Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([C:8]1[CH:9]=[N:10][C:11]2[C:16]([C:17]=1[C:18]1[CH:19]=[C:20]([NH2:24])[CH:21]=[CH:22][CH:23]=1)=[CH:15][CH:14]=[CH:13][C:12]=2[C:25]([F:28])([F:27])[F:26])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl:29][C:30]1[CH:35]=[C:34]([CH:36]=O)[CH:33]=[C:32]([Cl:38])[N:31]=1>>[CH2:1]([C:8]1[CH:9]=[N:10][C:11]2[C:16]([C:17]=1[C:18]1[CH:19]=[C:20]([NH:24][CH2:36][C:34]3[CH:33]=[C:32]([Cl:38])[N:31]=[C:30]([Cl:29])[CH:35]=3)[CH:21]=[CH:22][CH:23]=1)=[CH:15][CH:14]=[CH:13][C:12]=2[C:25]([F:28])([F:26])[F:27])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=Cc1cc(Cl)nc(Cl)c1
Reactant: Nc1cccc(-c2c(Cc3ccccc3)cnc3c(C(F)(F)F)cccc23)c1
Product: FC(F)(F)c1cccc2c(-c3cccc(NCc4cc(Cl)nc(Cl)c4)c3)c(Cc3ccccc3)cnc12

Procedure:
This compound was prepared according to the procedure of example 66, substituting 3-(3-benzyl-8-trifluoromethyl-quinolin-4-yl)-phenylamine and 2,6-dichloro-pyridine-4-carbaldehyde. MS (ESI) m/z 535.
Reaction SMILES: [CH:1]([Mg]Br)=[CH2:2].[CH:5](=[O:16])[CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH3:15]>[Cl-].[NH4+]>[CH2:1]=[CH:2][CH:5]([OH:16])[CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH3:15]
Reactant: CCCCCCCCCCC=O
Reactant: C=C[Mg]Br
Agent: [Cl-]
Agent: [NH4+]
Product: C=CC(O)CCCCCCCCCC
Reaction time: 6 h

Procedure:
To a solution of vinyl magnesium bromide in tetrahydrofuiran (1M, 82.0 mL) at 0° C. was added a solution of undecanal i (7.00 g, 41.1 mmol) in tetrahydrofuiran (25 mnL) in about 10 min. After 6 h at 0° C., saturated ammonium chloride solution (50 mL) was added. The two layers were separated. The water layer was extracted with ether (2×50 mL). The combined organic solutions were dried over anhydrous magnesium sulfate, filtered, and concentrated. The residue was purified by flash chromatography (10% ethyl acetate in hexane) to give 7.94 g (98%) of i-a as a colorless oil: IR (neat) 3409, 3079, 1644, and 1463 cm-1 ; 1H NMR (CDCl3, 300 MHz) δ 5.80 (ddd, 1 H, J=6.3, 10.7, and 17.2 Hz, CH=CH2), 5.55 (dd, 1 H, J=17.2 and 1.4 Hz, CH=CH2), 5.05 (dd, 1 H, J=10.7 and 1.4 Hz, CH=CH2), 3.99 (q, 1 H, J=6.2 Hz, CHOH), 2.58 (br s, 1 H, OH, 1.46-1.22 [m, 18 H, C(4-12)H2 ], and 0.83 (t, J=6.4 Hz, CH2CH3); 13C NMR (CDCl3, 75.5 MHz) δ 141.61, 114.50, 73.33, 37.24, 32.12, 29.83, 29.55, 25.57, 22.87, and 14.26.
Reaction SMILES: [CH3:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH3:15])=[C:9]([O:12][CH3:13])[CH:10]=2)[CH:5]=[CH:4][N:3]=1.[Cl:16][C:17]1[CH:24]=[CH:23][CH:22]=[C:21]([Cl:25])[C:18]=1[CH:19]=O.C(OC(=O)C)(=O)C>CCOCC>[Cl:16][C:17]1[CH:24]=[CH:23][CH:22]=[C:21]([Cl:25])[C:18]=1[CH:19]=[CH:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH3:15])=[C:9]([O:12][CH3:13])[CH:10]=2)[CH:5]=[CH:4][N:3]=1
Reactant: O=Cc1c(Cl)cccc1Cl
Reactant: COc1cc2ccnc(C)c2cc1OC
Solvent: CC(=O)OC(C)=O
Solvent: CCOCC
Product: COc1cc2ccnc(C=Cc3c(Cl)cccc3Cl)c2cc1OC
Reaction time: 3 h
Yield: 78.8 %

Procedure:
A mixture of 20.4 g (0.1 mole) of 1-methyl-6,7-dimethoxyisoquinoline, 18.9 g (0.108 mole) of 2,6-dichlorobenzaldehyde and 15 ml of acetic anhydride is stirred in an oil bath of 150°-160° C. for 3 hours. The termination of the reaction is controlled by thin layer chromatography. The reaction mixture is cooled to a temperature between 5° C. and 10° C. under stirring, 30 ml of ether are added to it, the separated crystals are filtered and washed twice with cold ether. The thus-obtained raw product is recrystallized from a mixture of 600 ml of acetone and 130 ml of water, The clarified solution is stirred at a temperature between 0° C. and 5° C. for 2 hours, the separated substance is filtered, washed with 25 ml of a 6:1.3 mixture of 0° C. acetone and water and dried. Thus 28.4 g (79%) of 1-(2,6-dichlorostyryl)-6,7-dimethoxyisoquinoline are obtained.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[C:9]1[N:14]=[C:13]([NH:15][C:16]2[CH:21]=[CH:20][N:19]=[C:18]3[CH:22]=[N:23][NH:24][C:17]=23)[C:12]([CH3:25])=[CH:11][N:10]=1.[N:26]([CH2:29][CH3:30])=[C:27]=[O:28]>C(#N)C.N1C=CC=CC=1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[C:9]1[N:14]=[C:13]([NH:15][C:16]2[CH:21]=[CH:20][N:19]=[C:18]3[CH:22]=[N:23][N:24]([C:27]([NH:26][CH2:29][CH3:30])=[O:28])[C:17]=23)[C:12]([CH3:25])=[CH:11][N:10]=1
Reactant: Cc1cnc(-c2cc(F)ccc2F)nc1Nc1ccnc2cn[nH]c12
Reactant: CCN=C=O
Solvent: c1ccncc1
Solvent: CC#N
Product: CCNC(=O)n1ncc2nccc(Nc3nc(-c4cc(F)ccc4F)ncc3C)c21
Temperature: 70 °C

Procedure:
To N-(2-(2,5-Difluorophenyl)-5-methylpyrimidin-4-yl)-1H-pyrazolo[4,3-b]pyridin-7-amine (108 mg, 0.319 mmol) suspended in acetonitrile (3.2 mL) was added isocyanatoethane (125.3 μl, 1.60 mmol), 15 drops of pyridine and the mixture was heated at 70° C. overnight. The reaction was cooled to give a solid which was collected by filtration, rinsed with a acetonitrile, and dried under high vacuum to give the title compound. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.22 (3H, t, J=7.20 Hz) 2.43 (3H, s) 3.37-3.48 (2H, m) 7.36-7.51 (2H, m) 7.85 (1H, ddd, J=9.22, 5.94, 3.03 Hz) 8.47-8.57 (1H, m) 8.65 (1H, s) 9.06 (1H, d, J=5.30 Hz) 9.13 (1H, t, J=5.94 Hz) 12.07 (1H, s). MS [M+H] found 410.4.
Reaction SMILES: [CH2:1]([C@@H:8]1[NH:13][CH2:12][CH2:11][N:10]([C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[C:16]([O:22][CH:23]3[CH2:26][CH2:25][CH2:24]3)[CH:15]=2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([O:29][C:30](=O)[CH2:31][C:32]1[NH:33][N:34]=[C:35]([CH2:37][CH3:38])[N:36]=1)C>>[CH2:1]([C@H:8]1[CH2:9][N:10]([C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[C:16]([O:22][CH:23]3[CH2:26][CH2:25][CH2:24]3)[CH:15]=2)[CH2:11][CH2:12][N:13]1[C:30](=[O:29])[CH2:31][C:32]1[NH:33][N:34]=[C:35]([CH2:37][CH3:38])[N:36]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CCOC(=O)Cc1nc(CC)n[nH]1
Reactant: COc1ccc(N2CCN[C@@H](Cc3ccccc3)C2)cc1OC1CCC1
Product: CCc1n[nH]c(CC(=O)N2CCN(c3ccc(OC)c(OC4CCC4)c3)C[C@@H]2Cc2ccccc2)n1
Yield: 19 %

Procedure:
Prepared using the same procedure described in Example 275 from (S)-3-benzyl-1-(3-cyclobutyloxy-4-methoxy-phenyl)-piperazine and (5-ethyl-2H-[1,2,4]triazol-3-yl)-acetic acid ethyl ester with heating for 15 days to afford the title compound as tan solid (60 mg, 19%). LC/MS (Method B) 3.22 min, [M+1]+ 490.
Reaction SMILES: C(NC(C)C)(C)C.C([Li])CCC.[CH2:13]([SnH:17]([CH2:22][CH2:23][CH2:24][CH3:25])[CH2:18][CH2:19][CH2:20][CH3:21])[CH2:14][CH2:15][CH3:16].[C:26]([O:30][C:31]([N:33]1[CH2:37][CH2:36][C:35](=[O:38])[CH2:34]1)=[O:32])([CH3:29])([CH3:28])[CH3:27]>C1COCC1>[C:26]([O:30][C:31]([N:33]1[CH2:37][CH2:36][C:35]([OH:38])([Sn:17]([CH2:13][CH2:14][CH2:15][CH3:16])([CH2:18][CH2:19][CH2:20][CH3:21])[CH2:22][CH2:23][CH2:24][CH3:25])[CH2:34]1)=[O:32])([CH3:29])([CH3:27])[CH3:28]
Reactant: CC(C)(C)OC(=O)N1CCC(=O)C1
Reactant: CCCC[SnH](CCCC)CCCC
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CC(C)NC(C)C
Product: CCCC[Sn](CCCC)(CCCC)C1(O)CCN(C(=O)OC(C)(C)C)C1
Temperature: 0 °C
Reaction time: 0.25 h

Procedure:
Diisopropylamine (25.2 mL, 0.18 mol) in anhydrous THF (500 mL) is cooled to 0° C. and n-butyllithium (112.5 mL of a 1.6 M solution in THF, 0.18 mol) is added dropwise over 20 minutes to the cooled solution. The reaction mixture is stirred for an additional 15 minutes at 0° C. and then tri-n-butyltinhydride (48.4 mL, 0.18 mol) is added dropwise over 30 minutes. The reaction mixture is then stirred for one hour and then cooled to −78° C. N-(t-butoxycarbonyl)-3-pyrrolidone (0.15 mol) in THF (500 mL) is then added dropwise to the cooled solution over one hour. After addition is complete, the reaction is stirred for 2 hours at −78° C. and then quenched with buffer (pH 6). The mixture is extracted with ethyl acetate, the organic extracts are combined, dried over anhydrous sodium sulfate, filtered and concentrated under vacuum. The residue is purified by flash chromatrography (5% ethyl acetate/hexane to provide 1-(t-butoxycarbonyl)-3-hydroxy-3-tributylstannyl pyrrolidine.
Reaction SMILES: [OH-].[Na+].C([O:5][C:6]([C:8]1[S:9][C:10]([C:13](=[O:24])[NH:14][CH2:15][C:16]2[CH:21]=[CH:20][C:19]([Cl:22])=[C:18]([Cl:23])[CH:17]=2)=[CH:11][CH:12]=1)=[O:7])C.Cl>C(O)C.O>[Cl:23][C:18]1[CH:17]=[C:16]([CH:21]=[CH:20][C:19]=1[Cl:22])[CH2:15][NH:14][C:13]([C:10]1[S:9][C:8]([C:6]([OH:7])=[O:5])=[CH:12][CH:11]=1)=[O:24]
Reactant: CCOC(=O)c1ccc(C(=O)NCc2ccc(Cl)c(Cl)c2)s1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: O=C(O)c1ccc(C(=O)NCc2ccc(Cl)c(Cl)c2)s1
Temperature: 25 °C
Reaction time: 19 h
Yield: 83 %

Procedure:
Aqueous 1M sodium hydroxide (16.3 mL; 16.3 mmole) was added to a stirring solution of (12(a)) (1.17 g; 3.3 mmole) in ethanol (70 mL). The reaction mixture was stirred at ambient temperature for 19 hours, reduced to a small volume, diluted with water and adjusted to pH 2 by addition of 2M hydrochloric acid. The filtered solid was washed with water and dried in vacuo to give 5-(3,4-dichlorobenzyl-carbamoyl)-thiophene-2-carboxylic acid (12(b)) as a white solid (83%).
Reaction SMILES: [Br:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([OH:17])=[C:7]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH:8]=[N:9]2)=[CH:4][CH:3]=1.[C:18](=O)([O-])[O-].[K+].[K+].CI>CN(C)C=O>[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6](=[O:17])[C:7]([C:12]([O:14][CH2:15][CH3:16])=[O:13])=[CH:8][N:9]2[CH3:18])=[CH:4][CH:3]=1
Reactant: O=C([O-])[O-]
Reactant: CCOC(=O)c1cnc2cc(Br)ccc2c1O
Agent: [K+]
Solvent: CI
Solvent: CN(C)C=O
Product: CCOC(=O)c1cn(C)c2cc(Br)ccc2c1=O
Reaction time: 3 h
Yield: 86.7 %

Procedure:
A suspension of 4.04 g of ethyl 7-bromo-4-hydroxy-quinoline-3-carboxylate (J. Am. Chem. Soc. 71,3226, (1949)) and 4.71 g of potassium carbonate in 30 ml of dimethylformamide is treated with 9.68 g of methyl iodide at room temperature. The reaction mixture is heated to 90° and stirred at this temperature for 3 hrs. The reaction mixture is concentrated in a high vacuum. The residue is suspended in 50 ml of water, filtered off under suction and washed with 50 ml of water. Recrystallization of the crude product from ethanol/diethyl ether yields 3.67 g (86%) of ethyl 7-bromo-1-methyl-4-oxo-1,4-dihydro-quinoline-3-carboxylate as a colourless solid. M.p. 189°-191°.
Reaction SMILES: [OH:1][C@@H:2]([C@H:4]1[C:24](=[O:25])[N:6]2[C:7]([C:21]([O-:23])=[O:22])=[C:8]([S:11]/[CH:12]=[CH:13]\[C:14]3[S:18][CH:17]=[N:16][C:15]=3[CH2:19][OH:20])[C@H:9]([CH3:10])[C@H:5]12)[CH3:3].[Na+].[CH2:27]([O:32][C:33]([O:35][CH2:36]I)=[O:34])[C:28]([CH3:31])([CH3:30])[CH3:29]>>[OH:1][C@@H:2]([C@H:4]1[C:24](=[O:25])[N:6]2[C:7]([C:21]([O:23][CH2:36][O:35][C:33]([O:32][CH2:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:34])=[O:22])=[C:8]([S:11]/[CH:12]=[CH:13]\[C:14]3[S:18][CH:17]=[N:16][C:15]=3[CH2:19][OH:20])[C@H:9]([CH3:10])[C@H:5]12)[CH3:3]
Reactant: C[C@@H](O)[C@H]1C(=O)N2C(C(=O)[O-])=C(S/C=C\c3scnc3CO)[C@H](C)[C@H]12
Reactant: CC(C)(C)COC(=O)OCI
Agent: [Na+]
Product: C[C@@H](O)[C@H]1C(=O)N2C(C(=O)OCOC(=O)OCC(C)(C)C)=C(S/C=C\c3scnc3CO)[C@H](C)[C@H]12
Yield: 92.6 %

Procedure:
In the same manner as in Example 81, 193 mg of the title compound was prepared from 160 mg of sodium (1R,5S,6S)-6-((1R)-1-hydroxyethyl)-2-[[(Z)-2-(4-hydroxymethylthiazol-5-yl)ethen-1-yl]thio]-1-methyl-1-carbapen-2-em-3-carboxylate and 129 mg of neopentyloxycarbonyloxymethyl iodide.
Reaction SMILES: [C:1]([N:11]1[CH2:16][CH2:15][N:14]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=2[N+:23]([O-])=O)[CH:13]([C:26]([OH:28])=O)[CH2:12]1)([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=O.[OH-:29].[Na+].S(S([O-])=O)([O-])=O.[Na+].[Na+].Cl>O>[C:1]([N:11]1[CH2:16][CH2:15][N:14]2[C:17]3[C:18]([NH:23][C:26](=[O:28])[CH:13]2[CH2:12]1)=[CH:19][CH:20]=[CH:21][CH:22]=3)([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:29]
Reactant: [OH-]
Reactant: O=C(O)C1CN(C(=O)OCc2ccccc2)CCN1c1ccccc1[N+](=O)[O-]
Agent: Cl
Agent: O=S([O-])S(=O)[O-]
Agent: [Na+]
Solvent: O
Product: O=C1Nc2ccccc2N2CCN(C(=O)OCc3ccccc3)CC12
Reaction time: 2.5 h

Procedure:
To a solution of 13 g. of 4-carbobenzoxy-1-(o-nitrophenyl)piperazine-2-carboxylic acid and 11.0 g. of sodium hydroxide in 200 ml. of water is added a solution of 20 g. of sodium hydrosulfite in 200 ml. of H2O. The orange solution gradually turns colorless over a period of 2-3 hours. Dilute hydrochloric acid is added to bring the pH of the solution to about 3. A white precipitate forms. Stirring is continued for about 3-5 minutes, and the pH is raised to about 7 by the addition of 40% sodium hydroxide. Filtration gives 8.6 g. of product, m.p. 125°-140°. The analytical sample on recrystallization from ethyl acetate hexane gave a m.p. 167°-170°.
Reaction SMILES: C([O:5][C:6]([C:8]1[CH:9]=[C:10]2[C:23](=[CH:24][CH:25]=1)[C@@H:22]1[C@H:13]([C@H:14]3[C@@:18]([CH2:20][CH2:21]1)([CH3:19])[C:17]([F:27])([F:26])[CH2:16][C@@H:15]3[CH2:28][CH2:29][CH2:30][C:31]([N:33]1[CH2:38][CH2:37][O:36][CH2:35][CH2:34]1)=[O:32])[CH2:12][CH2:11]2)=[O:7])CCC.[Li+].[OH-].CO>O>[N:33]1([C:31](=[O:32])[CH2:30][CH2:29][CH2:28][C@@H:15]2[C@H:14]3[C@H:13]4[C@H:22]([CH2:21][CH2:20][C@:18]3([CH3:19])[C:17]([F:26])([F:27])[CH2:16]2)[C:23]2[C:10](=[CH:9][C:8]([C:6]([OH:7])=[O:5])=[CH:25][CH:24]=2)[CH2:11][CH2:12]4)[CH2:38][CH2:37][O:36][CH2:35][CH2:34]1
Reactant: CCCCOC(=O)c1ccc2c(c1)CC[C@H]1[C@@H]3[C@@H](CCCC(=O)N4CCOCC4)CC(F)(F)[C@@]3(C)CC[C@H]21
Agent: [Li+]
Agent: [OH-]
Solvent: CO
Solvent: O
Product: C[C@]12CC[C@@H]3c4ccc(C(=O)O)cc4CC[C@H]3[C@@H]1[C@@H](CCCC(=O)N1CCOCC1)CC2(F)F
Temperature: 50 °C
Reaction time: 2 h
Yield: 26.8 %

Procedure:
796 mg 15α-(4-morpholin-4-yl-4-oxobutyl)-17,17-difluoro-estra-1(10),2,4-triene-3-carboxylic acid butyl ester and 5 eq LiOH are mixed with 30 ml MeOH and 10 ml H2O and stirred at 50° C. (water bath) for about 4 h. Then a few mg LiOH, 30 ml MeOH and 10 ml H2O were added and the reaction mixture was stirred for another 2 h at 50° C. After reducing the solvents, H2O is added, the reaction mixture is extracted with EtOAc. The combined aquatic layers are acidified with KHSO4aq to pH 2-3, and extracted twice with EtOAc. The latter organic layers are combined, washed with brine, dried (Na2SO4) and the solvent removed. Purifying by column chromatography (CH2Cl2: MeOH:AcOH 37:3:0.1) give 191 mg of pure 15α-(4-morpholin-4-yl-4-oxobutyl)-17,17-difluoro-estra-1(10),2,4-triene-3-carboxylic acid (=EXAMPLE 7, for NMR see below). 15α-(4-morpholin-4-yl-4-oxobutyl)-17,17-difluoro-estra-1(10),2,4-triene-3-carboxamide
Reaction SMILES: [O:1]=[PH:2]1[O:9][C:8]2[C:10]([C:18]([CH3:21])([CH3:20])[CH3:19])=[CH:11][C:12]([C:14]([CH3:17])([CH3:16])[CH3:15])=[CH:13][C:7]=2[CH2:6][C:5]2[CH:22]=[C:23]([C:30]([CH3:33])([CH3:32])[CH3:31])[CH:24]=[C:25]([C:26]([CH3:29])([CH3:28])[CH3:27])[C:4]=2[O:3]1.Cl[P:35]1[O:42][C:41]2[C:43]([C:51]([CH3:54])([CH3:53])[CH3:52])=[CH:44][C:45]([C:47]([CH3:50])([CH3:49])[CH3:48])=[CH:46][C:40]=2[CH2:39][C:38]2[CH:55]=[C:56]([C:63]([CH3:66])([CH3:65])[CH3:64])[CH:57]=[C:58]([C:59]([CH3:62])([CH3:61])[CH3:60])[C:37]=2[O:36]1.C(N(CC)CC)C>C1(C)C=CC=CC=1>[C:14]([C:12]1[CH:11]=[C:10]([C:18]([CH3:19])([CH3:20])[CH3:21])[C:8]2[O:9][P:2]([O:1][P:35]3[O:42][C:41]4[C:43]([C:51]([CH3:52])([CH3:53])[CH3:54])=[CH:44][C:45]([C:47]([CH3:50])([CH3:48])[CH3:49])=[CH:46][C:40]=4[CH2:39][C:38]4[CH:55]=[C:56]([C:63]([CH3:66])([CH3:65])[CH3:64])[CH:57]=[C:58]([C:59]([CH3:62])([CH3:61])[CH3:60])[C:37]=4[O:36]3)[O:3][C:4]3[C:25]([C:26]([CH3:29])([CH3:28])[CH3:27])=[CH:24][C:23]([C:30]([CH3:33])([CH3:32])[CH3:31])=[CH:22][C:5]=3[CH2:6][C:7]=2[CH:13]=1)([CH3:17])([CH3:15])[CH3:16]
Reactant: CC(C)(C)c1cc2c(c(C(C)(C)C)c1)OP(Cl)Oc1c(cc(C(C)(C)C)cc1C(C)(C)C)C2
Reactant: CC(C)(C)c1cc2c(c(C(C)(C)C)c1)O[PH](=O)Oc1c(cc(C(C)(C)C)cc1C(C)(C)C)C2
Solvent: Cc1ccccc1
Solvent: CCN(CC)CC
Product: CC(C)(C)c1cc2c(c(C(C)(C)C)c1)OP(OP1Oc3c(cc(C(C)(C)C)cc3C(C)(C)C)Cc3cc(C(C)(C)C)cc(C(C)(C)C)c3O1)Oc1c(cc(C(C)(C)C)cc1C(C)(C)C)C2
Temperature: 25 °C
Reaction time: 14 h

Procedure:
To a solution of 2.0 g (4.3 mmol) of the compound of Example 5 in 150 mL of toluene is added 2.1 g (4.3 mmol) of the compound of Example 4 and 3.0 mL (22 mmol) of triethylamine at ambient temperature. The reaction mixture is stirred at room temperature for 14 hours. The solvent is removed under vacuum and the residue is recrystallized twice from acetonitrile to give the title compound as a white solid melting at 249°-252° C.
Reaction SMILES: Br[C:2]1[S:3][CH:4]=[CH:5][N:6]=1.[CH3:7][N:8]([CH3:12])[CH2:9][C:10]#[CH:11]>[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Cu]I.C(N(CC)CC)C>[CH3:7][N:8]([CH3:12])[CH2:9][C:10]#[C:11][C:2]1[S:3][CH:4]=[CH:5][N:6]=1
Reactant: Brc1nccs1
Reactant: C#CCN(C)C
Agent: Cl[Pd]Cl
Agent: [Cu]I
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CCN(CC)CC
Product: CN(C)CC#Cc1nccs1
Reaction time: 0.08 h

Procedure:
A mixture of 5.02 g of 2-bromothiazole, 20 ml of triethylamine, and 4.3 ml of 1-dimethylamino-2-propyne is stirred under argon for 5 minutes. Seven hundred and fifty milligrams of bis(triphenylphosphine) palladium (II) chloride and 0.450 mg of copper (I) iodide is added and the stirred reaction is heated at 80°-85° C. for 3 hours. The reaction mixture is cooled, partitioned between diethyl ether and 65 ml of 10% sodium carbonate, and the layers are separated. The organic layer is filtered through diatomaceous earth, washed with aqueous sodium chloride and dried over magnesium sulfate. The crude product is purified by chromatography using silica gel as absorbant followed by filtration of the product band through a pad of magnesium silicate to give 0.35 g of the desired product as an oil, MH+ 167. Purity is determined by 1H PMR spectroscopy and by thin layer chromatography.
Reaction SMILES: [ClH:1].[NH2:2][C:3]1[NH:4][CH2:5][C:6]([CH3:10])([CH3:9])[CH2:7][N:8]=1.[NH3:11]>>[ClH:1].[NH:2]([C:3]1[NH:8][CH2:7][C:6]([CH3:10])([CH3:9])[CH2:5][N:4]=1)[NH2:11]
Reactant: N
Reactant: CC1(C)CN=C(N)NC1
Agent: Cl
Product: CC1(C)CN=C(NN)NC1
Reaction time: 8 h

Procedure:
The product (2.60 parts) of Example 1 above, 2-amino-5,5-dimethyl-1,4,5,6-tetrahydropyrimidine hydrochloride, is added to a suitable flask equipped with condenser and magnetic stirring bar, and flushed with argon. There is next added 1.19 parts, 1.5 equivalents, of hydrazine hydrate, and the mixture is stirred until a clear solution is obtained. The flask is then placed in an oil bath preheated to 115° C. Ammonia is evolved almost immediately. The reaction is maintained at 115°-120° C. under a stream of argon for twelve hours. After sitting overnight at room temperature, the flask contains a white, crystalline solid and a small amount of clear, colorless liquid. The liquid is evaporated at room temperature. Resultant yield of 2-hydrazino-5,5-dimethyl-1,4,5,6-tetrahydropyrimidine hydrochloride which is found to be 97% pure is almost quantitative.
Reaction SMILES: [NH:1]([C:3]1[CH:8]=[C:7]([O:9][CH2:10][CH2:11][O:12][CH3:13])[CH:6]=[CH:5][N:4]=1)[NH2:2].[Si:14]([O:21][C:22]1[CH:23]=[CH:24][CH:25]=[C:26]2[C:31]=1[N:30]=[C:29]([CH:32]=O)[CH:28]=[CH:27]2)([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15]>CCO>[Si:14]([O:21][C:22]1[CH:23]=[CH:24][CH:25]=[C:26]2[C:31]=1[N:30]=[C:29](/[CH:32]=[N:2]/[NH:1][C:3]1[CH:8]=[C:7]([O:9][CH2:10][CH2:11][O:12][CH3:13])[CH:6]=[CH:5][N:4]=1)[CH:28]=[CH:27]2)([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:15])[CH3:16]
Reactant: CC(C)(C)[Si](C)(C)Oc1cccc2ccc(C=O)nc12
Reactant: COCCOc1ccnc(NN)c1
Solvent: CCO
Product: COCCOc1ccnc(N/N=C/c2ccc3cccc(O[Si](C)(C)C(C)(C)C)c3n2)c1
Temperature: 25 °C
Yield: 55.9 %

Procedure:
2-Hydrazinyl-4-(2-methoxyethoxy)pyridine (0.076 g, 0.415 mmol) and 8-(tert-butyldimethylsilyloxy) quinoline-2-carbaldehyde (0.119 g, 0.415 mmol) were heated to reflux in EtOH (2 mL) for 16 hours. After cooling to ambient temperature the reaction mixture was filtered and washed with EtOH to provide 105 mg (56%) of desired product as an orange solid.
Reaction SMILES: [C:1]1([B:7]([CH:9]([O:16][CH:17]([B:24]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[OH:25])[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[OH:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[N:32]1([CH2:38][CH2:39]O)[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]1>C(O)C>[C:1]1([B:7]([CH:9]([O:16][CH:17]([B:24]([C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=2)[O:25][CH2:39][CH2:38][N:32]2[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]2)[C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)[C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[O:8][CH2:39][CH2:38][N:32]2[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: OB(c1ccccc1)C(OC(B(O)c1ccccc1)c1ccccc1)c1ccccc1
Reactant: OCCN1CCCCC1
Solvent: CCO
Product: c1ccc(B(OCCN2CCCCC2)C(OC(B(OCCN2CCCCC2)c2ccccc2)c2ccccc2)c2ccccc2)cc1

Procedure:
The entitled compound (22 mg) was obtained by allowing 41 mg of bis(4,4′-(phenylhydroxyboryl)benzyl) ether and 13 mg of 1-piperidineethanol to act in 1 mL of ethanol.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([S:8][C:9]#N)=[CH:4][C:3]=1[N+:11]([O-:13])=[O:12].CN(C)C=O.[BH4-].[Na+].[F:21][C:22]([F:26])([F:25])CBr>O>[N+:11]([C:3]1[CH:4]=[C:5]([S:8][CH2:9][C:22]([F:26])([F:25])[F:21])[CH:6]=[CH:7][C:2]=1[NH2:1])([O-:13])=[O:12]
Reactant: FC(F)(F)CBr
Reactant: N#CSc1ccc(N)c([N+](=O)[O-])c1
Agent: [BH4-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: Nc1ccc(SCC(F)(F)F)cc1[N+](=O)[O-]
Temperature: 100 °C
Reaction time: 1 h

Procedure:
4.4 G. of 1-amino-2-nitro-4-thiocyanatobenzene in 10 ml. of dimethylformamide is treated under nitrogen with 0.85 g. of sodium borohydride in 10 ml. of DMF at not greater than 30° C. The mixture is stirred at 15° to 20° C for 1 hour, then treated with 5 g. of 1,1,1-trifluoro-2-bromoethane at 20° to 25° C. The mixture is heated to 100° C for 3 hours, cooled and diluted with water. The mixture is extracted with chloroform and the chloroform solution is dried over sodium sulfate. 2-Nitro-4-(2,2,2-trifluoroethylthio) aniline is obtained upon evaporation of the solution.
Reaction SMILES: C(Cl)Cl.Cl.[CH3:5][O:6][C:7]1[CH:41]=[CH:40][C:10]([CH2:11][S:12][C@@H:13]2[CH2:17][N:16]([C:18]([O:20][CH2:21][C:22]3[CH:27]=[CH:26][C:25]([N+:28]([O-:30])=[O:29])=[CH:24][CH:23]=3)=[O:19])[C@H:15]([C:31]([N:33]3[CH2:39][CH2:38][CH2:37][NH:36][CH2:35][CH2:34]3)=[O:32])[CH2:14]2)=[CH:9][CH:8]=1.[N+:42]([C:45]1[CH:58]=[CH:57][C:48]([CH2:49][O:50][C:51]([NH:53][C:54](=N)[CH3:55])=[O:52])=[CH:47][CH:46]=1)([O-:44])=[O:43]>CO>[CH3:5][O:6][C:7]1[CH:8]=[CH:9][C:10]([CH2:11][S:12][C@@H:13]2[CH2:17][N:16]([C:18]([O:20][CH2:21][C:22]3[CH:23]=[CH:24][C:25]([N+:28]([O-:30])=[O:29])=[CH:26][CH:27]=3)=[O:19])[C@H:15]([C:31]([N:33]3[CH2:39][CH2:38][CH2:37][N:36]([C:54](=[N:53][C:51]([O:50][CH2:49][C:48]4[CH:57]=[CH:58][C:45]([N+:42]([O-:44])=[O:43])=[CH:46][CH:47]=4)=[O:52])[CH3:55])[CH2:35][CH2:34]3)=[O:32])[CH2:14]2)=[CH:40][CH:41]=1
Reactant: CC(=N)NC(=O)OCc1ccc([N+](=O)[O-])cc1
Reactant: COc1ccc(CS[C@H]2C[C@@H](C(=O)N3CCCNCC3)N(C(=O)OCc3ccc([N+](=O)[O-])cc3)C2)cc1
Agent: Cl
Solvent: ClCCl
Solvent: CO
Product: COc1ccc(CS[C@H]2C[C@@H](C(=O)N3CCCN(C(C)=NC(=O)OCc4ccc([N+](=O)[O-])cc4)CC3)N(C(=O)OCc3ccc([N+](=O)[O-])cc3)C2)cc1
Yield: 14.5 %

Procedure:
25 ml of methylene chloride were added to a solution of 2.5 g of (2S,4S)-4-(4-methoxybenzylthio)-2-(1-homopiperazinylcarbonyl)-1-(4-nitrobenzyloxycarbonyl)pyrrolidine hydrochloride [prepared as described in step (i) above] in 25 ml of methanol, which was being heated under reflux, and then 904 mg of N-(4-nitrobenzyloxycarbonyl)acetamidine were added to the resulting mixture. The reaction mixture was heated under reflux for a further 5 hours, after which it was worked up and purified by the same procedure as described in Preparation 1(iii), to give 415 mg of the title compound, as a powder.