Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[C:7]([Cl:8])=[C:6]([O:9][CH3:10])[CH:5]=[CH:4][C:3]=1[SH:11].F[C:13]1[CH:18]=[CH:17][C:16]([N+:19]([O-:21])=[O:20])=[CH:15][CH:14]=1.C(=O)([O-])[O-].[K+].[K+].CN(C=O)C>O>[Cl:8][C:7]1[C:2]([Cl:1])=[C:3]([S:11][C:13]2[CH:18]=[CH:17][C:16]([N+:19]([O-:21])=[O:20])=[CH:15][CH:14]=2)[CH:4]=[CH:5][C:6]=1[O:9][CH3:10]
Reactant: O=[N+]([O-])c1ccc(F)cc1
Reactant: COc1ccc(S)c(Cl)c1Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: COc1ccc(Sc2ccc([N+](=O)[O-])cc2)c(Cl)c1Cl

Procedure:
A mixture of 2,3-dichloro-4-methoxybenzenethiol (6.0 g., 0.024 mole), p-fluoronitrobenzene (3.04 ml., 0.029 mole) and anhydrous potassium carbonate (5.15 g., 0.038 mole) in 60 ml. of DMF was stirred at room temperature for 2 hours and then poured into water. The resulting solid product was filtered and washed well with ethanol to give 9.1 g. (96%), m.p. 236°-237°.
Reaction SMILES: [N:1]([CH2:4][CH2:5][O:6][CH2:7][CH2:8][O:9][CH2:10][C:11]#[CH:12])=[N+]=[N-].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O>C1COCC1>[CH2:10]([O:9][CH2:8][CH2:7][O:6][CH2:5][CH2:4][NH2:1])[C:11]#[CH:12]
Reactant: C#CCOCCOCCN=[N+]=[N-]
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Solvent: O
Product: C#CCOCCOCCN
Temperature: 25 °C
Reaction time: 10 h
Yield: 79.8 %

Procedure:
3-(2-(2-azidoethoxy)ethoxy)prop-1-yne (s-4) (2 g, 11.82 mmol, 1.0 equiv) was dissolved in THF (30.5 mL). Triphenylphosphine (3.72 g, 14.20 mmol, 1.2 equiv.) and water (0.21 mL, 11.83 mol, 1.0 equiv.) were added to the solution and the reaction was allowed to stir at room temperature for 10 hours. The reaction was concentrated under reduced pressure and chromatographed (5% CH3OH in CHCl3, then 5% CH3OH in CHCl3+5% Et3N) to yield 2-(2-(prop-2-ynyloxy)ethoxy)ethanamine (s-5) as a pale green oil (1.35 g, 80%). IR (thin film) 3250 (m), 2863 (m), 2112 (w), 1589 (w), 1443 (w), 1349 (m), 1291 (w), 1093 (s), 1037 (m), 918 (w), 840 (w), 673 (m); 1H NMR (500 MHz, CDCl3) δ 4.21 (d, J=2.3 Hz, 2H), 3.73-3.68 (m, 2H), 3.68-3.62 (m, 2H), 3.51 (t, J=5.2 Hz, 2H), 2.87 (t, J=5.2 Hz, 2H), 2.43 (dd, J=2.4 Hz, 1H). 13C NMR (125 MHz, CDCl3) δ 79.7, 74.7, 73.7, 70.3, 69.2, 58.6, 41.9. HRMS (ES+) calc'd for C7H13NO2 (M+H) m/z 144.0980 Found 144.1019.
Reaction SMILES: [CH2:1]([O:3][N:4]=[C:5]([C:11](=O)[CH2:12]Cl)[C:6]([O:8][CH2:9][CH3:10])=[O:7])[CH3:2].[NH2:15][C:16]([NH2:18])=[S:17].C([O-])(=O)C.[Na+].C(=O)(O)[O-].[Na+]>O.CO>[CH2:1]([O:3][N:4]=[C:5]([C:11]1[N:15]=[C:16]([NH2:18])[S:17][CH:12]=1)[C:6]([O:8][CH2:9][CH3:10])=[O:7])[CH3:2]
Reactant: CCON=C(C(=O)CCl)C(=O)OCC
Reactant: NC(N)=S
Agent: CC(=O)[O-]
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CO
Solvent: O
Product: CCON=C(C(=O)OCC)c1csc(N)n1
Temperature: 48 °C
Reaction time: 0.67 h
Yield: 34.8 %

Procedure:
A mixture of ethyl 2-ethoxyimino-3-oxo-4-chlorobutyrate (syn isomer) (38.7 g.), thiourea (13.2 g.), sodium acetate (14.3 g.), methanol (95 ml.) and water (95 ml.) was stirred at 48° C. for 40 minutes. After the resultant solution was adjusted to pH 6.5 with an aqueous solution of sodium bicarbonate, the appeared precipitates were collected by filtration and washed with diisopropyl ether to give ethyl 2-ethoxyimino-2-(2-aminothiazol-4-yl)acetate (syn isomer) (14.7 g.), mp. 130° to 131° C.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:17])[CH2:4][C:5]1[C:9]2[C:10]([CH:15]=[CH2:16])=[CH:11][C:12]([OH:14])=[CH:13][C:8]=2[S:7][CH:6]=1.[CH3:18][C:19]1[C:24]([CH2:25]O)=[CH:23][CH:22]=[C:21]([CH3:27])[N:20]=1.C1CCN(C(N=NC(N2CCCCC2)=O)=O)CC1.C(P(CCCC)CCCC)CCC>C1COCC1>[CH3:1][O:2][C:3](=[O:17])[CH2:4][C:5]1[C:9]2[C:10]([CH:15]=[CH2:16])=[CH:11][C:12]([O:14][CH2:25][C:24]3[C:19]([CH3:18])=[N:20][C:21]([CH3:27])=[CH:22][CH:23]=3)=[CH:13][C:8]=2[S:7][CH:6]=1
Reactant: Cc1ccc(CO)c(C)n1
Reactant: C=Cc1cc(O)cc2scc(CC(=O)OC)c12
Agent: CCCCP(CCCC)CCCC
Agent: O=C(N=NC(=O)N1CCCCC1)N1CCCCC1
Solvent: C1CCOC1
Product: C=Cc1cc(OCc2ccc(C)nc2C)cc2scc(CC(=O)OC)c12
Yield: 88.4 %

Procedure:
To a mixture of methyl(6-hydroxy-4-vinyl-1-benzothiophen-3-yl)acetate (351 mg) and THF (dry) (3 mL) were added (2,6-dimethylpyridin-3-yl)methanol (233 mg), ADDP (535 mg) and tri-n-butylphosphine (0.523 mL) at room temperature. The precipitate was removed by filtration, and the filtrate was concentrated in vacuo. The residue was purified by silica gel column chromatography (EtOAc/hexane) to give the title compound (459 mg).
Reaction SMILES: [Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([N:21]([CH2:28][CH2:29][CH:30]3[CH2:34][CH2:33][CH2:32][N:31]3[CH3:35])C(=O)C(F)(F)F)=[C:7]([C:13]3[CH:18]=[C:17]([CH3:19])[CH:16]=[C:15]([CH3:20])[CH:14]=3)[C:8](=[O:12])[NH:9]2)=[CH:4][C:3]=1[N+:36]([O-:38])=[O:37].C(=O)([O-])[O-].[K+].[K+]>CO.O>[Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([NH:21][CH2:28][CH2:29][CH:30]3[CH2:34][CH2:33][CH2:32][N:31]3[CH3:35])=[C:7]([C:13]3[CH:14]=[C:15]([CH3:20])[CH:16]=[C:17]([CH3:19])[CH:18]=3)[C:8](=[O:12])[NH:9]2)=[CH:4][C:3]=1[N+:36]([O-:38])=[O:37]
Reactant: Cc1cc(C)cc(-c2c(N(CCC3CCCN3C)C(=O)C(F)(F)F)c3cc([N+](=O)[O-])c(Cl)cc3[nH]c2=O)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Solvent: O
Product: Cc1cc(C)cc(-c2c(NCCC3CCCN3C)c3cc([N+](=O)[O-])c(Cl)cc3[nH]c2=O)c1
Temperature: 60 °C
Reaction time: 4 h

Procedure:
To a solution of N-[7-chloro-3-(3,5-dimethylphenyl)-6-nitro-2-oxo-1,2-dihydroquinolin-4-yl]-2,2,2-trifluoro-N-[2-(1-methylpyrrolidin-2-yl)-ethyl]acetamide (50 mg in a mixture of 1.0 mL methanol and 0.10 mL water) was added 25 mg potassium carbonate and the mixture heated to 60° C. After 4 hours, the mixture was cooled to room temperature and the solvent removed in vacuo. The residue was dissolved in ethyl acetate and washed sequentially with water and brine then dried over sodium sulfate. Purification of the concentrate by flash chromatography on silica gel (chloroform:methanol:ammonium hydroxide, 90:10:1) gave the title compound (31 mg). MASS: 455 (M+H)
Reaction SMILES: F[B-](F)(F)F.[C:6]([PH+](C(C)(C)C)C(C)(C)C)(C)(C)[CH3:7].C[Si](C#C)(C)C.Br[C:26]1[CH:27]=[CH:28][C:29]2[N:30]([C:32]([CH2:35][O:36][C:37]3[C:46]4[C:41](=[CH:42][C:43]([O:47][CH3:48])=[CH:44][CH:45]=4)[N:40]=[CH:39][CH:38]=3)=[N:33][N:34]=2)[CH:31]=1>O1CCOCC1.C(N(CC)CC)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].[Cu]I>[C:6]([C:26]1[CH:27]=[CH:28][C:29]2[N:30]([C:32]([CH2:35][O:36][C:37]3[C:46]4[C:41](=[CH:42][C:43]([O:47][CH3:48])=[CH:44][CH:45]=4)[N:40]=[CH:39][CH:38]=3)=[N:33][N:34]=2)[CH:31]=1)#[CH:7]
Reactant: CC(C)(C)[PH+](C(C)(C)C)C(C)(C)C
Reactant: COc1ccc2c(OCc3nnc4ccc(Br)cn34)ccnc2c1
Agent: [Cu]I
Agent: [Pd]
Agent: C#C[Si](C)(C)C
Solvent: CCN(CC)CC
Solvent: C1COCCO1
Product: C#Cc1ccc2nnc(COc3ccnc4cc(OC)ccc34)n2c1
Temperature: 80 °C
Reaction time: 0.5 h

Procedure:
Tri-t-butylphosphonium tetrafluoroborate (0.0377 g, 0.130 mmol), tris(dibenzylideneacetone)dipalladium (0.0594 g, 0.0649 mmol), trimethylsilyl acetylene (1.82 ml, 13.0 mmol), 4-((6-bromo-[1,2,4]triazolo[4,3-a]pyridin-3-yl)methoxy)-7-methoxyquinoline (0.500 g, 1.30 mmol) were taken up in dioxane (10 mL) and triethylamine (3 mL). Added CuI. Sealed in a tube and heated at 80° C. for 3 h. Concentrated. Took up in MeOH and added solid potassium carbonate (large excess). Allowed to stir for 30 min. Filtered through a plug of Celite and concentrated. Took up in 10% MeOH in DCM and filtered through a plug of silica gel to afford 4-((6-ethynyl-[1,2,4]triazolo[4,3-a]pyridin-3-yl)methoxy)-7-methoxyquinoline. MS m/z=331.0 [M+1]+. Calc'd for C19H14N4O2: 330.3.
Reaction SMILES: [C:1]([C:5]1[N:6]=[C:7]([N:22]2[CH2:27][CH2:26]O[CH2:24][CH2:23]2)[C:8]2[N:13]=[N:12][N:11]([CH2:14][C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=3[Cl:21])[C:9]=2[N:10]=1)([CH3:4])([CH3:3])[CH3:2].C(C1N=C(Cl)C2N=[N:39][N:38]([CH2:41][C:42]3[CH:47]=CC=CC=3Cl)[C:36]=2N=1)(C)(C)C.CN1C=CC(C2CCCN2)=N1>>[C:1]([C:5]1[N:6]=[C:7]([N:22]2[CH2:27][CH2:26][CH2:24][CH:23]2[C:47]2[CH:42]=[CH:41][N:38]([CH3:36])[N:39]=2)[C:8]2[N:13]=[N:12][N:11]([CH2:14][C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=3[Cl:21])[C:9]=2[N:10]=1)([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)c1nc(N2CCOCC2)c2nnn(Cc3ccccc3Cl)c2n1
Reactant: CC(C)(C)c1nc(Cl)c2nnn(Cc3ccccc3Cl)c2n1
Agent: Cn1ccc(C2CCCN2)n1
Product: Cn1ccc(C2CCCN2c2nc(C(C)(C)C)nc3c2nnn3Cc2ccccc2Cl)n1

Procedure:
In analogy to the procedure described for the synthesis of 5-tert-butyl-3-(2-chlorobenzyl)-7-morpholin-4-yl-3H-[1,2,3]triazolo[4,5-d]pyrimidine (example 1, step c), the title compound was prepared from 5-tert-butyl-7-chloro-3-(2-chlorobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine and 1-methyl-3-(pyrrolidin-2-yl)-1H-pyrazole. MS(m/e): 451.4
Reaction SMILES: [CH:1]([N:14]1[CH2:17][CH:16]([CH2:18][O:19][C:20]2[C:28]([CH:29]3[CH2:31][CH2:30]3)=[CH:27][C:23]([C:24](O)=[O:25])=[C:22]([F:32])[CH:21]=2)[CH2:15]1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:33]1([S:36]([NH2:39])(=[O:38])=[O:37])[CH2:35][CH2:34]1>>[CH:1]([N:14]1[CH2:15][CH:16]([CH2:18][O:19][C:20]2[C:28]([CH:29]3[CH2:31][CH2:30]3)=[CH:27][C:23]([C:24]([NH:39][S:36]([CH:33]3[CH2:35][CH2:34]3)(=[O:38])=[O:37])=[O:25])=[C:22]([F:32])[CH:21]=2)[CH2:17]1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=C(O)c1cc(C2CC2)c(OCC2CN(C(c3ccccc3)c3ccccc3)C2)cc1F
Reactant: NS(=O)(=O)C1CC1
Product: O=C(NS(=O)(=O)C1CC1)c1cc(C2CC2)c(OCC2CN(C(c3ccccc3)c3ccccc3)C2)cc1F

Procedure:
The compound was prepared in a similar manner to Example 408 from 4-((1-benzhydrylazetidin-3-yl)methoxy)-5-cyclopropyl-2-fluorobenzoic acid and cyclopropanesulfonamide. LCMS (Method D): RT=4.69 min, m/z: 535.2 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ 11.75 (s, 1H), 7.48-7.36 (m, 4H), 7.28 (t, J=7.4 Hz, 4H), 7.23-7.09 (m, 3H), 6.96 (d, J=12.8 Hz, 1H), 4.50 (s, 1H), 4.22 (d, J=6.1 Hz, 2H), 3.12-2.96 (m, 3H), 2.94-2.80 (m, 1H), 2.12-1.99 (m, 1H), 1.18-0.97 (m, 4H), 0.95-0.82 (m, 2H), 0.73-0.60 (m, 2H).
Reaction SMILES: [C:1]([Si:5]([CH3:35])([CH3:34])[O:6][CH2:7][CH2:8][N:9]([CH2:21][C:22]1[CH:27]=[CH:26][C:25]([CH:28]=[CH:29][C:30]([O:32]C)=[O:31])=[CH:24][CH:23]=1)[CH2:10][CH2:11][C:12]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[NH:14][CH:13]=1)([CH3:4])([CH3:3])[CH3:2].O[Li].O>C1COCC1.O>[C:1]([Si:5]([CH3:35])([CH3:34])[O:6][CH2:7][CH2:8][N:9]([CH2:21][C:22]1[CH:27]=[CH:26][C:25]([CH:28]=[CH:29][C:30]([OH:32])=[O:31])=[CH:24][CH:23]=1)[CH2:10][CH2:11][C:12]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[NH:14][CH:13]=1)([CH3:3])([CH3:4])[CH3:2]
Reactant: COC(=O)C=Cc1ccc(CN(CCO[Si](C)(C)C(C)(C)C)CCc2c[nH]c3ccccc23)cc1
Agent: [Li]O
Solvent: C1CCOC1
Solvent: O
Product: CC(C)(C)[Si](C)(C)OCCN(CCc1c[nH]c2ccccc12)Cc1ccc(C=CC(=O)O)cc1
Yield: 78.8 %

Procedure:
To a stirred solution of compound 3 (3.18 g, 6.45 mmol) in THF (40 mL) was added a solution of LiOH.H2O (677 mg, 16.14 mmol) in water (20 mL) at room temperature. After 24 h the reaction mixture was concentrated, diluted with water and acidified with 1N HCl until a pH 5-6. A precipitate was formed which was separated by filtration, rinsed with water and dried to afford the title compound 4 (2.43 g, 5.08 mmol, 79% yield) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ(ppm): 12.34 (bs, 1H), 10.75 (s, 1H), 7.63 (d, J=8.2 Hz, 2H), 7.59 (d, J=15.8 Hz, 1H), 7.44-7.35 (m, 3H), 7.32 (d, J=8.0 Hz, 1H), 7.11 (d, J=2.3 Hz, 1H), 7.05 (td, J=7.5, 1.0 Hz, 1H), 6.92 (td, J=7.4, 0.9 Hz, 1H), 6.51 (d, J=15.8 Hz, 1H), 3.79 (s, 2H), 3.69 (t, J=6.4 Hz, 2H), 2.93-2.74 (m, 4H), 2.69 (t, J=6.2 Hz, 2H), 0.88 (s, 9H), 0.05 (s, 6H).
Reaction SMILES: [C:1]([C:4]1[C:9]([NH:10][C:11](=[O:18])[CH2:12][C:13]([O:15][CH2:16][CH3:17])=[O:14])=[CH:8][C:7]([C:19]([F:22])([F:21])[F:20])=[CH:6][N:5]=1)(=O)[CH3:2].[H-].[Na+]>C(O)C>[OH:18][C:11]1[C:12]([C:13]([O:15][CH2:16][CH3:17])=[O:14])=[C:1]([CH3:2])[C:4]2[C:9](=[CH:8][C:7]([C:19]([F:22])([F:21])[F:20])=[CH:6][N:5]=2)[N:10]=1
Reactant: CCOC(=O)CC(=O)Nc1cc(C(F)(F)F)cnc1C(C)=O
Agent: [H-]
Agent: [Na+]
Solvent: CCO
Product: CCOC(=O)c1c(O)nc2cc(C(F)(F)F)cnc2c1C
Temperature: 25 °C
Reaction time: 1 h
Yield: 82.5 %

Procedure:
To a cooled (ice water batch) suspension of ethyl 3-(2-acetyl-5-(trifluoromethyl)pyridin-3-ylamino)-3-oxopropanoate (1.35 g, 4.24 mmol, 1 eq.) in ethanol (15 ml) was added NaH (60% w/w suspension in oil, 0.19 g, 4.66 mmol, 1.1 eq.) portion wise. The reaction mixture was stirred at RT for 1 h. Then the reaction was quenched with water (20 ml) and ethanol was distilled off. The residue was acidified with 5M aq. HCl (pH˜4) and was extracted with EtOAc (3×100 ml). The combined organic layers were washed with brine (100 ml), dried over anhydrous Na2SO4 and evaporated to provide the crude product, which was triturated with DCM (2×30 ml) to yield ethyl 2-hydroxy-4-methyl-7-(trifluoromethyl)-1,5-naphthyridine-3-carboxylate (1.05 g, 3.50 mmol, 82%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[C:7]([O:9][CH3:10])[CH:6]=[CH:5][C:4]=1[C:11]1([O:41][C@H:40]([CH2:42][O:43][CH2:44][C:45]2[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=2)[C@@H:31]([O:32][CH2:33][C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[C@H:22]([O:23][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C@H:13]1[O:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)O.C([SiH](CC)CC)C.C(=O)([O-])[O-].[K+].[K+].O>C(#N)C>[CH2:15]([O:14][C@@H:13]1[C@@H:22]([O:23][CH2:24][C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=2)[C@H:31]([O:32][CH2:33][C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[C@@H:40]([CH2:42][O:43][CH2:44][C:45]2[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=2)[O:41][C@H:11]1[C:4]1[CH:5]=[CH:6][C:7]([O:9][CH3:10])=[CH:8][C:3]=1[O:2][CH3:1])[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1
Reactant: COc1ccc(C2(O)O[C@H](COCc3ccccc3)[C@@H](OCc3ccccc3)[C@H](OCc3ccccc3)[C@H]2OCc2ccccc2)c(OC)c1
Agent: CC[SiH](CC)CC
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CC#N
Product: COc1ccc([C@@H]2O[C@H](COCc3ccccc3)[C@@H](OCc3ccccc3)[C@H](OCc3ccccc3)[C@H]2OCc2ccccc2)c(OC)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 66.3 %

Procedure:
To a solution of 1-(2,4-dimethoxyphenyl)-2,3,4,6-tetra-O-benzyl-D-glucopyranose (1.7 g) and triethylsilane (0.59 g) in acetonitrile (20 mL) was added boron trifluoride diethyl ether complex (0.40 g) under ice-cooling, and the mixture was warmed to room temperature and stirred overnight. A saturated potassium carbonate aqueous solution was added to the reaction mixture, and the mixture was stirred for 30 minutes. The mixture was poured into water, and the mixture was extracted with diethyl ether. The organic layer washed with water and brine and dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=6/1) to give the title compound (1.1 g).
Reaction SMILES: [Si:1]([O:8][CH2:9][C:10]1[CH:15]=[C:14]([C:16]([F:19])([F:18])[F:17])[CH:13]=[CH:12][C:11]=1[C:20]([CH:22]1[CH2:26][CH2:25][CH2:24][CH2:23]1)=[O:21])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[BH4-].[Na+]>CO>[Si:1]([O:8][CH2:9][C:10]1[CH:15]=[C:14]([C:16]([F:18])([F:19])[F:17])[CH:13]=[CH:12][C:11]=1[CH:20]([CH:22]1[CH2:23][CH2:24][CH2:25][CH2:26]1)[OH:21])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]
Reactant: CC(C)(C)[Si](C)(C)OCc1cc(C(F)(F)F)ccc1C(=O)C1CCCC1
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Product: CC(C)(C)[Si](C)(C)OCc1cc(C(F)(F)F)ccc1C(O)C1CCCC1
Temperature: 25 °C
Reaction time: 8 h
Yield: 93.2 %

Procedure:
To a solution of (2-((tert-butyldimethylsilyloxy)methyl)-4-(trifluoromethyl)-phenyl)-(cyclopentyl)-methanone (138 mg, 0.35 mmol) in methanol (0.5 mL) at room temperature was added sodium borohydride (40.5 mg, 1.07 mmol). The mixture was stirred at room temperature overnight. Methanol was removed in vacuo. The residue was partitioned between ethyl acetate and water. The organic layer was washed with brine, dried over sodium sulfate and concentrated in vacuo to yield the title compound (126.8 mg, 91%). 1H NMR (400 MHz, CDCl3) δ ppm 0.13 (s, 3H) 0.14 (s, 3H) 0.94 (s, 9H) 1.04-1.12 (m, 1H) 1.43-1.74 (m, 6H) 1.87-1.97 (m, 1H) 2.30-2.44 (m, 1H) 2.62-2.75 (m, J=1.66 Hz, 1H) 4.64 (d, J=8.71 Hz, 1H) 4.77 (d, J=12.86 Hz, 1H) 4.92 (d, J=12.86 Hz, 1H) 7.55 (s, 2H) 7.66 (s, 1H).
Reaction SMILES: [CH3:1][S:2]([CH2:5][CH2:6][CH2:7][O:8][C:9]1[CH:10]=[C:11]2[C:15](=[C:16]([NH:18][S:19]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=3)(=[O:21])=[O:20])[CH:17]=1)[NH:14][C:13]([C:28]([O:30][CH2:31][CH3:32])=[O:29])=[CH:12]2)(=[O:4])=[O:3].[C:33](=O)([O-])[O-].[K+].[K+].CN(C)C=O.CI>O>[CH3:33][N:18]([S:19]([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=1)(=[O:21])=[O:20])[C:16]1[CH:17]=[C:9]([O:8][CH2:7][CH2:6][CH2:5][S:2]([CH3:1])(=[O:4])=[O:3])[CH:10]=[C:11]2[C:15]=1[NH:14][C:13]([C:28]([O:30][CH2:31][CH3:32])=[O:29])=[CH:12]2
Reactant: O=C([O-])[O-]
Reactant: CCOC(=O)c1cc2cc(OCCCS(C)(=O)=O)cc(NS(=O)(=O)c3ccccn3)c2[nH]1
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Solvent: CI
Product: CCOC(=O)c1cc2cc(OCCCS(C)(=O)=O)cc(N(C)S(=O)(=O)c3ccccn3)c2[nH]1
Temperature: 25 °C
Reaction time: 15 h
Yield: 75 %

Procedure:
To a mixture of ethyl 5-[3-(methylsulfonyl)propoxy]-7-[(pyridin-2-ylsulfonyl)amino]-1H-indole-2-carboxylate (3.50 g), potassium carbonate (1.01 g) and N,N-dimethylformamide (50 mL) was added methyl iodide (1.14 g) at 0° C., and the reaction mixture was stirred at room temperature for 15 hr. Water was added to the reaction mixture, and the mixture was extracted with a mixed solvent of ethyl acetate-tetrahydrofuran. The organic layer was washed with saturated brine, dried (MgSO4), and concentrated. The obtained residue was subjected to basic silica gel column chromatography, and eluted with hexane-ethyl acetate (1:1-1:4, volume ratio) to give the title compound (2.70 g, yield 75%) as colorless crystals. The crystals were recrystallized from ethyl acetate-hexane to give colorless prism crystals. melting point 176-177° C.
Reaction SMILES: [NH2:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][C:3]=1[Br:10].P([O-])(OCC)(SCC)=[S:12].Cl>C(O)C>[NH2:1][C:2]1[CH:9]=[CH:8][C:5]([C:6](=[S:12])[NH2:7])=[CH:4][C:3]=1[Br:10]
Reactant: N#Cc1ccc(N)c(Br)c1
Reactant: CCOP([O-])(=S)SCC
Agent: Cl
Solvent: CCO
Product: NC(=S)c1ccc(N)c(Br)c1
Temperature: 25 °C
Reaction time: 12 h
Yield: 12.6 %

Procedure:
A stirred solution of 4-amino-3-bromobenzonitrile (6.92 g, 35.1 mmol) and diethyl dithiophosphate (17.7 mL, 105 mmol, 3 eq.) in absolute ethanol (160 mL) at 0° C. was perfused with hydrogen chloride gas at a moderate rate for 30 minutes. The resulting reaction mixture was stirred at room temperature for 12 hours, and then solvent was removed via evaporation under reduced pressure. The residue was suspended in a saturated solution of sodium hydrogen carbonate (25 mL), and this aqueous mixture was extracted with ethyl acetate (3×25 mL). The organic extracts were combined, dried (MgSO4), and evaporated under reduced pressure. The residue was chromatographed using silica gel (approximately 300 g) and elution with an acetone gradient in methylene chloride [1:50 to 1:20] to afford the title compound (1.02 g, 25%) as an amorphous yellow solid: 1H NMR (DMSO-d6) δ 9.41 (br s, NH), 9.13 (br s, NH), 9.13 (br s, NH), 8.11 (d, J=2.1 Hz, 1H), 7.78 (dd, J=2.1 and 8.6 Hz, 1H), 6.72 (d, J=8.7 Hz, 1H), 6.03 (s, 2NH); TLC: RB1 =0.15[1% diethyl ether in methylene chloride].
Reaction SMILES: [C:1]([NH2:20])(=[O:19])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8]/[CH:9]=[CH:10]\[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18].C(N)(=O)CCCCCCCCCCC/C=C\CCCCCCCC>>[C:1]([NH2:20])(=[O:19])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18]
Reactant: CCCCCCCC/C=C\CCCCCCCC(N)=O
Agent: CCCCCCCC/C=C\CCCCCCCCCCCC(N)=O
Product: CCCCCCCCCCCCCCCCCC(N)=O

Procedure:
Oleic acid amide lubricant ##STR1## "ALFLOW E-10" (Nippon Oil and Fats Co., Ltd.) Erucic acid amide lubricant ##STR2## "ALFLOW P-10" (Nippon Oil and Fats Co., Ltd.)
Reaction SMILES: C(OC(=O)[N:7]([CH3:25])[C:8]1[C:9]2[N:10]([C:14]([C:17]3[CH:22]=[CH:21][N:20]=[C:19](SC)[N:18]=3)=[CH:15][N:16]=2)[CH:11]=[CH:12][N:13]=1)(C)(C)C.[CH3:27][NH2:28]>>[CH3:25][NH:7][C:8]1[C:9]2[N:10]([C:14]([C:17]3[CH:22]=[CH:21][N:20]=[C:19]([NH:28][CH3:27])[N:18]=3)=[CH:15][N:16]=2)[CH:11]=[CH:12][N:13]=1
Reactant: CN
Reactant: CSc1nccc(-c2cnc3c(N(C)C(=O)OC(C)(C)C)nccn23)n1
Product: CNc1nccc(-c2cnc3c(NC)nccn23)n1

Procedure:
Methyl-[3-(2-methylamino-pyrimidin-4-yl)-imidazo[1,2-a]pyrazin-8-yl]-amine was prepared by a process analogous to that described in Example 12 starting from methyl-[3-(2-methylsulfanyl-pyrimidin-4-yl)-imidazo[1,2-a]pyrazin-8-yl]-carbamic acid tert-butyl ester (from Example 8 supra), and methylamine LC-MS: [M+H]+ 256.2.
Reaction SMILES: [CH3:1][S:2]([C:5]1[CH:10]=[CH:9][C:8]([C:11]([C:19]2[NH:29][C:22]3=[N:23][CH:24]=[C:25]([O:27][CH3:28])[CH:26]=[C:21]3[CH:20]=2)=[CH:12][CH:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)=[CH:7][CH:6]=1)(=[O:4])=[O:3]>[Pd].CO>[CH3:1][S:2]([C:5]1[CH:6]=[CH:7][C:8]([CH:11]([C:19]2[NH:29][C:22]3=[N:23][CH:24]=[C:25]([O:27][CH3:28])[CH:26]=[C:21]3[CH:20]=2)[CH2:12][CH:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)=[CH:9][CH:10]=1)(=[O:3])=[O:4]
Reactant: COc1cnc2[nH]c(C(=CC3CCOCC3)c3ccc(S(C)(=O)=O)cc3)cc2c1
Agent: [Pd]
Solvent: CO
Product: COc1cnc2[nH]c(C(CC3CCOCC3)c3ccc(S(C)(=O)=O)cc3)cc2c1
Temperature: 50 °C
Yield: 43.9 %

Procedure:
A mixture of 2-[1-(4-methanesulfonyl-phenyl)-2-(tetrahydro-pyran-4-yl)-vinyl]-5-methoxy-1H-pyrrolo[2,3-b]pyridine (180 mg, 0.44 mmol) and 10% palladium on activated carbon (50 mg) in methanol (200 mL) was heated at 50° C. under hydrogen (50 psi) for 6 h. The mixture was cooled to room temperature. The catalyst was removed by filtration and washed with ethyl acetate. The filtrate was concentrated in vacuo and purified using a Waters automated flash system (column: Xterra 30 mm×100 mm, sample manager 2767, pump 2525, detector: ZQ mass and UV 2487, solvent system: acetonitrile and 0.1% ammonium hydroxide in water) to afford 2-[1-(4-methanesulfonyl-phenyl)-2-(tetrahydro-pyran-4-yl)-ethyl]-5-methoxy-1H-pyrrolo[2,3-b]pyridine (80 mg, 44.4%) as a white solid: LC/MS m/e calcd for C22H26N2O4S [M+H]+ 415.53, observed 415.2; 1H NMR (400 MHz, CD3OD) δ ppm 7.84-7.92 (m, 3H), 7.61 (d, J=8.3 Hz, 2H), 7.50 (d, J=2.5 Hz, 1H), 6.34 (s, 1H), 4.42 (t, J=8.0 Hz, 1H), 3.84-3.93 (m, 5H), 3.32-3.26 (m, 2H), 3.09 (s, 3H), 2.18-2.27 (m, 1H), 1.97-2.05 (m, 1H), 1.69-1.76 (m, 2H), 1.50 (ddt, J=10.8, 7.1, 3.5 Hz, 1H), 1.31-1.42 (m, 2H).
Reaction SMILES: [C:1]([C:3]1[CH:4]=[C:5]([CH:8]=[CH:9][CH:10]=1)[CH:6]=O)#[N:2].[CH3:11][C:12](=[O:17])[CH2:13][C:14](=[O:16])[CH3:15].C([O-])(=O)C.[NH4+]>CC(O)C>[C:1]([C:3]1[CH:4]=[C:5]([CH:8]=[CH:9][CH:10]=1)[CH:6]=[C:13]([C:12](=[O:17])[CH3:11])[C:14](=[O:16])[CH3:15])#[N:2]
Reactant: CC(=O)CC(C)=O
Reactant: N#Cc1cccc(C=O)c1
Agent: CC(=O)[O-]
Agent: [NH4+]
Solvent: CC(C)O
Product: CC(=O)C(=Cc1cccc(C#N)c1)C(C)=O

Procedure:
3-cyanobenzaldehyde (2,62 g) was condenced with 2,4-pentanedione (3,0 g) in 2-propanol (10 ml) in the presence of ammonium acetate. Mp 63°-64° C., yield 1,27 g (30%).