Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl.[F:2][C:3]1[CH:12]=[C:11]2[C:6]([CH2:7][CH2:8][CH2:9][CH:10]2[CH2:13][CH2:14][NH2:15])=[CH:5][CH:4]=1.[C:16](OC(=O)C)(=[O:18])[CH3:17].Cl>N1C=CC=CC=1>[F:2][C:3]1[CH:12]=[C:11]2[C:6]([CH2:7][CH2:8][CH2:9][CH:10]2[CH2:13][CH2:14][NH:15][C:16](=[O:18])[CH3:17])=[CH:5][CH:4]=1
Reactant: CC(=O)OC(C)=O
Reactant: NCCC1CCCc2ccc(F)cc21
Agent: Cl
Solvent: c1ccncc1
Product: CC(=O)NCCC1CCCc2ccc(F)cc21
Temperature: 25 °C
Reaction time: 5 h

Procedure:
1 eq. of the compound obtained in Step G is dissolved in 4 ml of pyridine and is cooled in an ice bath before adding 3 eq. of acetic anhydride dropwise. The reaction mixture is stirred for 5 hours at ambient temperature and is then poured into 3M HCl solution and extracted with ethyl ether. The organic phase is washed with 10% potassium carbonate solution and then with water, dried over MgSO4 and evaporated under reduced pressure. The oil obtained is precipitated from a mixture of ethyl ether/petroleum ether (1/2) and the precipitate formed is filtered off under suction and recrystallised.
Reaction SMILES: C([Sn](CCCC)(CCCC)[C:6]1[N:10]2[CH:11]=[CH:12][C:13]([C:15]([F:18])([F:17])[F:16])=[N:14][C:9]2=[N:8][CH:7]=1)CCC.Br[C:28]1[CH:29]=[CH:30][C:31]([C:34]2[CH:39]=[CH:38][C:37]([F:40])=[CH:36][CH:35]=2)=[N:32][CH:33]=1>>[F:40][C:37]1[CH:36]=[CH:35][C:34]([C:31]2[CH:30]=[CH:29][C:28]([C:6]3[N:10]4[CH:11]=[CH:12][C:13]([C:15]([F:16])([F:17])[F:18])=[N:14][C:9]4=[N:8][CH:7]=3)=[CH:33][N:32]=2)=[CH:39][CH:38]=1
Reactant: Fc1ccc(-c2ccc(Br)cn2)cc1
Reactant: CCCC[Sn](CCCC)(CCCC)c1cnc2nc(C(F)(F)F)ccn12
Product: Fc1ccc(-c2ccc(-c3cnc4nc(C(F)(F)F)ccn34)cn2)cc1

Procedure:
3-Tributylstannyl-7-trifluoromethylimidazo[1,2-α]pyrimidine was reacted with 5-bromo-2-(4-fluorophenyl)pyridine by the method of Example 1 to furnish 3-[2-(4-fluorophenyl)pyridin-5-yl]-7-trifluoromethylimidazo[1,2-α]pyrimidine (47mg) as a yellow solid: δH (400 MHz, CDCl3) 7.19-7.25 (2H, m), 7.31 (1H, d, J 7), 7.90-7.97 (2H, m), 8.06-8.11 (2H, m), 8.19 (1H, s), 8.82 (1H, d, J 7), 8.91 (1H, dd, J 2 and 1); m/z (ES+) 358, 359 (M++H).
Reaction SMILES: COC1C=CC(C[N:8]2[C:12]3=[N:13][CH:14]=[CH:15][C:16]([O:17][C:18]4[CH:23]=[CH:22][C:21]([NH2:24])=[CH:20][C:19]=4[F:25])=[C:11]3[C:10]([CH3:26])=[N:9]2)=CC=1.[CH3:29][N:30]1[C:35](=[O:36])[C:34]([C:37](O)=[O:38])=[CH:33][CH:32]=[N:31]1.Cl.FC1C=CC(NN)=CC=1>>[F:25][C:19]1[CH:20]=[C:21]([NH:24][C:37]([C:34]2[C:35](=[O:36])[N:30]([CH3:29])[N:31]=[CH:32][CH:33]=2)=[O:38])[CH:22]=[CH:23][C:18]=1[O:17][C:16]1[CH:15]=[CH:14][N:13]=[C:12]2[NH:8][N:9]=[C:10]([CH3:26])[C:11]=12
Reactant: COc1ccc(Cn2nc(C)c3c(Oc4ccc(N)cc4F)ccnc32)cc1
Reactant: Cn1nccc(C(=O)O)c1=O
Agent: Cl
Agent: NNc1ccc(F)cc1
Product: Cc1n[nH]c2nccc(Oc3ccc(NC(=O)c4ccnn(C)c4=O)cc3F)c12

Procedure:
Prepared by 2-step process from 3-fluoro-4-(1-(4-methoxybenzyl)-3-methyl-1H-pyrazolo[3,4-b]pyridin-4-yloxy)aniline (prepared as in Example 5, Step D) and 2-methyl-3-oxo-2,3-dihydropyridazine-4-carboxylic acid (prepared according to the 3-step procedure of Example 19, Steps A-C, substituting methylhydrazine for 1-(4-fluorophenyl)hydrazine hydrochloride) according to the procedure of Example 21, Steps A and B. The crude material was purified by silica gel flash column chromatography (3% MeOH in CH2Cl2) to afford 17 mg (64% for 2-step process) of the desired product. LRMS (ESI pos) m/e 395.2 (M+1). 1H-NMR (400 MHz, CD3OD/CDCl3) δ 8.30 (d, 1H), 8.25 (d, 1H), 8.17 (d, 1H), 8.02 (dd, 1H), 7.51 (m, 1H), 7.37 (t, 1H), 6.27 (d, 1H), 3.79 (s, 3H), 2.75 (s, 3H); 19F NMR (376 MHz, CD3OD/CDCl3) δ −128.3.
Reaction SMILES: S1C=CC2C=CC=CC1=2.Cl[C:11]1[S:15][C:14]2[CH:16]=[CH:17][CH:18]=[CH:19][C:13]=2[C:12]=1[CH3:20]>>[CH3:20][C:12]1[C:13]2[CH:19]=[CH:18][CH:17]=[CH:16][C:14]=2[S:15][CH:11]=1
Reactant: Cc1c(Cl)sc2ccccc12
Agent: c1ccc2sccc2c1
Product: Cc1csc2ccccc12

Procedure:
from benzo[b]thiophene either by chloromethylation (R. Neidlen and E.P. Mrugowski: Arch. Pharm. [Weinheim, Ger.,] 308(7), 513-9, 1975): ##STR8## or by methylation and final bromination (D.A. Shirley and M.D. Cameron: JACS, 74, 664, 1952; U.S. Pat. No. 4,282,227): ##STR9## b) from 2- chloro-3-methylbenzo[b]thiophene by bromination (European Pat. No. 54,233): ##STR10## and 2- chloro-3-methylbenzo[b]thiophene is in turn obtained by chlorination of 3- methylbenzo[b]thiophene (V.I. Dronov et al, CA, 79, 115388f): ##STR11## c) from the corresponding thiophenol by total synthesis, for example, 2- chloro-2-propenyl-phenylthioether is formed by treating 2,3- dichloropropene, transposition in N,N-diethylaniline and cyclization with concentrated hydrochloric acid (W.K. Anderson and E.J. LaVoie, J. Chem. Soc., Chem. Commun., (5), 174, 1974; W.K. Anderson et al, J. Chem. Soc., Perkin Trans. 1, (1), 1-4, 1975): ##STR12## or by an alternative process also from the corresponding thiophenol by total synthesis, for example by forming respective 2- phenylthiopropionaldehyde acetal by treatment with 2-bromopropionaldehyde in sodium ethoxide and cyclization with an admixture of polyphosphoric acid and phosphorous pentoxide (Yasuo Matsuki and Fusaji Shoji, Nippon Kagaku Zasshi, 86,(10), 1067-72. 1965): ##STR13## d) in a similar manner the 3-position compounds are also obtained from the corresponding thiophenol by total synthesis and forming respective phenylthioacetone by treatment with chloroacetone and cyclization with polyphosphoric acid (N.B. Chapman, et al, J. Chem. Soc. C., (5), pp. 512-22, 1968; N.B. Chapman, et al, ibid, (5), 2747-51, 1968): ##STR14##
Reaction SMILES: N1C2C(=CC=CC=2)CC1.[CH2:10]([N:18]1[C:26]2[C:21](=[CH:22][C:23]([C:35]([O:37]C)=[O:36])=[C:24]([CH3:34])[C:25]=2[NH:27][C:28](=[O:33])[C:29]([CH3:32])([CH3:31])[CH3:30])[CH2:20][CH2:19]1)[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH3:17].[OH-].[Na+]>CO.O>[CH2:10]([N:18]1[C:26]2[C:21](=[CH:22][C:23]([C:35]([OH:37])=[O:36])=[C:24]([CH3:34])[C:25]=2[NH:27][C:28](=[O:33])[C:29]([CH3:30])([CH3:31])[CH3:32])[CH2:20][CH2:19]1)[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH3:17]
Reactant: CCCCCCCCN1CCc2cc(C(=O)OC)c(C)c(NC(=O)C(C)(C)C)c21
Agent: [Na+]
Agent: [OH-]
Agent: c1ccc2c(c1)CCN2
Solvent: CO
Solvent: O
Product: CCCCCCCCN1CCc2cc(C(=O)O)c(C)c(NC(=O)C(C)(C)C)c21
Temperature: 60 °C
Reaction time: 4 h
Yield: 67.9 %

Procedure:
0.87 (3H, br-t, J=7 Hz, —(CH2)7CH3), 1.00-1.70 (12H, m, —CH2(CH2)6—), 1.34 (9H, s, —C(CH3)3), 2.39 (3H, s, indoline C6—CH3), 2.93 (2H, t, J=8 Hz, indoline C3—H2), 3.25 (2H, t, J=7 Hz, >NCH2—), 3.51 (2H, t, J=8 Hz, indoline C2—H2), 3.79 (3H, s, —CO2 CH3), 6.76 (1H, br, —CONH—), 7.55 (1H, s, indoline Ce—H). (6) N-(1-Octyl-5-methoxycarbonyl-6-methylindolin-7-yl)-2,2-dimethylpropanamide (580 mg) was dissolved in methanol (10 ml) and a solution of NaOH (290 mg) in water (5 ml) was added, which was followed by stirring at 60° C. for 4 hr. Methanol was evaporated under reduced pressure. Water (50 ml) was added to the residue and the mixture was washed with ethyl acetate (20 ml). The aqueous layer was adjusted to pH 6-7 with 2N sulfuric acid and extracted with chloroform (100 ml). The chloroform layer was washed with water and dried over anhydrous sodium. sulfate. Chloroform was evaporated under reduced pressure to give 380 mg of the title compound.
Reaction SMILES: Cl[C:2]1[N:3]=[CH:4][C:5](/[CH:8]=[CH:9]/[C:10]([O:12][CH3:13])=[O:11])=[N:6][CH:7]=1.[NH2:14][C@@H:15]1[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16]1.C([O-])([O-])=O.[K+].[K+]>CN1C(=O)N(C)CC1>[CH3:13][O:12][C:10](=[O:11])/[CH:9]=[CH:8]/[C:5]1[N:6]=[CH:7][C:2]([NH:14][C@@H:15]2[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16]2)=[N:3][CH:4]=1
Reactant: CC(C)(C)OC(=O)N1CC[C@@H](N)C1
Reactant: COC(=O)/C=C/c1cnc(Cl)cn1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN1CCN(C)C1=O
Product: COC(=O)/C=C/c1cnc(N[C@@H]2CCN(C(=O)OC(C)(C)C)C2)cn1
Temperature: 120 °C
Reaction time: 2 h
Yield: 69.9 %

Procedure:
To a solution of methyl (2E)-3-(5-chloro-2-pyrazinyl)acrylate (680 mg) in DMI (1.4 mL) was added tert-butyl (3R)-3-amino-1-pyrrolidinecarboxylate (957 mg) and K2CO3 (1.42 g), which was stirred at 120° C. for 2 hours. The reaction mixture was filtered and evaporated in vacuo. To the residue was added H2O, which was extracted with ethyl acetate. The organic layer was washed with brine, dried over Na2SO4, filtered, and evaporated in vacuo. The residue was purified by column chromatography on silica gel to give tert-butyl (3R)-3-({5-[(1E)-3-methoxy-3-oxo-1-propen-1-yl]-2-pyrazinyl}amino)-1-pyrrolidinecarboxylate (834 mg) as a off-white powder.
Reaction SMILES: [O:1]=[C:2]([CH2:6][CH3:7])[C:3]([OH:5])=[O:4].O.[C:9]1(C)C=CC(S(O)(=O)=O)=C[CH:10]=1>C(O)C>[CH2:9]([O:4][C:3](=[O:5])[C:2](=[O:1])[CH2:6][CH3:7])[CH3:10]
Reactant: CCC(=O)C(=O)O
Reactant: Cc1ccc(S(=O)(=O)O)cc1
Solvent: CCO
Solvent: O
Product: CCOC(=O)C(=O)CC
Temperature: 25 °C
Yield: 16662.4 %

Procedure:
2-Oxo-butyric acid (10.0 g, 97.2 mmol) was dissolved in ethanol (100 mL) and p-toluene sulfonic acid mono hydrate (0.1 g) was added. The reaction mixture was heated to reflux for 48 h. After cooling the reaction mixture to room temperature, the ethanol was removed under reduced pressure to give 11.4 g of 2-oxo-butyric acid ethyl ester.
Reaction SMILES: [Cu][C:2]#[N:3].Br[C:5]1[C:10](=[O:11])[NH:9][CH:8]=[N:7][C:6]=1[C:12]([F:15])([F:14])[F:13].C(OC(=O)C)C.Cl>N1C2C(=CC=CC=2)C=CC=1.C(O)(=O)C.O.C(O)C.C(OCC)C>[C:2]([C:5]1[C:10](=[O:11])[NH:9][CH:8]=[N:7][C:6]=1[C:12]([F:15])([F:14])[F:13])#[N:3]
Reactant: O=c1[nH]cnc(C(F)(F)F)c1Br
Reactant: N#C[Cu]
Agent: Cl
Solvent: c1ccc2ncccc2c1
Solvent: CCOCC
Solvent: CC(=O)O
Product: N#Cc1c(C(F)(F)F)nc[nH]c1=O
Temperature: 25 °C

Procedure:
Copper(I)cyanide (80 mg) was added to a solution of 5-bromo-4-trifluoromethylpyrimidin-6-one (150 mg) in quinoline (5 ml). The reaction mixture was then heated to the reflux temperature for a period of 3 hours. After cooling to the ambient temperature, the reaction mixture was pured into dilute agueous acetic acid, and extracted into ethyl acetate. After drying, evaporation of the solvent under reduced pressure gave a brown oil, which was subjected to chromatography on silica gel plates using ethylacetate containing acetic acid and water (250:5:1 by volume) as eluent. The desired fraction was collected, and the brown solid thus isolated was identified as a phenolic salt. This material was dissolved in ethanol, and acidified with ethanolic hydrogen chloride. Evaporation of the solvent under reduced pressure gave a brown solid which was dissolved in diethyl ether and filtered. Evaporation of the solvent under reduced pressure gave 5-cyano-4-trifluoromethyl-pyrimidin-6-one as a brown solid.
Reaction SMILES: [C:1]([O:9][CH3:10])(=[O:8])/[CH:2]=[CH:3]/[C:4]([O:6][CH3:7])=[O:5]>O>[CH:2]1([C:1]([O:9][CH3:10])=[O:8])[CH:3]([C:4]([O:6][CH3:7])=[O:5])[CH:2]([C:1]([O:9][CH3:10])=[O:8])[CH:3]1[C:4]([O:6][CH3:7])=[O:5]
Reactant: COC(=O)/C=C/C(=O)OC
Solvent: O
Product: COC(=O)C1C(C(=O)OC)C(C(=O)OC)C1C(=O)OC
Yield: 100 %

Procedure:
The dimethyl fumarate (1224 g, 8.5 mol) and water (4000 ml) were added to a 6-liter flask and irradiated by 365 nm ultraviolet lights at a temperature from 5 to 7° C. for 7 hours. The resultant solid in the flask was vacuum filtered to obtain tetramethyl cyclobutane-1,2,3,4-tetracarboxylate (1224 g, 4.25 mol). According to the NMR spectrum as shown in FIG. 1, dimethyl fumarate was present before the cyclization reaction. It can be observed from FIG. 2 that, after the cyclization reaction, the absorption peak at 6.77 ppm disappeared which means that dimethyl fumarate had been reacted completely. The absorption peak at 3.68 ppm represents the generation of the corresponding cyclobutanetetracarboxylate. FIGS. 1 and 2 prove that the yield of the reaction is almost 100%.
Reaction SMILES: Cl[CH:2]1[NH:7][CH2:6][CH2:5][N:4]2[C:8]([CH2:11][CH3:12])=[N:9][N:10]=[C:3]12>CO.O=[Pt]=O.[Pd]>[CH2:11]([C:8]1[N:4]2[CH2:5][CH2:6][NH:7][CH2:2][C:3]2=[N:10][N:9]=1)[CH3:12]
Reactant: CCc1nnc2n1CCNC2Cl
Agent: O=[Pt]=O
Agent: [Pd]
Solvent: CO
Product: CCc1nnc2n1CCNC2
Temperature: 25 °C
Reaction time: 16 h
Yield: 38.9 %

Procedure:
To a solution of 8-chloro-3-ethyl[1,2,4]triazolo[4,3-a]piperazine (2.24 g) in MeOH (150 mL) was added PtO2 (1.36 g) and 10% Pd/C (0.63 g) at rt. The reaction mixture was stirred under H2 for 16 h at room temperature and filtered, and the filtrate was concentrated in vacuo and the residue was chromatographed with a silica gel column to give the title compound (0.71 g, 31.17%). The compound was characterized by the following spectroscopic data: MS (ESI, pos. ion) m/z: 153.2 (M+1).
Reaction SMILES: [O:1]=[C:2]1[N:6]([CH:7]([CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[C:8]([OH:10])=[O:9])[C:5](=[S:18])[NH:4][CH2:3]1.[Br:19][C:20]1[CH:25]=[CH:24][C:23]([C:26]2[S:30][C:29]([CH:31]=O)=[CH:28][CH:27]=2)=[CH:22][C:21]=1[Cl:33].NCCC(O)=O.CO.C(Cl)Cl>C(O)(=O)C>[Br:19][C:20]1[CH:25]=[CH:24][C:23]([C:26]2[S:30][C:29](/[CH:31]=[C:3]3/[NH:4][C:5](=[S:18])[N:6]([CH:7]([CH2:11][C:12]4[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=4)[C:8]([OH:10])=[O:9])[C:2]/3=[O:1])=[CH:28][CH:27]=2)=[CH:22][C:21]=1[Cl:33]
Reactant: O=C(O)C(Cc1ccccc1)N1C(=O)CNC1=S
Reactant: O=Cc1ccc(-c2ccc(Br)c(Cl)c2)s1
Agent: NCCC(=O)O
Solvent: CO
Solvent: CC(=O)O
Solvent: ClCCl
Product: O=C(O)C(Cc1ccccc1)N1C(=O)/C(=C\c2ccc(-c3ccc(Br)c(Cl)c3)s2)NC1=S
Temperature: 170 °C

Procedure:
To a mixture of 2-(5-oxo-2-thioxoimidazolidin-1-yl)-3-phenylpropanoic acid (0.044 g, 0.175 mmol) and 5-(4-bromo-3-chloro-phenyl)thiophene-2-carbaldehyde (0.050 g, 0.166 mmol) in acetic acid 5 mL is added β-alanine (1.6 mg, 0.01 r8 mmol) and heat to 170° C. for 30 min under microwave irradiation. The resulting reaction mixture is cooled down and the solvent is removed. The pure product (0.075 g, 0.141 mmol, red solid) is obtained by column chromatography using MeOH/DCM, 2-7% ration solvent system. 1H-NMR (CDCl3/300 MHz): 9.88 (br, 1H), 8.92 (br, 1H), 7.65 (m, 2H), 7.31 (m, 8H), 6.85 (s, 1H), 5.76 (dd, J=11.1, 5.4 Hz, 1H), 3.70 (m, 2H). MS (ES−, m/z): 545.2 (M−, 100.0).
Reaction SMILES: [C:1]([C:5]1[S:9][C:8]([C:10]([O-:12])=O)=[N:7][N:6]=1)([CH3:4])([CH3:3])[CH3:2].[Li+].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:38][C:39]1[CH:40]=[C:41]([S:45]([NH2:48])(=[O:47])=[O:46])[CH:42]=[CH:43][CH:44]=1>CN(C=O)C.O>[C:1]([C:5]1[S:9][C:8]([C:10]([NH:38][C:39]2[CH:44]=[CH:43][CH:42]=[C:41]([S:45](=[O:47])(=[O:46])[NH2:48])[CH:40]=2)=[O:12])=[N:7][N:6]=1)([CH3:2])([CH3:3])[CH3:4]
Reactant: Nc1cccc(S(N)(=O)=O)c1
Reactant: CC(C)(C)c1nnc(C(=O)[O-])s1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Agent: [Li+]
Solvent: O
Solvent: CN(C)C=O
Product: CC(C)(C)c1nnc(C(=O)Nc2cccc(S(N)(=O)=O)c2)s1
Reaction time: 4 h
Yield: 31.4 %

Procedure:
A solution of lithium 5-tert-butyl-1,3,4-thiadiazole-2-carboxylate (0.2 g, 1 mmol) and HATU (0.38 g, 1.0 mmol) in DMF (5 mL) was stirred at room temperature for 10 minutes, then 3-amino-benzenesulfonamide (0. 17 g, 1.0 mmol) was added. The reaction was stirred for four hours, diluted with water, and extracted with ethyl acetate. The combined extracts were washed with brine and water, dried over sodium sulfate, and evaporated. The residue was purified by column chromatography on silica gel with 0-5% methanol in dichloromethane to give 5-tert-butyl-N-(3-sulfamoylphenyl)-1,3,4-thiadiazole-2-carboxamide (107 mg, 31% yield). LC/MS: m/z 341.1 (M+H)+ at 2.79 min (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)).
Reaction SMILES: CN.Cl[C:4]1[CH:9]=[CH:8][C:7]([S:10][C:11]([F:14])([F:13])[F:12])=[CH:6][N:5]=1.[CH3:15][N:16]1C(=O)CCC1.C(=O)([O-])[O-].[K+].[K+]>O>[CH3:15][NH:16][C:4]1[CH:9]=[CH:8][C:7]([S:10][C:11]([F:14])([F:13])[F:12])=[CH:6][N:5]=1
Reactant: FC(F)(F)Sc1ccc(Cl)nc1
Reactant: CN1CCCC1=O
Agent: CN
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Product: CNc1ccc(SC(F)(F)F)cn1
Temperature: 60 °C
Reaction time: 2 h

Procedure:
1.86 g of an aqueous methylamine solution (40%) was added dropwise to a mixture of 1.71 g of 2-chloro-5-trifluoromethylsulfanylpyridine and 16 ml of NMP, and then the mixture was heated to 60° C. and heated and stirred for 2 hours. After cooling the mixture to room temperature, 1.66 g of potassium carbonate was added, and 1.86 g of a 40% aqueous methylamine solution was added dropwise. The mixture was heated to 60° C. and further heated and stirred for 2 hours. After cooling the mixture to room temperature, water was added, and the mixture was extracted with ethyl acetate. The combined organic layer was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The resulting residue was applied to a silica gel column chromatography to obtain 1.52 g of methyl-(5-trifluoromethylsulfanylpyridin-2-yl)-amine.
Reaction SMILES: [CH2:1]([C:4]1[NH:5][C:6]2[C:7]([N:13]=1)=[N:8][CH:9]=[CH:10][C:11]=2[CH3:12])[CH2:2][CH3:3].[C:14]1([C:20]([C:46]2[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=2)([C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)[N:21]2[C:25]([C:26]3[C:31]([C:32]4[CH:37]=[CH:36][C:35]([CH2:38]Br)=[CH:34][CH:33]=4)=[CH:30][CH:29]=[CH:28][CH:27]=3)=[N:24][N:23]=[N:22]2)[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.[H-].[Na+]>>[C:46]1([C:20]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)([C:40]2[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=2)[N:21]2[C:25]([C:26]3[CH:27]=[CH:28][CH:29]=[CH:30][C:31]=3[C:32]3[CH:37]=[CH:36][C:35]([CH2:38][N:13]4[C:7]5=[N:8][CH:9]=[CH:10][C:11]([CH3:12])=[C:6]5[N:5]=[C:4]4[CH2:1][CH2:2][CH3:3])=[CH:34][CH:33]=3)=[N:24][N:23]=[N:22]2)[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1
Reactant: BrCc1ccc(-c2ccccc2-c2nnnn2C(c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Reactant: CCCc1nc2nccc(C)c2[nH]1
Agent: [H-]
Agent: [Na+]
Product: CCCc1nc2c(C)ccnc2n1Cc1ccc(-c2ccccc2-c2nnnn2C(c2ccccc2)(c2ccccc2)c2ccccc2)cc1

Procedure:
3-[2'-(N-triphenylmethyltetrazol-5-yl)biphen-4-yl]methyl-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridine was prepared according to the procedure described in Example 7, Part A from 2-propyl-7-methylimidazo[4,5-b]pyridine (991 mg, 5.66 mmol), N-triphenylmethyl-5-(4'-bromomethylbiphen-2-yl)tetrazole (3.0 g, 5.39 mmol), and NaH (6.47 mmol).
Reaction SMILES: [CH2:1](O)[CH3:2].[CH2:4]([NH2:16])[CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH3:15]>O>[CH2:4]([NH2:16])[CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:1][CH3:2]
Reactant: CCO
Reactant: CCCCCCCCCCCCN
Solvent: O
Product: CCCCCCCCCCCCCCN

Procedure:
In application Ser. No. 355,979, filed Dec. 14, 1994, describing the assembly of silica molecular sieves in 50:50 (v/v) water:ethanol, it was shown that certain alkylamine surfactants (e.g., dodecylamine) gave derivatives with high textural mesoporosity whereas others afforded relatively low textural pore volumes (e.g., tetradecylamine (Tanev, P.
Reaction SMILES: Br[C:2]1[CH:10]=[C:9]([O:11][CH3:12])[CH:8]=[C:7]2[C:3]=1[CH:4]=[CH:5][N:6]2[S:13]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)(=[O:15])=[O:14].[CH2:22]([Sn](CCCC)(CCCC)C=C)[CH2:23]CC>C1(C)C=CC=CC=1>[CH3:12][O:11][C:9]1[CH:8]=[C:7]2[C:3]([CH:4]=[CH:5][N:6]2[S:13]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)(=[O:15])=[O:14])=[C:2]([CH:22]=[CH2:23])[CH:10]=1
Reactant: COc1cc(Br)c2ccn(S(=O)(=O)c3ccccc3)c2c1
Reactant: C=C[Sn](CCCC)(CCCC)CCCC
Solvent: Cc1ccccc1
Product: C=Cc1cc(OC)cc2c1ccn2S(=O)(=O)c1ccccc1
Temperature: 110 °C
Reaction time: 16 h
Yield: 106.4 %

Procedure:
4-Bromo-6-methoxy-1-(phenylsulfonyl)-1H-indole (0.33 g, 0.9 mmol; Intermediate 32) was dissolved in dry toluene (4 mL) and tributyl(vinyl)stannane (0.53 mL, 1.8 mmol) and bis(triphenylphosphine)palladium(II)acetate (0.03 g, 0.05 mmol) were added. The mixture was stirred in STEM-block at 110° C. for 16 h. The crude product was combined with an earlier batch of this intermediate, filtrated and the solvent was evaporated. The residue was purified by flash chromatography using isohexane:dichloromethane 1:1 as eluent yielding 0.30 g (89%) of the title compound. MS (ESI+) for C17H15NO3S m/z 314 (M+H)+.
Reaction SMILES: Cl[C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][N:11]=1)[C:5]([O:7][CH3:8])=[O:6].[C:12]1([C:18]#[CH:19])[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1>[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.C(N(CC)CC)C>[C:12]1([C:18]#[C:19][C:2]2[CH:3]=[C:4]([CH:9]=[CH:10][N:11]=2)[C:5]([O:7][CH3:8])=[O:6])[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1
Reactant: C#Cc1ccccc1
Reactant: COC(=O)c1ccnc(Cl)c1
Agent: Cl[Pd]Cl
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CCN(CC)CC
Product: COC(=O)c1ccnc(C#Cc2ccccc2)c1
Temperature: 25 °C

Procedure:
Methyl 2-chloroisonicotinate, 2 (19.08 9, 0.111 mol as 100% pure), phenylacetylene (13.6 g, 0.133 mol), cuprous iodide (1.00 g,5.25 mmol) and triethylamine (30 ml) were mixed together with stirring at room temperature, and to this mixture was added bis(triphenylphosphine) palladium (II) chloride (2.0 g, 2.85 mmol).
Reaction SMILES: [CH3:1][C:2]1[NH:3][C:4]([CH3:13])=[C:5]([CH:11]=[O:12])[C:6]=1[C:7]([O:9][CH3:10])=[O:8].[H-].[Na+].Cl[C:17]([O:19][CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)=[O:18].C(O)C>C1COCC1.O>[CH:11]([C:5]1[C:6]([C:7]([O:9][CH3:10])=[O:8])=[C:2]([CH3:1])[N:3]([C:17]([O:19][CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[O:18])[C:4]=1[CH3:13])=[O:12]
Reactant: COC(=O)c1c(C)[nH]c(C)c1C=O
Reactant: O=C(Cl)OCc1ccccc1
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Solvent: CCO
Product: COC(=O)c1c(C=O)c(C)n(C(=O)OCc2ccccc2)c1C
Temperature: 10 °C
Reaction time: 4 h

Procedure:
Methyl 2,5-dimethyl-4-formyl-pyrrole-3-carboxylate (500 mg) in THF (5 ml) under nitrogen was added to a suspension of sodium hydride (120 mg of 60% oil dispersion) in dry THF (10 ml). When effervescence had ceased the suspension was cooled to 10° C., and benzyl chloroformate (0.437 ml) was added. After stirring at room temperature for 4 h, ethanol (0.5 ml) was added and then the reaction was poured into water. Extraction into ethyl acetate, washing the extracts with brine, drying and evaporation gave the crude product. Purification by chromatography (SiO2/30%-50% ethyl acetate in isohexane) afforded the subtitle compound (0.6 g).
Reaction SMILES: [F:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([C:12]2[CH2:17][CH2:16][CH:15]([N:18]3[CH2:23][CH2:22][N:21]([CH2:24][C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)[CH2:20][CH2:19]3)[CH2:14][CH:13]=2)=[CH:4][CH:3]=1>C(O)(=O)C.[Pt]=O>[F:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([C@H:12]2[CH2:13][CH2:14][C@H:15]([N:18]3[CH2:19][CH2:20][N:21]([CH2:24][C:25]4[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=4)[CH2:22][CH2:23]3)[CH2:16][CH2:17]2)=[CH:4][CH:3]=1
Reactant: Fc1ccc(C2=CCC(N3CCN(Cc4ccccc4)CC3)CC2)c2ccccc12
Agent: O=[Pt]
Solvent: CC(=O)O
Product: Fc1ccc([C@H]2CC[C@H](N3CCN(Cc4ccccc4)CC3)CC2)c2ccccc12

Procedure:
A mixture of platinum oxide (0.1 g) and 1-[4-(4-fluoro-1-naphthalenyl)-3-cyclohexen-1-yl]-4-(phenylmethyl)piperazine (1.1 g, 2.7 mmole) was hydrogenated for 13 hr in 20 ml acetic acid. The catalyst was removed and the solution concentrated in vacuo. The residue was suspended in water and the mixture basified with potassium carbonate. The mixture was extracted with ether, the extracts were dried over sodium sulfate and the solution concentrated in vacuo. The residue was purified by chromatography on silica gel eluting with 2-propanol-ethyl acetate-hexane (3:10:87). Fractions containing the less polar material were concentrated in vacuo to give the cis isomer (25%, mp: 130-132° C.). Calc'd for C27H31FN2.0.1H2O: C, 80.21%; H, 7.78%; N, 6.93%. Found: C, 80.12%; H, 7.80%; N, 6.89%.