=[CH:8][CH:9]=[CH:10][CH:11]=[C:4]2[C:3]1=[O:12].C(N(CC)CC)C.[N+:20]([C:23]1[CH:24]=[CH:25][C:26]2[N:32]3[C:33]([CH2:36]Cl)=[N:34][N:35]=[C:31]3[CH2:30][N:29]=[C:28]([C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=3[Cl:44])[C:27]=2[CH:45]=1)([O-:22])=[O:21]>CC(N(C)C)=O>[N+:20]([C:23]1[CH:24]=[CH:25][C:26]2[N:32]3[C:33]([CH2:36][O:1][N:2]4[C:3](=[O:12])[C:4]5=[CH:11][CH:10]=[CH:9][CH:8]=[C:5]5[C:6]4=[O:7])=[N:34][N:35]=[C:31]3[CH2:30][N:29]=[C:28]([C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=3[Cl:44])[C:27]=2[CH:45]=1)([O-:22])=[O:21]
Reactant: O=C1c2ccccc2C(=O)N1O
Reactant: O=[N+]([O-])c1ccc2c(c1)C(c1ccccc1Cl)=NCc1nnc(CCl)n1-2
Solvent: CC(=O)N(C)C
Solvent: CCN(CC)CC
Product: O=C1c2ccccc2C(=O)N1OCc1nnc2n1-c1ccc([N+](=O)[O-])cc1C(c1ccccc1Cl)=NC2

Procedure:
In the manner given in Example 1, N-hydroxyphthalimide and triethylamine in dimethylacetamide is treated with 8-nitro-6-(o-chlorophenyl)- 1-(chloromethyl)-4H-s-triazolo[4,3-a][1,4]benzodiazepine to give 8-nitro-6-(o-chlorophenyl)-1-[(phthalimidooxy)methyl]-4H-s-triazolo[4,3-a][1,4]benzodiazepine.
Reaction SMILES: [CH3:1][N:2]1[C:6]2[CH:7]=[CH:8][C:9]([C:11](=[O:15])[C:12](=[CH2:14])[CH3:13])=[CH:10][C:5]=2[O:4][C:3]1=[O:16].[CH3:17][O:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=1[N:25]1[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]1>CC(C)=O>[CH3:1][N:2]1[C:6]2[CH:7]=[CH:8][C:9]([C:11](=[O:15])[CH:12]([CH3:13])[CH2:14][N:28]3[CH2:27][CH2:26][N:25]([C:20]4[CH:21]=[CH:22][CH:23]=[CH:24][C:19]=4[O:18][CH3:17])[CH2:30][CH2:29]3)=[CH:10][C:5]=2[O:4][C:3]1=[O:16]
Reactant: C=C(C)C(=O)c1ccc2c(c1)oc(=O)n2C
Reactant: COc1ccccc1N1CCNCC1
Solvent: CC(C)=O
Product: COc1ccccc1N1CCN(CC(C)C(=O)c2ccc3c(c2)oc(=O)n3C)CC1

Procedure:
100 cm3 of anhydrous acetone, 0.01 mole of 3-methyl-6-(2-methylenepropionyl)benzoxazolinone and 0.01 mole of 1-(2-methoxyphenyl)piperazine are introduced successively into a 250-cm3 ground-necked flask equipped with a reflux condenser and a magnetic stirrer. The mixture is brought to reflux for 6 hours and allowed to cool. The product is drained: the product of the title is obtained.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[C:10](=O)[CH3:11])([O-:3])=[O:2].O.[NH2:14][NH2:15].O>C(O)C>[N+:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[C:10](=[N:14][NH2:15])[CH3:11])([O-:3])=[O:2]
Reactant: NN
Reactant: CC(=O)c1ccccc1[N+](=O)[O-]
Solvent: O
Solvent: CCO
Product: CC(=NN)c1ccccc1[N+](=O)[O-]
Temperature: 70 °C
Reaction time: 120 h
Yield: 46.9 %

Procedure:
To a solution of 2′-nitroacetophenone (8.26 g, 50.00 mmol) in ethanol (50 ml) was added hydrazine monohydrate (4.85 ml, 100 mmol) and the reaction mixture was heated at 70° C. for 5 h. The reaction mixture was cooled to room temperature and water (100 ml) was added. After 5 d, the reaction mixture was concentrated in vacuo to ca. 100 ml and diethyl ether (100 ml) was added. The layers were separated and the aqueous layer was extracted with diethyl ether (100 ml). The combined extracts were dried (Na2SO4) and concentrated in vacuo to afford ca. 8.0 g of a crude yellow oil. This was purified by chromatography in two batches using a Biotage Flash 40M™ cartridge packed with silica gel (90 g) eluting with dichloromethane: diethyl ether (19:1) to afford the title compound as viscous yellow oil (4.20 g, 45%).
Reaction SMILES: [C:1]([CH:6]1[C:11](=[O:12])[CH2:10][CH:9]([C:13]2[CH:18]=[CH:17][C:16]([CH2:19][CH3:20])=[CH:15][CH:14]=2)[CH2:8][C:7]1=[O:21])(=O)[CH2:2][CH2:3][CH3:4].[CH2:22]([O:24][NH2:25])[CH3:23]>C(O)C>[CH2:22]([O:24][NH:25][CH2:4][CH2:3][CH2:2][CH:1]=[C:6]1[C:11](=[O:12])[CH2:10][CH:9]([C:13]2[CH:18]=[CH:17][C:16]([CH2:19][CH3:20])=[CH:15][CH:14]=2)[CH2:8][C:7]1=[O:21])[CH3:23]
Reactant: CCON
Reactant: CCCC(=O)C1C(=O)CC(c2ccc(CC)cc2)CC1=O
Solvent: CCO
Product: CCONCCCC=C1C(=O)CC(c2ccc(CC)cc2)CC1=O

Procedure:
28.6 parts by weight of 2-butyryl-5-(4-ethylphenyl)-cyclohexane-1,3-dione and 6.1 parts by weight of ethoxyamine are stirred in 150 parts by volume of ethanol at room temperature for 8 hours. The mixture is concentrated under reduced pressure, the residue is taken up in 200 parts by volume of methylene chloride and the solution is washed with 5% strength aqueous hydrochloric acid and water dried over sodium sulfate and concentrated under reduced pressure. 2-(Ethoxyaminobutylidene)-5-(4-ethylphenyl)-cyclohexane-1,3-dione is obtained as an oil (active ingredient No. 3).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH2:29][C:30](O)=[O:31])[CH:5]=[CH:6][C:7]=1[CH2:8][O:9][CH2:10][C@@H:11]1[CH2:13][C@@H:12]1[CH:14]1[CH2:19][CH2:18][N:17]([C:20]2[N:25]=[CH:24][C:23]([CH2:26][O:27][CH3:28])=[CH:22][N:21]=2)[CH2:16][CH2:15]1.O.O[N:35]1[C:39]2C=CC=[CH:43][C:38]=2N=N1.Cl.C(/N=N/CCCN(C)C)C.N1CCC1>C(Cl)Cl>[N:35]1([C:30](=[O:31])[CH2:29][C:4]2[CH:5]=[CH:6][C:7]([CH2:8][O:9][CH2:10][C@@H:11]3[CH2:13][C@@H:12]3[CH:14]3[CH2:15][CH2:16][N:17]([C:20]4[N:21]=[CH:22][C:23]([CH2:26][O:27][CH3:28])=[CH:24][N:25]=4)[CH2:18][CH2:19]3)=[C:2]([F:1])[CH:3]=2)[CH2:43][CH2:38][CH2:39]1
Reactant: COCc1cnc(N2CCC([C@H]3C[C@H]3COCc3ccc(CC(=O)O)cc3F)CC2)nc1
Reactant: On1nnc2ccccc21
Agent: C1CNC1
Agent: CC/N=N/CCCN(C)C
Agent: Cl
Solvent: ClCCl
Solvent: O
Product: COCc1cnc(N2CCC([C@H]3C[C@H]3COCc3ccc(CC(=O)N4CCC4)cc3F)CC2)nc1
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 76.3 %

Procedure:
2-(3-Fluoro-4-((((1R,2R)-2-(1-(5-(methoxymethyl)pyrimidin-2-yl)piperidin-4-yl)cyclopropyl)methoxy)methyl)phenyl)acetic acid (Step D product, 70 mg, 0.158 mmol), 1-HYDROXYBENZOTRIAZOLE HYDRATE (36.3 mg, 0.237 mmol) and (E)-3-(ETHYLDIAZENYL)-N,N-DIMETHYLPROPAN-1-AMINE HYDROCHLORIDE (42.5 mg, 0.237 mmol) were dissolved in CH2Cl2 (3 ml). The mixture was stirred at RT for 10 min., to which was added AZETIDINE (0.016 ml, 0.237 mmol). The reaction mixture was stirred at RT overnight. TLC and LC-MS showed the SM was completely consumed. The mixture was diluted with DCM, washed with water, dried over MgSO4, and evaporated to dryness. The crude product was purified by prep TLC (pure EtOAc) to afford 58.2 mg (76%) of the title compound. 1H NMR (500 MHz, CDCl3) δ 8.30 (S, 2H), 7.38 (m, 1H), 7.05 (m, 2H), 4.70 (m, 2H), 4.60-4.50 (m, 2H), 4.25 (s, 2H), 4.10˜4.00 (m, 4H), 3.70 (m, 1H), 3.40 (m, 3H), 3.32 (s, 3H), 2.83 (m, 2H), 2.25 (m, 2H), 2.05 (m, 2H), 1.82 (m, 1H), 1.40-1.20 (m, 3H), 1.05 (m, 1H), 0.70 (m, 2H), 0.40 (m, 1H). LC/MS (m/z): 483 (M+H)+, GPR119 Human EC50: 5.16 nM.
Reaction SMILES: [O-]S(C(F)(F)F)(=O)=O.[Yb+3].[O-]S(C(F)(F)F)(=O)=O.[O-]S(C(F)(F)F)(=O)=O.[Cl:26][CH2:27][C:28](OC)(OC)OC.[NH2:35][C:36]1[C:37]([C:55]#[N:56])=[N:38][C:39]([C:45]2[CH:50]=[CH:49][CH:48]=[C:47]([C:51]([F:54])([F:53])[F:52])[CH:46]=2)=[CH:40][C:41]=1[NH:42][CH2:43][CH3:44]>C(#N)C>[Cl:26][CH2:27][C:28]1[N:42]([CH2:43][CH3:44])[C:41]2[CH:40]=[C:39]([C:45]3[CH:50]=[CH:49][CH:48]=[C:47]([C:51]([F:54])([F:52])[F:53])[CH:46]=3)[N:38]=[C:37]([C:55]#[N:56])[C:36]=2[N:35]=1
Reactant: CCNc1cc(-c2cccc(C(F)(F)F)c2)nc(C#N)c1N
Reactant: COC(CCl)(OC)OC
Agent: O=S(=O)([O-])C(F)(F)F
Agent: [Yb+3]
Solvent: CC#N
Product: CCn1c(CCl)nc2c(C#N)nc(-c3cccc(C(F)(F)F)c3)cc21
Yield: 86.8 %

Procedure:
Ytterbium triflate (1.16 g, 1.8 mmol) and 2-chloro-1,1,1-trimethoxyethane (7.56 mL, 56.0 mmol) was added to a solution of 3-amino-4-ethylamino-6-(3-trifluoromethylphenyl)-pyridine-2-carbonitrile (5.73 g, 18.7 mmol) in acetonitrile (150 mL). The mixture was refluxed for 48 hours, then concentrated under reduced pressure. The residue was partitioned between ethyl acetate and water. The organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was triturated with diethyl ether, filtered off to afford the title compound (5.92 g, 87%) as a solid. 1H NMR (DMSO-d6) δ: 8.85 (s, 1H); 8.50-8.00 (m, 2H); 7.90-7.70 (m, 2H); 5.26 (s, 2H); 4,55-4.45 (m, 2H); 1.48 (t, J=7 Hz, 3H). MS m/z: 365 (M+1).
Reaction SMILES: [F:1][C:2]([F:39])([F:38])[C:3]1[CH:4]=[C:5]([CH:31]=[C:32]([C:34]([F:37])([F:36])[F:35])[CH:33]=1)[CH2:6][N:7]1[CH2:14][CH2:13][CH2:12][NH:11][C:10]2[N:15]=[C:16](S(C)(=O)=O)[N:17]=[C:18]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=3[CH3:25])[C:9]=2[C:8]1=[O:30].[N:40]1([CH:45]2[CH2:50][CH2:49][NH:48][CH2:47][CH2:46]2)[CH2:44][CH2:43][CH2:42][CH2:41]1>>[F:1][C:2]([F:39])([F:38])[C:3]1[CH:4]=[C:5]([CH:31]=[C:32]([C:34]([F:37])([F:36])[F:35])[CH:33]=1)[CH2:6][N:7]1[CH2:14][CH2:13][CH2:12][NH:11][C:10]2[N:15]=[C:16]([N:48]3[CH2:49][CH2:50][CH:45]([N:40]4[CH2:44][CH2:43][CH2:42][CH2:41]4)[CH2:46][CH2:47]3)[N:17]=[C:18]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=3[CH3:25])[C:9]=2[C:8]1=[O:30]
Reactant: C1CCN(C2CCNCC2)C1
Reactant: Cc1ccccc1-c1nc(S(C)(=O)=O)nc2c1C(=O)N(Cc1cc(C(F)(F)F)cc(C(F)(F)F)c1)CCCN2
Product: Cc1ccccc1-c1nc(N2CCC(N3CCCC3)CC2)nc2c1C(=O)N(Cc1cc(C(F)(F)F)cc(C(F)(F)F)c1)CCCN2
Yield: 92.2 %

Procedure:
In a similar-manner to Example 1, 6-[3,5-bis(trifluoromethyl)benzyl]-5,6,7,8,9,10-hexahydro-4-(2-methylphenyl)-2-(methylsulfonyl)-5-oxopyrimido[4,5-b][1,5]diazocine (Compound of Reference Example 19; 85.9 mg) was reacted with 4-(pyrrolidine-1-yl)piperidine (27.8 mg) to obtain 6-[3,5-bis(trifluoromethyl)benzyl]-5,6,7,8,9,10-hexahydro-4-(2-methylphenyl)-5-oxo-2-[4-(pyrrolidine-1-yl)piperidine-1-yl]pyrimido[4,5-b][1,5]diazocine (89.5 mg, 92%).
Reaction SMILES: [CH2:1]([N:3]1[C:12]2[C:7](=[CH:8][C:9]([F:15])=[C:10](F)[C:11]=2[F:13])[C:6](=[O:16])[C:5]([C:17]([OH:19])=[O:18])=[CH:4]1)[CH3:2].[NH2:20][C:21]1[CH:29]=[CH:28][CH:27]=[C:26]2[C:22]=1[CH2:23][NH:24][CH2:25]2.C1CCN2C(=NCCC2)CC1>CN(C=O)C>[NH2:20][C:21]1[CH:29]=[CH:28][CH:27]=[C:26]2[C:22]=1[CH2:23][N:24]([C:10]1[C:11]([F:13])=[C:12]3[C:7]([C:6](=[O:16])[C:5]([C:17]([OH:19])=[O:18])=[CH:4][N:3]3[CH2:1][CH3:2])=[CH:8][C:9]=1[F:15])[CH2:25]2
Reactant: CCn1cc(C(=O)O)c(=O)c2cc(F)c(F)c(F)c21
Reactant: Nc1cccc2c1CNC2
Solvent: CN(C)C=O
Solvent: C1CCC2=NCCCN2CC1
Product: CCn1cc(C(=O)O)c(=O)c2cc(F)c(N3Cc4cccc(N)c4C3)c(F)c21
Yield: 41.4 %

Procedure:
136 mg of 1-ethyl-6,7,8-trifluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid, 100 mg of 4-aminoisoindoline, 114 mg of DBU, and 1.5 ml of anhydrous DMF were processed in the same manner as in Example 20 to produce 80 mg of the target compound.
Reaction SMILES: COC1C=CC(C([O:22][CH2:23][C@@H:24]([OH:51])[C@@H:25]([O:43][Si](CC)(CC)CC)[C@@H:26]([O:39]CCF)[C@H:27](N2C=C(C)C(N)=NC2=O)[CH2:28][OH:29])(C2C=CC=CC=2)C2C=CC(OC)=CC=2)=CC=1.C(OC(=O)C1C=CC=CC=1)(=[O:61])C1C=CC=CC=1>CN(C=O)C.C(OCC)(=O)C>[CH2:23]([OH:22])[C@H:24]([C@@H:25]([C@@H:26]([C@@H:27]([CH2:28][OH:29])[OH:61])[OH:39])[OH:43])[OH:51]
Reactant: O=C(OC(=O)c1ccccc1)c1ccccc1
Reactant: CC[Si](CC)(CC)O[C@@H]([C@@H](OCCF)[C@@H](CO)n1cc(C)c(N)nc1=O)[C@H](O)COC(c1ccccc1)(c1ccc(OC)cc1)c1ccc(OC)cc1
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: OC[C@@H](O)[C@H](O)[C@H](O)[C@H](O)CO
Temperature: 25 °C
Reaction time: 18 h
Yield: 434 %

Procedure:
Compound 9 (1.92 g, 2.58 mmol) was dissolved in anhydrous DMF (11.9 mL) and benzoic anhydride (0.87 g, 3.85 mmol) was added with stirring at room temperature for 18 hours. The reaction mixture was diluted with ethyl acetate (100 mL) and the resulting organic phase was washed with a saturated aqueous NaHCO3 (2×100 mL) and brine (100 mL). The ethyl acetate layer was dried over anhydrous Na2SO4 and concentrated in vacuum. The residue obtained was purified by flash silica gel column chromatography and eluted with 60% ethyl acetate in hexane to yield 6-O-(4,4′-dimethoxytrityl)-3-O-(2-fluoroethyl)-4-O-(triethylsilyl)-2-deoxy-244-N-benzoyl-5-methylcytosin-1yl)-D-altro-hexitol (2.04 g, 93.2%). In a 100 mL round bottom flask, triethylamine trihydrofluoride (2.04 mL, 12.55 mmol) was dissolved in anhydrous THF (23.2 mL). Triethylamine (0.87 mL, 6.28 mmol) was added to this solution, and the mixture was quickly poured onto 6-O-(4,4′-dimethoxytrityl)-3-O-(2-fluoroethyl)-4-O-(triethylsilyl)-2-deoxy-2-(4-N-benzoyl-5-methylcytosin-1yl)-D-altro-hexitol (2.04 g, 2.44 mmol). The resulting mixture was stirred at room temperature for 6 hours and then poured into ethyl acetate (80 mL). The organic phase was washed sequentially with water (50 mL), 5% aqueous NaHCO3 (50 mL) and brine (50 mL). The ethyl acetate layer was dried over anhydrous Na2SO4, filtered and concentrated in vacuum under reduced pressure. The residue obtained was purified by silica gel column chromatography (30% ethyl acetate in hexanes) to afford compound 10 (1.66 g, 87.94%) as a white foam. MS (ES) m/z 724.3 [M+H]+.
Reaction SMILES: [Cl:1][C:2]1[N:10]=[CH:9][N:8]=[C:7]2[C:3]=1[N:4]=[CH:5][N:6]2[C@H:11]1[C@@H:15]2[O:16][C:17]([CH3:20])([CH3:19])[O:18][C@@H:14]2[C@@H:13]([C:21]([OH:23])=O)[O:12]1.C(N1C=CN=C1)(N1C=CN=C1)=O.Cl.[CH3:37][NH:38][O:39][CH3:40].N1C=CC=CC=1>ClCCl>[CH3:40][O:39][N:38]([CH3:37])[C:21]([C@@H:13]1[C@@H:14]2[C@@H:15]([O:16][C:17]([CH3:20])([CH3:19])[O:18]2)[C@H:11]([N:6]2[CH:5]=[N:4][C:3]3[C:7]2=[N:8][CH:9]=[N:10][C:2]=3[Cl:1])[O:12]1)=[O:23]
Reactant: CC1(C)O[C@@H]2[C@H](O1)[C@@H](C(=O)O)O[C@H]2n1cnc2c(Cl)ncnc21
Reactant: CNOC
Agent: Cl
Agent: O=C(n1ccnc1)n1ccnc1
Solvent: ClCCl
Solvent: c1ccncc1
Product: CON(C)C(=O)[C@H]1O[C@@H](n2cnc3c(Cl)ncnc32)[C@@H]2OC(C)(C)O[C@@H]21
Temperature: 22 °C
Reaction time: 1 h
Yield: 65.3 %

Procedure:
(3aS,4S,6R,6aR)-6-(6-Chloro-purin-9-yl)-2,2-dimethyl-tetrahydro-furo[3,4-d][1,3]dioxole-4-carboxylic acid (35.88 g) was dissolved in dichloromethane (300 ml) and treated with 1,1′-carbonyldiimidazole (20.5 g) with ice-cooling. The solution was stirred at 22° C. for 1 h, N,O-dimethylhydroxylamine hydrochloride (12.3 g) and pyridine (15 ml) were added, and stirring was continued at 22° C. for 24 h. The solution was washed with 0.5M citric acid (250 ml) and 8% sodium bicarbonate (200 ml), dried (Na2SO4) and evaporated in vacuo. The residue was purified by flash chromatography over silica gel, eluting with ethyl acetate to afford the title compound as a colourless solid (26.4 g).
Reaction SMILES: [C:1]([C:5]1[N:6]=[C:7]([N:16]2[CH2:20][CH2:19][C:18]([F:22])([F:21])[CH2:17]2)[C:8]2[N:13]=[N:12][N:11]([CH2:14][CH3:15])[C:9]=2[N:10]=1)([CH3:4])([CH3:3])[CH3:2].C(C1N=C(N2CCC(F)(F)C2)[C:30]2[N:35]=[N:34][NH:33][C:31]=2N=1)(C)(C)C.Cl.ClCC1N(C)N=NC=1>>[C:1]([C:5]1[N:6]=[C:7]([N:16]2[CH2:20][CH2:19][C:18]([F:21])([F:22])[CH2:17]2)[C:8]2[N:13]=[N:12][N:11]([CH2:14][C:15]3[N:35]([CH3:30])[N:34]=[N:33][CH:31]=3)[C:9]=2[N:10]=1)([CH3:2])([CH3:3])[CH3:4]
Reactant: CCn1nnc2c(N3CCC(F)(F)C3)nc(C(C)(C)C)nc21
Reactant: CC(C)(C)c1nc(N2CCC(F)(F)C2)c2nn[nH]c2n1
Agent: Cl
Agent: Cn1nncc1CCl
Product: Cn1nncc1Cn1nnc2c(N3CCC(F)(F)C3)nc(C(C)(C)C)nc21

Procedure:
In analogy to the procedure described for the synthesis of 5-tert-butyl-7-(3,3-difluoropyrrolidin-1-yl)-3-ethyl-3H-[1,2,3]triazolo[4,5-d]pyrimidine (example 61), the title compound was prepared from 5-tert-butyl-7-(3,3-difluoropyrrolidin-1-yl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine and 5-(chloromethyl)-1-methyl-1H-1,2,3-triazole hydrochloride and isolated as light-yellow gum. MS(m/e): 378.3 (MH+).
Reaction SMILES: [NH2:1][C:2]1[CH:15]=[CH:14][CH:13]=[CH:12][C:3]=1[C:4]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)=[O:5].[C:16]1([CH3:26])[CH:21]=[CH:20][C:19]([S:22](Cl)(=[O:24])=[O:23])=[CH:18][CH:17]=1.Cl>N1C=CC=CC=1>[C:16]1([CH3:26])[CH:21]=[CH:20][C:19]([S:22]([NH:1][C:2]2[CH:15]=[CH:14][CH:13]=[CH:12][C:3]=2[C:4]([C:6]2[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=2)=[O:5])(=[O:24])=[O:23])=[CH:18][CH:17]=1
Reactant: Nc1ccccc1C(=O)c1ccccc1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Agent: Cl
Solvent: c1ccncc1
Product: Cc1ccc(S(=O)(=O)Nc2ccccc2C(=O)c2ccccc2)cc1
Temperature: 25 °C
Reaction time: 16 h
Yield: 82.3 %

Procedure:
To a stirred solution of 15.0 g of 2-aminobenzophenone in 7.5 cc of pyridine was added 14.5 g of p-toluenesulfonyl chloride under ice-cooling. And the resulting mixture was stirred at room temperature for 16 hours. 2N HCl was added to the reaction mixture and extracted with ethyl acetate. The extract was washed with water and dried over magnesium sulfate. The solvent was distilled off and the crude crystals thus obtained were recrystallized from isopropanol to obtain 22.0 g of compound H. Yield: 82.4%.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[OH:9].[H-].[Na+].S(O[CH2:23][CH:24]1[CH2:29][CH2:28][CH:27]=[CH:26][O:25]1)(C1C=CC(C)=CC=1)(=O)=O.C(=O)(O)[O-].[Na+]>CN(C)C=O>[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[O:9][CH2:23][CH:24]1[CH2:29][CH2:28][CH:27]=[CH:26][O:25]1
Reactant: Oc1ccc(Cl)cc1Cl
Reactant: Cc1ccc(S(=O)(=O)OCC2CCC=CO2)cc1
Agent: O=C([O-])O
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: Clc1ccc(OCC2CCC=CO2)c(Cl)c1
Yield: 76.1 %

Procedure:
A solution of 359 mg of 2,4-dichlorophenol in 3 ml of dimethylformamide was stirred with 96 mg of 55% sodium hydride at room temperature for 30 minutes. A solution of 536 mg of 2-tosyloxymethyl-3,4-dihydro-2H-pyran in 2 ml of dimethylformamide was then added, and the mixture was heated at 80°-90° C. for 2 hours. The reaction mixture was then cooled and poured onto a mixture of ice and sodium bicarbonate. The mixture was extracted with diethyl ether and the extract was dried over anhydrous potassium carbonate. After evaporation of the solvent, the residue was purified by column chromatography through silica gel eluted with a 1:2 by volume mixture of benzene and hexane, to give 394 mg of 2-(2,4-dichlorophenoxymethyl)-3,4-dihydro-2H-pyran.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6]([Cl:8])[C:5]([C:9](Cl)=[O:10])=[CH:4][N:3]=1.[F:12][C:13]([F:17])([F:16])[CH2:14][NH2:15].C(N(CC)CC)C>C(Cl)Cl>[F:12][C:13]([F:17])([F:16])[CH2:14][NH:15][C:9]([C:5]1[C:6]([Cl:8])=[N:7][C:2]([Cl:1])=[N:3][CH:4]=1)=[O:10]
Reactant: O=C(Cl)c1cnc(Cl)nc1Cl
Reactant: NCC(F)(F)F
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: O=C(NCC(F)(F)F)c1cnc(Cl)nc1Cl
Temperature: 25 °C
Reaction time: 2 h
Yield: 56.9 %

Procedure:
2,4-Dichloropyrimidine-5-carbonyl chloride (1 g, 5 mmol) was dissolved in CH2Cl2 (20 mL), 2,2,2-trifluoroethylamine (515 mg, 5 mmol) and triethylamine (1.31 mL, 9 mmol) were added. The reaction mixture was stirred at 25° C. for 2 h. The reaction mixture was purified by flash chromatography to yield a white solid (780 mg, 60%). MS: m/z=271.9 [M−H]−.
Reaction SMILES: [Si]([O:8][C@H:9]1[CH2:31][CH2:30][C@@:29]2([CH3:32])[C@@H:11]([CH2:12][CH2:13][C:14]3[C:15]4[C@:25]([CH3:33])([CH2:26][CH2:27][C:28]=32)[C@@H:18]([C@H:19]([CH3:24])[CH2:20][CH2:21][CH2:22][NH2:23])[CH2:17][CH:16]=4)[C:10]1([CH3:35])[CH3:34])(C(C)(C)C)(C)C.Cl.[CH2:37]([OH:39])[CH3:38]>N1C=CC=CC=1.C(OC(=O)C)(=O)C>[CH3:35][C:10]1([CH3:34])[C@@H:9]([OH:8])[CH2:31][CH2:30][C@@:29]2([CH3:32])[C@H:11]1[CH2:12][CH2:13][C:14]1[C:15]3[C@:25]([CH3:33])([CH2:26][CH2:27][C:28]=12)[C@@H:18]([C@H:19]([CH3:24])[CH2:20][CH2:21][CH2:22][NH:23][C:37](=[O:39])[CH3:38])[CH2:17][CH:16]=3
Reactant: C[C@H](CCCN)[C@H]1CC=C2C3=C(CC[C@@]21C)[C@@]1(C)CC[C@H](O[Si](C)(C)C(C)(C)C)C(C)(C)[C@@H]1CC3
Reactant: CCO
Agent: Cl
Solvent: c1ccncc1
Solvent: CC(=O)OC(C)=O
Product: CC(=O)NCCC[C@@H](C)[C@H]1CC=C2C3=C(CC[C@@]21C)[C@@]1(C)CC[C@H](O)C(C)(C)[C@@H]1CC3

Procedure:
3β-tert-Butyldimethylsilyloxy-4,4-dimethyl-24-amino-5α-chola-8,14-diene (0.50 g) is acetylated in a mixture of 20 ml of pyridine and 7 ml of acetic anhydride and hydrolysed with HCl/ethanol. After aqueous work-up and crystallisation from ethanol/water, the title compound (0.24 g) is isolated. Melting point: 219-221° C.
Reaction SMILES: N1C2C(=CC=CC=2)C=C1.C([N:17]1[C:29]2[C:28]([O:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35]Br)=[C:27]3[N:37](C(OC(C)(C)C)=O)[C:38]4[CH:39]=[CH:40][C:41]([Br:44])=[CH:42][C:43]=4[C:26]3=[CH:25][C:24]=2[C:23]2[C:18]1=[CH:19][CH:20]=[C:21]([Br:52])[CH:22]=2)(OC(C)(C)C)=O.[NH:53]1[CH2:58][CH2:57][O:56][CH2:55][CH2:54]1>>[Br:44][C:41]1[CH:42]=[C:43]2[C:38](=[CH:39][CH:40]=1)[NH:37][C:27]1[C:28]([O:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][N:53]3[CH2:58][CH2:57][O:56][CH2:55][CH2:54]3)=[C:29]3[NH:17][C:18]4[CH:19]=[CH:20][C:21]([Br:52])=[CH:22][C:23]=4[C:24]3=[CH:25][C:26]2=1
Reactant: CC(C)(C)OC(=O)n1c2ccc(Br)cc2c2cc3c4cc(Br)ccc4n(C(=O)OC(C)(C)C)c3c(OCCCCCBr)c21
Reactant: C1COCCN1
Agent: c1ccc2[nH]ccc2c1
Product: Brc1ccc2[nH]c3c(OCCCCCN4CCOCC4)c4[nH]c5ccc(Br)cc5c4cc3c2c1

Procedure:
The title compound was prepared in a manner analogous to Example 70 except the starting indole is 5,7-diBOC-2,10-dibromo-6-(5-bromopentyloxy)indolo[2,3-b]carbazole and the reagent is morpholine. 1H-NMR (400 MHz, acetone-d6) δ ppm 8.68 (s, 1 H), 8.32 (d, J=2.4 Hz, 2 H), 7.48-7.41 (m, 4 H), 4.34 (t, J=6.8 Hz, 2 H), 3.56 (t, J=4.8 Hz, 4 H), 2.39-2.23 (m, 6 H), 1.98-1.87 (m, 2 H), 1.60-1.44 (m, 4 H); MS (ESI) m/z 584.1 (M−H)−
Reaction SMILES: [NH:1]([C:5]1[CH:13]=[CH:12][C:8]([C:9](O)=[O:10])=[CH:7][CH:6]=1)[C:2]([NH2:4])=[NH:3].S(Cl)([Cl:16])=O>>[NH:1]([C:5]1[CH:13]=[CH:12][C:8]([C:9]([Cl:16])=[O:10])=[CH:7][CH:6]=1)[C:2]([NH2:4])=[NH:3]
Reactant: O=S(Cl)Cl
Reactant: N=C(N)Nc1ccc(C(=O)O)cc1
Product: N=C(N)Nc1ccc(C(=O)Cl)cc1

Procedure:
The antineoplastic drug shown as Compound 1 may be synthesized as follows: p-guanidinobenzoic acid is refluxed with thionyl chloride to yield the corresponding p-guanidinobenzoic acid chloride. This is then reacted with ethyl p-hydroxybenzoylacetate in the presence of a catalyst such as dimethylaminopyridine (DMAP) to yield Compound 2 of the following structure: ##STR12##