Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([C:4]1[CH:9]=[CH:8][C:7]([N:10]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[CH:6][CH:5]=1)[CH:2]=[CH2:3].[Cl:23][SiH:24]([Cl:26])[Cl:25].C1(C)C=CC=CC=1>C(Cl)Cl>[C:11]1([N:10]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:7]2[CH:8]=[CH:9][C:4]([CH2:1][CH2:2][CH2:3][Si:24]([Cl:26])([Cl:25])[Cl:23])=[CH:5][CH:6]=2)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1
Reactant: Cl[SiH](Cl)Cl
Reactant: C=CCc1ccc(N(c2ccccc2)c2ccccc2)cc1
Solvent: Cc1ccccc1
Solvent: ClCCl
Product: Cl[Si](Cl)(Cl)CCCc1ccc(N(c2ccccc2)c2ccccc2)cc1
Temperature: 30 °C

Procedure:
To a solution of 17 (0.18 g, 0.65 mmol) in 25 mL dry CH2Cl2 at 25° C. under inert atmosphere was added H2PtCl6.xH2O (0.001 g), followed by trichlorosilane (0.88 g, 6.5 mmol). The reaction solution was warmed to 30° C. and monitored by NMR until the completion of reaction after 4 h. Removal of the solvent in vacuum yielded a oil. 20 mL dry toluene was added to the residue and filtered into a Schlenk flask by cannula. The filtrate was concentrated under vacuum to give 18 as a oil. Yield, 98%. 1H NMR (benzene): δ0.90 (t, J=8 Hz, 2H), 1.55 (m, 2H), 2.20 (t, J=8 Hz, 2H), 6.75-6.83 (m, 4H), 6.98-7.14 (m, 10H).
Reaction SMILES: [NH2:1][C:2]1[C:3]([NH:12][CH:13]2[CH2:15][CH2:14]2)=[C:4]([CH:9]=[CH:10][CH:11]=1)[C:5]([NH:7][CH3:8])=[O:6].[NH:16]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[C@H:17]([C:19](O)=[O:20])[CH3:18].CCN(C(C)C)C(C)C.C1CN([P+](ON2N=NC3C2=CC=CC=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F>CN(C=O)C.CCOC(C)=O>[CH:13]1([NH:12][C:3]2[C:4]([C:5](=[O:6])[NH:7][CH3:8])=[CH:9][CH:10]=[CH:11][C:2]=2[NH:1][C:19](=[O:20])[C@@H:17]([NH:16][C:22](=[O:23])[O:24][C:25]([CH3:27])([CH3:26])[CH3:28])[CH3:18])[CH2:15][CH2:14]1
Reactant: CNC(=O)c1cccc(N)c1NC1CC1
Reactant: C[C@H](NC(=O)OC(C)(C)C)C(=O)O
Agent: F[P-](F)(F)(F)(F)F
Agent: c1ccc2c(c1)nnn2O[P+](N1CCCC1)(N1CCCC1)N1CCCC1
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: CNC(=O)c1cccc(NC(=O)[C@H](C)NC(=O)OC(C)(C)C)c1NC1CC1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a solution of 3-amino-2-(cyclopropylamino)-N-methylbenzamide (1.31 g, 6.38 mmol) in DMF (3 mL) was added Boc-L-Ala-OH (1.21 g, 6.38 mmol), 1,1′-dimethyltriethylamine (2.22 mL, 12.8 mmol) and (1H-benzo[d][1,2,3]triazol-1-yloxy)tripyrrolidin-1-ylphosphonium hexafluorophosphate(V) (3.99 g, 7.66 mmol) the resulting mixture was stirred at rt for 2 h. The reaction mixture was diluted with EtOAc, washed with water, brine and dried over magnesium sulfate. After being concentrated under reduced pressure, the residue was purified by column chromatography on a silica gel column using EtOAc:DCM (1:1) as eluent to give (S)-tert-butyl 1-(2-(cyclopropylamino)-3-(methylcarbamoyl)phenylamino)-1-oxopropan-2-ylcarbamate: 1H NMR (400 MHz, CDCl3) δ 8.56 (br, 1H), 8.14 (d, J=8 Hz, 1H), 7.18 (d, J=8 Hz, 1H), 6.99 (dd, J=8, 8 Hz, 1H), 6.24 (br, 1H), 6.01 (br, 1H), 4.38 (br, 1H), 3.00 (d, J=4 Hz, 3H), 2.58 (br, 1H), 1.60 (s, 3H), 1.48 (s, 9H), 0.64-0.59 (m, 2H), 0.54-0.49 (m, 2H); LC-MS (ESI) m/z 377.2 [M+H]+.
Reaction SMILES: [C:1]([S:4][CH2:5][CH:6]([CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[C:7]([OH:9])=O)(=[O:3])[CH3:2].[CH2:17]([C:24]1[O:28][C:27]([C:29](=[N:35]O)[C:30]([O:32][CH2:33][CH3:34])=[O:31])=[CH:26][CH:25]=1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>C(Cl)(Cl)Cl>[CH2:33]([O:32][C:30](=[O:31])[CH:29]([C:27]1[O:28][C:24]([CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[CH:25][CH:26]=1)[NH:35][C:7](=[O:9])[CH:6]([CH2:5][S:4][C:1](=[O:3])[CH3:2])[CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[CH3:34]
Reactant: CCOC(=O)C(=NO)c1ccc(Cc2ccccc2)o1
Reactant: CC(=O)SCC(Cc1ccccc1)C(=O)O
Solvent: ClC(Cl)Cl
Product: CCOC(=O)C(NC(=O)C(CSC(C)=O)Cc1ccccc1)c1ccc(Cc2ccccc2)o1

Procedure:
The title compound was prepared from 2-(acetylthiomethyl)-3-phenylpropionic acid (US 4329495) and ethyl (5-benzyl)furan-2-yl-2-hydroxyiminoacetate (Description 42) by the procedure of Description 40. νmax (CHCl3) 3428, 1741 and 1683cm-1. m/z 479 M+). [Found (HRMS): m/z 479.1768. Calc. for C27H29NO5S; 479.1766].
Reaction SMILES: CN(C)C.[O:5]=O.[CH3:7][C:8]1[C:13]([CH3:14])=[CH:12][C:11]([CH3:15])=[CH:10][C:9]=1[OH:16]>C(Cl)(Cl)Cl>[CH3:15][C:11]1[C:12](=[O:5])[C:13]([CH3:14])=[C:8]([CH3:7])[C:9](=[O:16])[CH:10]=1
Reactant: Cc1cc(C)c(C)c(O)c1
Reactant: O=O
Agent: CN(C)C
Solvent: ClC(Cl)Cl
Product: CC1=CC(=O)C(C)=C(C)C1=O

Procedure:
0.4 g of cobalt di-(5-methylsalcylal)-3,3'-diimino-di-n-propylamine (0.0001 mole) was dissolved in chloroform. To this was added 0.2 ml of an aqueous solution of 30% trimethylamine (0.0001 mole), which had been dissolved in 20 ml of chloroform, followed by the introduction of oxygen thereinto, but very little oxygen was absorbed. Upon adding a solution of 1.36 g of 2,3,5-trimethylphenol (0.01 mole) in 200 ml of chloroform to the above solution, the absorption of oxygen started, and in 5 hours the theoretical amount of oxygen was absorbed (224 ml). After the reaction was completed, the chloroform was distilled off and the residue was subjected to steam-distillation. The distillate was extracted with ether and the ether was then distilled off to give 1.5 g of pseudocumoquinone, (0.01 mole), that is, the yield was quantitative.
Reaction SMILES: [CH3:1][N:2]([CH3:12])[C:3]([CH:5]1[CH:10]([CH3:11])[CH2:9][CH2:8][NH:7][CH2:6]1)=[O:4].C(N(CC)CC)C.Cl[C:21]1[N:26]=[C:25]([NH2:27])[C:24]([N+:28]([O-:30])=[O:29])=[CH:23][CH:22]=1>CS(C)=O.O>[NH2:27][C:25]1[N:26]=[C:21]([N:7]2[CH2:8][CH2:9][C@H:10]([CH3:11])[C@H:5]([C:3]([N:2]([CH3:12])[CH3:1])=[O:4])[CH2:6]2)[CH:22]=[CH:23][C:24]=1[N+:28]([O-:30])=[O:29]
Reactant: CC1CCNCC1C(=O)N(C)C
Reactant: Nc1nc(Cl)ccc1[N+](=O)[O-]
Solvent: O
Solvent: CCN(CC)CC
Solvent: CS(C)=O
Product: C[C@H]1CCN(c2ccc([N+](=O)[O-])c(N)n2)C[C@H]1C(=O)N(C)C
Temperature: 80 °C
Yield: 67.8 %

Procedure:
To a solution of N,N,4-trimethylpiperidine-3-carboxamide (0.16 g, 0.96 mmol) in dimethylsulfoxide (5 mL) were added triethylamine (0.2 mL, 0.96 mmol) and 6-chloro-3-nitropyridin-2-amine (0.168 g, 0.96 mmol). The reaction mixture was heated for 12 h at 80° C., then was cooled. The mixture was diluted with water and the aqueous layer was extracted with ethyl acetate (2×10 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified via silica gel chromatography to afford cis-1-(6-amino-5-nitropyridin-2-yl)-N,N,4-trimethylpiperidine-3-carboxamide (0.2 g, 68%).
Reaction SMILES: [N:1]1([C:7](Cl)=[O:8])[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.N1C=CC=CC=1.Cl.[CH2:17]([O:24][N:25]1[C:31](=[O:32])[N:30]2[CH2:33][C@H:26]1[CH2:27][CH2:28][C@H:29]2[C:34]([NH:36][NH2:37])=[O:35])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>CN(C1C=CN=CC=1)C.C(Cl)Cl>[CH2:17]([O:24][N:25]1[C:31](=[O:32])[N:30]2[CH2:33][C@H:26]1[CH2:27][CH2:28][C@H:29]2[C:34]([N:36]([C:7]([N:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1)=[O:8])[NH2:37])=[O:35])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1
Reactant: NNC(=O)[C@@H]1CC[C@@H]2CN1C(=O)N2OCc1ccccc1
Reactant: O=C(Cl)N1CCOCC1
Agent: CN(C)c1ccncc1
Agent: Cl
Solvent: c1ccncc1
Solvent: ClCCl
Product: NN(C(=O)[C@@H]1CC[C@@H]2CN1C(=O)N2OCc1ccccc1)C(=O)N1CCOCC1
Temperature: 0 °C
Reaction time: 0.33 h
Yield: 47.3 %

Procedure:
Morpholine-4-carbonyl chloride (297 mg, 1.99 mmol) was added dropwise over a period of 10 minutes to a solution of DMAP (24 mg, 0.199 mmol) and pyridine (0.16 mL, 1.99 mmol) in dry DCM (5 mL). The mixture was stirred at 0° C. for 20 minutes then, a solution of (2S,5R)-6-(benzyloxy)-7-oxo-1,6-diaza-bicyclo[3.2.1]octane-2-carbohydrazide hydrochloride (0.65 g, 1.99 mmol) in dry DCM (2.0 mL) was added over a period of 10 minutes. The mixture was stirred at 0° C. for 15 min and was then allowed to warm to rt and was stirred overnight. The reaction mixture was diluted with DCM (10 mL), and washed with 1N HCl (10 mL), and saturated sodium chloride (10 mL), then was dried over Na2SO4 and concentrated. The crude product was purified by silica gel column chromatography (0 to 1:100 MeOH/DCM, containing 1% TEA) to give N-((2S,5R)-6-(benzyloxy)-7-oxo-1,6-diaza-bicyclo[3.2.1]octane-2-carbonyl) morpholine-4-carbohydrazide (0.38 g, 47%) as a white solid. ESI-MS (EI+, m/z): 404.19 [M+H]+.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:30]=[CH:31][CH:32]=1)[O:5][CH2:6][CH2:7][CH2:8][O:9][C:10]1[CH:15]=[CH:14][C:13]([CH:16]2[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][CH:17]2[OH:29])=[CH:12][CH:11]=1.Cl[CH2:34][C:35]1[CH:36]=[CH:37][C:38]2[O:43][CH2:42][C:41](=[O:44])[N:40]([CH2:45][CH2:46][CH2:47][O:48][CH3:49])[C:39]=2[CH:50]=1>>[F:1][C:2]1[CH:3]=[C:4]([CH:30]=[CH:31][CH:32]=1)[O:5][CH2:6][CH2:7][CH2:8][O:9][C:10]1[CH:11]=[CH:12][C:13]([CH:16]2[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:27])([CH3:28])[CH3:26])=[O:23])[CH2:18][CH:17]2[O:29][CH2:34][C:35]2[CH:36]=[CH:37][C:38]3[O:43][CH2:42][C:41](=[O:44])[N:40]([CH2:45][CH2:46][CH2:47][O:48][CH3:49])[C:39]=3[CH:50]=2)=[CH:14][CH:15]=1
Reactant: CC(C)(C)OC(=O)N1CCC(c2ccc(OCCCOc3cccc(F)c3)cc2)C(O)C1
Reactant: COCCCN1C(=O)COc2ccc(CCl)cc21
Product: COCCCN1C(=O)COc2ccc(COC3CN(C(=O)OC(C)(C)C)CCC3c3ccc(OCCCOc4cccc(F)c4)cc3)cc21

Procedure:
Analogously to Method D, 1.1 g of tert-butyl 4-{4-[3-(3-fluorophenoxy)propoxy]phenyl}-3-hydroxypiperidine-1-carboxylate and 0.687 g of 6-chloromethyl-4(3-methoxypropyl)-4H-benzo[1,4]oxazin-3-one (Example 2a) are reacted. The title compound is obtained as an opaque oil. Rf=0.42 (1:1 EtOAc-heptane); Rt=5.97.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6]([Cl:8])[C:5]([CH2:9][NH:10][C:11]2[CH:16]=[CH:15][C:14]([CH2:17][CH3:18])=[CH:13][CH:12]=2)=[CH:4][N:3]=1.[N+](C1C=CC([O:28][C:29](=O)[NH:30][C@H:31]([CH3:41])[CH2:32][O:33][Si:34]([C:37]([CH3:40])([CH3:39])[CH3:38])([CH3:36])[CH3:35])=CC=1)([O-])=O.C(N(CC)CC)C>C1(C)C=CC=CC=1>[C:37]([Si:34]([CH3:36])([CH3:35])[O:33][CH2:32][C@H:31]([NH:30][C:29](=[O:28])[N:10]([CH2:9][C:5]1[C:6]([Cl:8])=[N:7][C:2]([Cl:1])=[N:3][CH:4]=1)[C:11]1[CH:16]=[CH:15][C:14]([CH2:17][CH3:18])=[CH:13][CH:12]=1)[CH3:41])([CH3:40])([CH3:39])[CH3:38]
Reactant: CCc1ccc(NCc2cnc(Cl)nc2Cl)cc1
Reactant: C[C@H](CO[Si](C)(C)C(C)(C)C)NC(=O)Oc1ccc([N+](=O)[O-])cc1
Solvent: Cc1ccccc1
Solvent: CCN(CC)CC
Product: CCc1ccc(N(Cc2cnc(Cl)nc2Cl)C(=O)N[C@H](C)CO[Si](C)(C)C(C)(C)C)cc1

Procedure:
A solution of (2,4-dichloro-pyrimidin-5-yl-methyl)-(4-ethyl-phenyl)amine (620 mg, 2.19 mmol) (from Example 38c supra), (R)-[2-(tert-butyl-dimethyl-silanyloxy)-1-methyl-ethyl]-carbamic acid 4-nitro-phenyl ester (778 mg, 2.19 mmol) (from Example 38b supra) and triethylamine (0.93 mL, 6.6 mmol) (Allied Signal) in toluene (20 mL) was heated at reflux for 48 hours. The reaction mixture was quenched at room temperature with 1 N aqueous hydrochloric acid then extracted with ethyl acetate. The combined organic layers were successively washed with 1 N aqueous sodium hydroxide solution and brine, then dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography (30% ethyl acetate in hexanes) to give (R)-3-[2-(tert-butyl-dimethyl-silanyloxy)-1-methyl-ethyl]-1-(2,4-dichloro-pyrimidin-5-yl-methyl)-1-(4-ethyl-phenyl)-urea. (Yield 383 mg, 36%).
Reaction SMILES: [C:1]([CH2:3][C:4]1([OH:17])[CH2:9][CH2:8][N:7]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:6][CH2:5]1)#[N:2].[H][H]>C(O)C.C(O)(=O)C.[Pt](=O)=O>[NH2:2][CH2:1][CH2:3][C:4]1([OH:17])[CH2:9][CH2:8][N:7]([C:10]([O:12][C:13]([CH3:15])([CH3:14])[CH3:16])=[O:11])[CH2:6][CH2:5]1
Reactant: CC(C)(C)OC(=O)N1CCC(O)(CC#N)CC1
Reactant: [H][H]
Agent: O=[Pt]=O
Solvent: CCO
Solvent: CC(=O)O
Product: CC(C)(C)OC(=O)N1CCC(O)(CCN)CC1

Procedure:
A solution of tert-butyl 4-(cyanomethyl)-4-hydroxypiperidine-1-carboxylate (example 89, step a) (1.4 g) in a mixture of ethanol (20 mL) and acetic acid (20 mL) was hydrogenated at 4 atmospheres pressure of hydrogen in the presence of platinum(IV) oxide (0.25 g) for 4 hours. The catalyst was filtered off and the solvents removed under reduced pressure. The residue was partitioned between dilute aqueous NaOH and ethyl acetate and the organic layer dried over sodium sulphate, filtered and the solvent evaporated under reduced pressure to afford the subtitled compound. Yield 1.1 g. Used directly.
Reaction SMILES: Cl[C:2]1[N:7]([CH3:8])[C:6](=[O:9])[N:5]([CH3:10])[C:4](=[O:11])[C:3]=1[CH:12]=[O:13].[CH2:14]([SH:16])[CH3:15]>>[CH2:14]([S:16][C:2]1[N:7]([CH3:8])[C:6](=[O:9])[N:5]([CH3:10])[C:4](=[O:11])[C:3]=1[CH:12]=[O:13])[CH3:15]
Reactant: CCS
Reactant: Cn1c(Cl)c(C=O)c(=O)n(C)c1=O
Product: CCSc1c(C=O)c(=O)n(C)c(=O)n1C

Procedure:
The process described in Method D was followed. 6-Chloro-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carbaldehyde (0.303 g, 1.50 mmol) and ethanethiol were used to obtain the title compound. The crude product was purified by column chromatography with a mixture of n-hexane:ethyl acetate (1:1) as the eluent.
Reaction SMILES: [CH3:1][O:2][C:3]1[C:10]([O:11][CH3:12])=[CH:9][C:6]([CH:7]=[O:8])=[C:5](Br)[CH:4]=1.C(=O)([O-])[O-].[Na+].[Na+].[CH3:20][O:21][C:22]1[CH:23]=[C:24](B(O)O)[CH:25]=[CH:26][CH:27]=1>C1(C)C=CC=CC=1.C(O)C.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>[CH3:20][O:21][C:22]1[CH:27]=[C:26]([C:5]2[CH:4]=[C:3]([O:2][CH3:1])[C:10]([O:11][CH3:12])=[CH:9][C:6]=2[CH:7]=[O:8])[CH:25]=[CH:24][CH:23]=1
Reactant: COc1cc(Br)c(C=O)cc1OC
Reactant: COc1cccc(B(O)O)c1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCO
Solvent: Cc1ccccc1
Product: COc1cccc(-c2cc(OC)c(OC)cc2C=O)c1
Reaction time: 1 h
Yield: 97.2 %

Procedure:
Tetrakis(triphenylphosphine)palladium(0) (0.36 g) was added to a solution of 4,5-dimethoxy-2-bromobenzaldehyde (2.5 g) in toluene (20 ml) and ethanol (20 ml), followed by addition of 2M aqueous sodium carbonate (20 ml). To this mixture was added 3-methoxyphenylboronic acid (1.7 g), and the mixture was heated to reflux. After 1 hour, the reaction was partitioned between water (150 ml) and ethyl acetate (300 ml). The organic layer was washed with saturated aqueous sodium bicarbonate (150 ml) and brine (150 ml), dried over magnesium sulfate and concentrated. Chromatography (silica, 20-30-40% ethyl acetate/hexanes) afforded 2.7 g (98%) of 2-(3-methoxyphenyl)-4,5-dimethoxybenzaldehyde as a yellow oil which solidified upon standing.
Reaction SMILES: C([O:3][C:4]([C:6]1[CH:11]=[CH:10][C:9]([CH2:12][NH:13][C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])=[CH:8][N:7]=1)=[O:5])C.[OH-].[Li+:22]>O.C1COCC1>[C:17]([O:16][C:14]([NH:13][CH2:12][C:9]1[CH:10]=[CH:11][C:6]([C:4]([O-:5])=[O:3])=[N:7][CH:8]=1)=[O:15])([CH3:20])([CH3:18])[CH3:19].[Li+:22]
Reactant: CCOC(=O)c1ccc(CNC(=O)OC(C)(C)C)cn1
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Product: CC(C)(C)OC(=O)NCc1ccc(C(=O)[O-])nc1
Temperature: 25 °C
Reaction time: 4 h
Yield: 118.1 %

Procedure:
Dissolve 5-aminomethyl-2-chloro-pyridine (2 g, 14 mmol) and di-tert-butyl-dicarbonate (3.37 g, 15.4 mmol) in DCM (30 mL) and stir at room temperature for 2 h. Concentrate the reaction mixture and purify by chromatography on silica gel eluting with hexane/EtOAc (10:1 and 5:1) to give 5-(tert-butoxycarbonylamino-methyl)-2-chloro-pyridine as a yellow solid (3.6 g, 100%). MS (ES+) m/z: 243 (M+H)+. Dissolve 5-tert-butoxycarbonylamino-methyl)-2-chloro-pyridine (1 g, 4.12 mmol) in a mixture of ethanol (15 mL) and DMF (5 mL), and add potassium carbonate (427 mg, 3.09 mmol), palladium(II) acetate (92 mg, 0.4 mmol) and diphenylphosphinoferrocene (240 mg, 0.44 mmol). Pressurize the mixture 25 to 15 psi with carbon monoxide gas and heat the reaction mixture to 90° C. for 16 h. Filter the reaction mixture, concentrate the filtrate, and partition the residue between water and hexane/EtOAc (1:1). Dry the organic layer over Na2SO4, filter, and concentrate in vacuo. Purify the residue by chromatography on silica gel eluting with hexane/EtOAc (3:2) to give 5-(tert-butoxycarbonylamino-methyl)-pyridine-2-carboxylic acid ethyl ester as a brown oil (920 mg, 80%). MS (ES+) m/z: 281 (M+H)+. Dissolve 5-(tert-butoxycarbonylamino-methyl)pyridine-2-carboxylic acid ethyl ester (920 mg, 3.28 mmol) in a mixture of water/THF (1:2, 15 mL) and add lithium hydroxide (87 mg, 3.61 mmol). Stir the mixture at ambient temperature for 4 h and concentrate to a solid. Dry the material by azeotrope distillation with toluene to give the desired intermediate as a brown solid (1 g, 100%). MS (ES+) m/z: 253 (M+H)+.
Reaction SMILES: [CH3:1][C:2]1([C:7]2[S:11][C:10]([CH2:12][N:13]3[N:17]=[C:16]([NH2:18])[CH:15]=[N:14]3)=[CH:9][CH:8]=2)[O:6]CCO1.[F:19][C:20]1[CH:25]=[CH:24][C:23]([C:26]2[O:30][CH:29]=[N:28][C:27]=2[C:31](O)=[O:32])=[CH:22][CH:21]=1>>[C:2]([C:7]1[S:11][C:10]([CH2:12][N:13]2[N:17]=[C:16]([NH:18][C:31]([C:27]3[N:28]=[CH:29][O:30][C:26]=3[C:23]3[CH:24]=[CH:25][C:20]([F:19])=[CH:21][CH:22]=3)=[O:32])[CH:15]=[N:14]2)=[CH:9][CH:8]=1)(=[O:6])[CH3:1]
Reactant: O=C(O)c1ncoc1-c1ccc(F)cc1
Reactant: CC1(c2ccc(Cn3ncc(N)n3)s2)OCCO1
Product: CC(=O)c1ccc(Cn2ncc(NC(=O)c3ncoc3-c3ccc(F)cc3)n2)s1

Procedure:
Following general procedure A followed by B, starting from 2-[5-(2-methyl-[1,3]dioxolan-2-yl)-thiophen-2-ylmethyl]-2H-[1,2,3]triazol-4-ylamine and 5-(4-fluoro-phenyl)-oxazole-4-carboxylic acid.
Reaction SMILES: [CH3:1][C:2]([CH3:33])([CH3:32])[C:3](=[O:31])[CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]([C:17]2[CH:18]=[C:19]([CH3:29])[C:20]3[O:24][C:23]([C:25]([OH:27])=[O:26])=[CH:22][C:21]=3[CH:28]=2)([CH2:15][CH3:16])[CH2:13][CH3:14])=[CH:8][C:7]=1[CH3:30].[BH4-].[Na+]>C1COCC1>[CH2:13]([C:12]([C:17]1[CH:18]=[C:19]([CH3:29])[C:20]2[O:24][C:23]([C:25]([OH:27])=[O:26])=[CH:22][C:21]=2[CH:28]=1)([C:9]1[CH:10]=[CH:11][C:6]([O:5][CH2:4][CH:3]([OH:31])[C:2]([CH3:32])([CH3:33])[CH3:1])=[C:7]([CH3:30])[CH:8]=1)[CH2:15][CH3:16])[CH3:14]
Reactant: CCC(CC)(c1ccc(OCC(=O)C(C)(C)C)c(C)c1)c1cc(C)c2oc(C(=O)O)cc2c1
Agent: [BH4-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CCC(CC)(c1ccc(OCC(O)C(C)(C)C)c(C)c1)c1cc(C)c2oc(C(=O)O)cc2c1
Reaction time: 1 h
Yield: 67.7 %

Procedure:
A solution of 5-{1-[4-(3,3-dimethyl-2-oxo-butoxy)-3-methyl-phenyl]-1-ethyl-propyl}-7-methyl-benzofuran-2-carboxylic acid (250 mg, 0.555 mmol) in THF (10 mL) at RT is treated with NaBH4 (42 mg, 1.11 mmol). The resulting mixture is stirred for 60 min and is quenched with HCl (1.0 N, 5.0 mL) and extracted with EtOAc (2×30 mL). The organic layer is dried over Na2SO4, concentrated to afford the title compound (170 mg, 68%).
Reaction SMILES: [CH2:1]=[CH2:2].[CH2:3]=[CH:4][CH2:5][CH3:6]>>[CH2:4]1[CH:3]2[CH:5]3[CH:4]=[CH:3][CH:2]([CH:1]2[CH:6]=[CH:5]1)[CH2:6]3
Reactant: C=CCC
Reactant: C=C
Product: C1=CC2C3C=CC(C3)C2C1

Procedure:
When the copolymerization reaction was performed under the conditions described above, a copolymer of ethylene, 1-butene and dicyclopentadiene was obtained as a uniform solution. A small amount of methanol was added to the polymer solution withdrawn from the bottom of the polymerization vessel to stop the polymerization reaction. The polymer was separated from the solvent by steam stripping, and dried under reduced pressure at 80° C. for one day.
Reaction SMILES: [F:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([N+:12]([O-:14])=[O:13])[CH:10]=2)[C:5](=O)[NH:4][CH:3]=1.P(Cl)(Cl)([Cl:18])=O>>[Cl:18][C:5]1[C:6]2[C:11](=[CH:10][C:9]([N+:12]([O-:14])=[O:13])=[CH:8][CH:7]=2)[C:2]([F:1])=[CH:3][N:4]=1
Reactant: O=P(Cl)(Cl)Cl
Reactant: O=c1[nH]cc(F)c2cc([N+](=O)[O-])ccc12
Product: O=[N+]([O-])c1ccc2c(Cl)ncc(F)c2c1
Temperature: 115 °C
Yield: 104.2 %

Procedure:
To Intermediate 3E (8.8 g, 36.0 mmol) was added phosphoryl trichloride (59.3 mL, 648 mmol). The suspension was heated at 115° C. for 1.0 h. Solvent was removed under high vacuum. The residue was diluted with EtOAc, washed with sat. sodium bicarbonate, brine and dried over sodium sulfate. After evaporation of solvent, the crude product was dissolved in a small amount of chloroform and charged to a 120 g silica gel cartridge which was eluted with 2% EtOAc in hexanes for 6 min, then a 15 min gradient from 2% to 25% EtOAc in hexanes. The desired fractions were combined and concentrated to give Intermediate 3F (8.5 g, 37.5 mmol, 104% yield) as a slightly yellow solid. 1H NMR (400 MHz, chloroform-d) δ ppm 9.01 (s, 1H) 8.46-8.56 (m, 2H) 8.34 (s, 1H); 19F NMR (376 MHz, chloroform-d) δ ppm −136.54 (s, 1F); MS (ESI) m/z: (M+H)+ 227.1.
Reaction SMILES: C([O:3][C:4](=O)[CH2:5][C:6]([CH:8]1[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]1)=O)C.[NH2:15][NH2:16]>C(O)C.C(O)(=O)C>[CH:8]1([C:6]2[CH2:5][C:4](=[O:3])[NH:16][N:15]=2)[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]1
Reactant: CCOC(=O)CC(=O)C1CCCCC1
Reactant: NN
Solvent: CC(=O)O
Solvent: CCO
Product: O=C1CC(C2CCCCC2)=NN1
Reaction time: 18 h

Procedure:
3-Cyclohexyl-3-oxo-propionic acid ethyl ester (0.5 g, 2.52 mmol) was stirred in ethanol and acetic acid (10:1, 2:0.2 mL), and treated with hydrazine (0.095 mL, 3.03 mmol). After 18 hrs, the resulting solid was filtered off and washed with a minimum amount of ethanol to yield 3-cyclohexyl-1H-pyrazol-5(4H)-one. Then, the 3-cyclohexyl-1H-pyrazol-5(4H)-one (0.2 g, 1.23 mmol) and 4-chloroquinoline N-oxide (1.23 mmol) were stirred in acetic anhydride (20 mL) at ambient temperature for 60-90 minutes. The reaction mixture was concentrated and the resulting solid filtered off and washed with a minimum amount of ether. (Z)-4-(4-chloroquinolin-2(1H)-ylidene)-3-cyclohexyl-1H-pyrazol-5(4H)-one (0.05 g, 0.13 mmol) was dissolved in ethanol (1.5 mL) and 4-acetamidothiophenol (0.023 g, 0.13 mmol) was added. The reaction mixture was heated to 180° C. using a microwave reactor for 5-10 minutes. The solid was filtered and washed with ethanol to yield Example 48. 1H NMR (400 MHz, DMSO-d6) δ ppm 0.88-1.00 (m, 2H) 1.26-1.38 (m, 2H) 1.58 (d, J=10.61 Hz, 6H) 2.10 (s, 3H) 2.33 (t, J=9.47 Hz, 1H) 6.87 (s, 1H) 7.62-7.72 (m, 3H) 7.89 (t, J=7.83 Hz, 4H) 8.17 (d, J=8.34 Hz, 1H) 10.37 (s, 1H); ESI-MS: m/z calc'd for C26H26N4O2S 458.58. found 459.1 (M+H)+.
Reaction SMILES: C[C@H]1CN(C)[C@H](C)CN1C1C=CC(N)=CC=1.[F:17][C:18]1[CH:23]=[C:22]([N+:24]([O-])=O)[CH:21]=[CH:20][C:19]=1[N:27]1[CH2:32][C@@H:31]([CH3:33])[N:30]([CH3:34])[C@@H:29]([CH3:35])[CH2:28]1>[Pd]>[F:17][C:18]1[CH:23]=[C:22]([NH2:24])[CH:21]=[CH:20][C:19]=1[N:27]1[CH2:32][C@H:31]([CH3:33])[N:30]([CH3:34])[C@H:29]([CH3:35])[CH2:28]1
Reactant: C[C@@H]1CN(c2ccc([N+](=O)[O-])cc2F)C[C@H](C)N1C
Agent: [Pd]
Agent: C[C@@H]1CN(c2ccc(N)cc2)[C@@H](C)CN1C
Product: C[C@@H]1CN(c2ccc(N)cc2F)C[C@H](C)N1C
Yield: 84.3 %

Procedure:
Using the method described above for the synthesis of racemic-4-(trans-2,4,5-Trimethyl-piperazin-1-yl)-phenylamine, treatment of cis-4-(2-fluoro-4-nitrophenyl)-1,2,6-trimethylpiperazine (1.39 g, 5.20 mmol) with H2 and 10% Pd/C (120 mg) provided crude 3-fluoro-4-(cis-3,4,5-trimethyl-piperazin-1-yl)-phenylamine (1.04 g, 84% recovery, 96% purity as determined by LC/MS analysis @ UV 254 nm detection,). The crude product is used in the next step without further purification. LCMS-ESI (m/z): calcd for C13H20FN3, 237; [M+H]+ found, 238.
Reaction SMILES: [CH:1]([C:3]1[NH:7][C:6]([CH3:8])=[C:5]([C:9]2[CH:17]=[CH:16][C:12]([C:13]([OH:15])=O)=[CH:11][CH:10]=2)[C:4]=1[CH3:18])=[O:2].[NH:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1>>[CH3:18][C:4]1[C:5]([C:9]2[CH:10]=[CH:11][C:12]([C:13]([N:19]3[CH2:24][CH2:23][O:22][CH2:21][CH2:20]3)=[O:15])=[CH:16][CH:17]=2)=[C:6]([CH3:8])[NH:7][C:3]=1[CH:1]=[O:2]
Reactant: C1COCCN1
Reactant: Cc1[nH]c(C=O)c(C)c1-c1ccc(C(=O)O)cc1
Product: Cc1[nH]c(C=O)c(C)c1-c1ccc(C(=O)N2CCOCC2)cc1

Procedure:
4-(5-Formyl-2,4-dimethyl-1H-pyrrol-3-yl)-benzoic acid was reacted with morpholine using General Amidation Procedure 1 to give 3,5-dimethyl-4-[4-(morpholine-4-carbonyl)-phenyl]-1H-pyrrole-2-carbaldehyde. MS m/z 313 [M+1].