Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: BrC(CC1NC=NC=1)C(O)=O.SC[CH:14]([NH2:22])[CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.[C:23](=[O:26])([O-])[O-:24].[Na+].[Na+].SCCN>>[NH2:22][C@H:14]([C:23]([OH:24])=[O:26])[CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1
Reactant: O=C([O-])[O-]
Reactant: NC(CS)Cc1ccccc1
Agent: NCCS
Agent: O=C(O)C(Br)Cc1cnc[nH]1
Agent: [Na+]
Product: N[C@@H](Cc1ccccc1)C(=O)O

Procedure:
This product is prepared from α-bromo-β-(5-imidazolyl) propionic acid and 2-mercapto-1-benzyl-ethylamine by reaction in the presence of sodium carbonate utilizing the procedure described for the analogous reaction involving 2-mercaptoethylamine as described in Example 1.
Reaction SMILES: CO[C:3](OC)([N:5]([CH3:7])[CH3:6])[CH3:4].[C:10]([O:14][C:15](=[O:22])[NH:16][CH2:17][CH2:18][C:19](=[S:21])[NH2:20])([CH3:13])([CH3:12])[CH3:11]>C(Cl)Cl>[C:10]([O:14][C:15](=[O:22])[NH:16][CH2:17][CH2:18][C:19](=[S:21])[N:20]=[C:3]([N:5]([CH3:7])[CH3:6])[CH3:4])([CH3:13])([CH3:11])[CH3:12]
Reactant: COC(C)(OC)N(C)C
Reactant: CC(C)(C)OC(=O)NCCC(N)=S
Solvent: ClCCl
Product: CC(=NC(=S)CCNC(=O)OC(C)(C)C)N(C)C
Temperature: 25 °C
Reaction time: 24 h

Procedure:
Dimethylacetamide dimethylacetal (1.56 g, 11.7 mmol) is added to a stirred solution of (2-thiocarbamoyl-ethyl)-carbamic acid tert-butyl ester (1.0 g, 4.9 mmol) in DCM (50 ml). The reaction is stirred for 24 hours at room temperature followed by removal of the solvent. The residue is purified by chromatography on silica, eluting with ethyl acetate-diethyl ether (1:1) to give the titled compound as a yellow oil.
Reaction SMILES: Br[C:2]1[CH:8]=[C:7]([CH2:9][CH:10]2[CH2:14][CH2:13][CH2:12][CH2:11]2)[CH:6]=[CH:5][C:3]=1[NH2:4].[Cl:15][C:16]1[C:21]([Cl:22])=[CH:20][CH:19]=[CH:18][C:17]=1B(O)O>>[Cl:15][C:16]1[C:21]([Cl:22])=[CH:20][CH:19]=[CH:18][C:17]=1[C:2]1[CH:8]=[C:7]([CH2:9][CH:10]2[CH2:14][CH2:13][CH2:12][CH2:11]2)[CH:6]=[CH:5][C:3]=1[NH2:4]
Reactant: Nc1ccc(CC2CCCC2)cc1Br
Reactant: OB(O)c1cccc(Cl)c1Cl
Product: Nc1ccc(CC2CCCC2)cc1-c1cccc(Cl)c1Cl

Procedure:
2-bromo-4-(cyclopentylmethyl)aniline and 2,3-dichlorobenzene boronic acid can be combined to form 2-(2,3-dichlorophenyl)-4-(cyclopentylmethyl)aniline, and
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([O:15][CH3:16])[C:10]=1Br)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([Li])CCC.C[O:24][B:25](OC)[O:26]C>C1COCC1>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([O:15][CH3:16])[C:10]=1[B:25]([OH:26])[OH:24])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: COc1cccc(OCc2ccccc2)c1Br
Reactant: COB(OC)OC
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: COc1cccc(OCc2ccccc2)c1B(O)O
Temperature: -78 °C
Reaction time: 0.5 h
Yield: 45.7 %

Procedure:
To a mixture of 1-(benzyloxy)-2-bromo-3-methoxybenzene (2.66 g, 9.07 mmol) in THF (20 mL) was added butyllithium (2.5 M in THF, 4 mL, 9.98 mmol) at −78° C. dropwise over 15 minutes. The mixture was stirred at −78° C. for 30 minutes, then trimethylborate (4.0 mL, 36.3 mmol) was added. The mixture was allowed to warm to RT and stirred overnight. The mixture was quenched with 1 M aqueous HCl to pH 2 and extracted with DCM. The organic phase was dried over Na2SO4 and concentrated in vacuo. The residue was purified by flash column chromatography (EtOAc/Heptane) to afford the desired product as a white solid (1.07 g, 46% yield). MS (M+1)=259.4.
Reaction SMILES: [NH2:1][C@@H:2]([C:10]([NH2:12])=[O:11])[CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[CH2:13]1[CH2:19][S:16](=[O:18])(=[O:17])[O:15][CH2:14]1>C(#N)C>[C:10]([C@H:2]([NH:1][CH2:14][CH2:13][CH2:19][S:16]([OH:18])(=[O:17])=[O:15])[CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)(=[O:11])[NH2:12]
Reactant: O=S1(=O)CCCO1
Reactant: NC(=O)[C@H](N)Cc1ccccc1
Solvent: CC#N
Product: NC(=O)[C@@H](Cc1ccccc1)NCCCS(=O)(=O)O
Temperature: 25 °C
Yield: 86.3 %

Procedure:
To a solution of D-Phenylalaninamide (1.83 g, 11.1 mmol) in acetonitrile (20 mL) was added 1,3-propane sultone (1.29 g, 10.6 mmol). The solution was stirred at reflux for 2.5 hours. The reaction mixture was cooled to room temperature. The solid was filtered and washed with acetonitrile (2×20 mL). The solid product was suspended in EtOH (75 mL). The suspension was stirred at reflux for 1 hours. The solid material was filtered, washed with acetone (1×25 mL) and dried in vacuo, affording the title compound (2.62 g, 89%). 1H NMR (D2O, 500 MHz) δ ppm 7.28 (m, 3H), 7.19 (m, 2H), 4.05 (m, 1H), 3.19 (dd, 1H, J=5.3 Hz, 14.2 Hz), 3.04 (m, 3H), 2.86 (t, 2H, J=5.8 Hz), 2.03 (m, 2H). 13C (D2O, 125 MHz) δ ppm 170.39, 133.73, 129.62, 129.26, 128.15, 61.57, 47.99, 45.57, 36.21, 21.45. [α]D=−20.7° (c=0.0038 in water), ES-MS 285 (M−1).
Reaction SMILES: Br[CH2:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:13]=[C:12]([C:14]([NH2:16])=[O:15])[O:11][N:10]=2)=[CH:5][CH:4]=1.[CH:17]1[C:22]([OH:23])=[CH:21][CH:20]=[CH:19][C:18]=1[CH3:24].C([O-])([O-])=O.[K+].[K+]>CC#N>[C:18]1([CH3:24])[CH:19]=[CH:20][CH:21]=[C:22]([O:23][CH2:2][C:3]2[CH:8]=[CH:7][C:6]([C:9]3[CH:13]=[C:12]([C:14]([NH2:16])=[O:15])[O:11][N:10]=3)=[CH:5][CH:4]=2)[CH:17]=1
Reactant: NC(=O)c1cc(-c2ccc(CBr)cc2)no1
Reactant: Cc1cccc(O)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: Cc1cccc(OCc2ccc(-c3cc(C(N)=O)on3)cc2)c1
Temperature: 90 °C
Yield: 60.6 %

Procedure:
To a mixture of 3-(4-bromomethyl-phenyl)-isoxazole-5-carboxylic acid amide (which may be prepared as described in Preparation of Intermediate 14; 30 mg, 0.107 mmol) in CH3CN (2 mL) were added m-cresol (20 mg, 0.185 mmol) and K2CO3 (30 mg, 0.22 mmol). The mixture was heated at 90° C. for 16 h and then evaporated to dryness. The residue was purified by chromatography (66-75% EtOAc/hexanes) to give 3-(4-m-tolyloxymethyl-phenyl)-isoxazole-5-carboxylic acid amide (20 mg, 61%) as a white powder. 1H NMR (300 MHz, DMSO-d6) δ ppm 8.38 (br. s., 1H), 8.00 (br. s., 1H), 7.86-7.95 (m, 3H), 7.53-7.63 (m, 4H), 7.11-7.22 (m, 1H), 6.69-6.89 (m, 3H), 5.15 (s, 2H), 2.26 (s, 3H).
Reaction SMILES: [CH3:1][O:2][C:3]1[C:4]([O:16][CH2:17][CH2:18][CH2:19][Br:20])=[CH:5][C:6]([N+:13]([O-])=O)=[C:7]([CH:12]=1)[C:8]([O:10][CH3:11])=[O:9].[H][H]>[Pd].CO>[CH3:1][O:2][C:3]1[CH:12]=[C:7]([C:8]([O:10][CH3:11])=[O:9])[C:6]([NH2:13])=[CH:5][C:4]=1[O:16][CH2:17][CH2:18][CH2:19][Br:20]
Reactant: [H][H]
Reactant: COC(=O)c1cc(OC)c(OCCCBr)cc1[N+](=O)[O-]
Agent: [Pd]
Solvent: CO
Product: COC(=O)c1cc(OC)c(OCCCBr)cc1N
Temperature: 40 °C
Yield: 100 %

Procedure:
In a 50 mL volume glass flask equipped with a stirrer, a thermometer, a reflux condenser and a gas inlet were placed 2.02 g (5.75 mmol) of methyl 5-methoxy-4-(3-bromopropoxy)-2-nitrobenzoate (purity: 99%) obtained in Reference Example III-6 and 40 mL of methanol. The resulting mixture was heated to 40° C. under stirring. To the mixture was added 0.2 g of 5 wt. % palladium/carbon (containing 49% water). The resulting mixture was heated to the same temperature for 2 hours, while hydrogen was introduced to the mixture under atmospheric pressure at a rate of 50 mL/min. After the reaction was complete, the reaction mixture was filtered. The filtrate was concentrated under reduced pressure, precipitating a crystalline product. The crystalline product was dried under reduce pressure, to give 1.83 g (isolated yield: 98.1%, purity: 98% in terms of area percentage determined by high performance liquid chromatography) of methyl 5-methoxy-4-(3-bromopropoxy)anthranilate.
Reaction SMILES: FC1C=CC(CCC(C2C=CC=CC=2)=O)=CC=1.[F:18][C:19]1[CH:24]=[CH:23][C:22]([CH2:25][CH2:26]/[C:27](/[C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)=[CH:28]/[C:29]([O:31][CH2:32][CH3:33])=[O:30])=[CH:21][CH:20]=1>>[F:18][C:19]1[CH:20]=[CH:21][C:22]([CH2:25][CH2:26]/[C:27](/[C:34]2[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=2)=[CH:28]\[C:29]([O:31][CH2:32][CH3:33])=[O:30])=[CH:23][CH:24]=1
Reactant: CCOC(=O)/C=C(/CCc1ccc(F)cc1)c1ccccc1
Agent: O=C(CCc1ccc(F)cc1)c1ccccc1
Product: CCOC(=O)/C=C(\CCc1ccc(F)cc1)c1ccccc1

Procedure:
By a procedure similar to that of example 1.85.3, starting from 3-(4-fluorophenyl)-1-phenylpropan-1-one, (Z)-ethyl 5-(4-fluorophenyl)-3-phenylpent-2-enoate and (E)-ethyl 5-(4-fluorophenyl)-3-phenylpent-2-enoate were obtained as colourless oils.
Reaction SMILES: [C:1]([O:4][CH2:5][C:6]1[C:11]([N:12]2[CH2:24][CH2:23][N:15]3[C:16]4[CH2:17][CH2:18][CH2:19][CH2:20][C:21]=4[CH:22]=[C:14]3[C:13]2=[O:25])=[CH:10][C:9]([F:26])=[CH:8][C:7]=1[C:27]1[CH:32]=[C:31]([NH:33][C:34]2[CH:39]=[CH:38][C:37]([N:40]3[CH2:45][CH2:44][N:43]([CH3:46])[CH2:42][C@H:41]3[CH3:47])=[CH:36][N:35]=2)[C:30](=[O:48])[N:29]([CH3:49])[CH:28]=1)(=[O:3])[CH3:2].BrC1C=C(NC2C=CC(N3CCN(C)C[C@@H]3C)=CN=2)C(=O)N(C)C=1.C(OCC1C(B2OC(C)(C)C(C)(C)O2)=CC(F)=CC=1N1CCN2C3CCCCC=3C=C2C1=O)(=O)C>>[C:1]([O:4][CH2:5][C:6]1[C:11]([N:12]2[CH2:24][CH2:23][N:15]3[C:16]4[CH2:17][CH2:18][CH2:19][CH2:20][C:21]=4[CH:22]=[C:14]3[C:13]2=[O:25])=[CH:10][C:9]([F:26])=[CH:8][C:7]=1[C:27]1[CH:32]=[C:31]([NH:33][C:34]2[CH:39]=[CH:38][C:37]([N:40]3[CH2:45][CH2:44][N:43]([CH3:46])[CH2:42][C@@H:41]3[CH3:47])=[CH:36][N:35]=2)[C:30](=[O:48])[N:29]([CH3:49])[CH:28]=1)(=[O:3])[CH3:2]
Reactant: CC(=O)OCc1c(-c2cc(Nc3ccc(N4CCN(C)C[C@H]4C)cn3)c(=O)n(C)c2)cc(F)cc1N1CCn2c(cc3c2CCCC3)C1=O
Agent: CC(=O)OCc1c(B2OC(C)(C)C(C)(C)O2)cc(F)cc1N1CCn2c(cc3c2CCCC3)C1=O
Agent: C[C@H]1CN(C)CCN1c1ccc(Nc2cc(Br)cn(C)c2=O)nc1
Product: CC(=O)OCc1c(-c2cc(Nc3ccc(N4CCN(C)C[C@@H]4C)cn3)c(=O)n(C)c2)cc(F)cc1N1CCn2c(cc3c2CCCC3)C1=O
Yield: 50 %

Procedure:
Following the procedures as described for compound 109f, 110a (391 mg, 1 mmol) and 4-fluoro-2-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl acetate (482 mg, 1 mmol) were coupled by Suzuki reaction to give 110b as a white solid (334 mg, 50%). LCMS: [M+H]+ 668
Reaction SMILES: Cl[CH2:2][CH2:3][C@H:4]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)[OH:5].[I-].[Na+].C(O)(C)C.O.O.[C:20]([OH:25])(=[O:24])[C:21]([OH:23])=[O:22].[CH3:26][NH2:27]>C(O)C>[C:20]([OH:25])(=[O:24])[C:21]([OH:23])=[O:22].[CH3:26][NH:27][CH2:2][CH2:3][C@@H:4]([OH:5])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.[CH3:26][NH:27][CH2:2][CH2:3][C@H:4]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)[OH:5]
Reactant: O[C@H](CCCl)c1ccccc1
Reactant: CN
Agent: O=C(O)C(=O)O
Agent: [I-]
Agent: [Na+]
Solvent: CC(C)O
Solvent: CCO
Solvent: O
Product: CNCC[C@@H](O)c1ccccc1
Temperature: 25 °C

Procedure:
A solution of (R)-3-chloro-1-phenylpropanol (1.0 g, 5.85 mmol) and a catalytic amount of sodium iodide in ethanol (7 mL) and 40% methylamine aqueous solution (15 mL) was stirred at 60° C. for 7 hours. The reaction mixture was evaporated to 3 mL, and the pH of the solution was adjusted to pH>12 via the addition of aqueous NaOH solution. The mixture was then extracted with toluene twice and the combined extracts were washed with brine. The toluene layer was evaporated to dryness and the residue dissolved in toluene (5 mL) and isopropanol (5.mL) and oxalic acid dihydrate (0.4 g, 3.2 mmol) was added. It was stirred at room temperature for 2Hours and the suspension was filtered and rinsed with toluene/isopropanol to provide 0.9 g of (R)—N-methyl-3-hydroxy-3-phenylpropylamine hemioxalate salt as an off-white solid. 1H NMR (D2O) δ 7.5-7.2 (m, 5H), 4.8 (at, J=6.6 Hz, 1H), 5.15-2.9 (m, 2H), 2.64 (s, 3H), 2.2-2.0 (m, 2H). Elemental Analysis for C11H16NO3; Calculated: H 7.67%; C 62.84%; N 6.66%.
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].[C:7]([O:11][C:12]([NH:14][C@@:15]1([C:50]([O:52][C:53]([CH3:56])([CH3:55])[CH3:54])=[O:51])[C@H:20]([O:21][CH2:22][C:23]2[CH:28]=[CH:27][C:26]([Cl:29])=[C:25]([Cl:30])[CH:24]=2)[C@@H:19]([O:31]C(C2C=CC([N+]([O-])=O)=CC=2)=O)[C@@H:18]2[C@H:16]1[C@H:17]2[C:43]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44])=[O:13])([CH3:10])([CH3:9])[CH3:8]>CO>[C:7]([O:11][C:12]([NH:14][C@@:15]1([C:50]([O:52][C:53]([CH3:56])([CH3:55])[CH3:54])=[O:51])[C@H:20]([O:21][CH2:22][C:23]2[CH:28]=[CH:27][C:26]([Cl:29])=[C:25]([Cl:30])[CH:24]=2)[C@@H:19]([OH:31])[C@@H:18]2[C@H:16]1[C@H:17]2[C:43]([O:45][C:46]([CH3:48])([CH3:47])[CH3:49])=[O:44])=[O:13])([CH3:10])([CH3:8])[CH3:9]
Reactant: CC(C)(C)OC(=O)N[C@]1(C(=O)OC(C)(C)C)[C@@H]2[C@@H](C(=O)OC(C)(C)C)[C@@H]2[C@H](OC(=O)c2ccc([N+](=O)[O-])cc2)[C@H]1OCc1ccc(Cl)c(Cl)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Product: CC(C)(C)OC(=O)N[C@]1(C(=O)OC(C)(C)C)[C@@H]2[C@@H](C(=O)OC(C)(C)C)[C@@H]2[C@H](O)[C@H]1OCc1ccc(Cl)c(Cl)c1
Reaction time: 16 h
Yield: 98.7 %

Procedure:
Potassium carbonate (153.45 g, 1.11 mol) is added to a suspension of di-tert-butyl (1S,2R,3S,4S,5R,6R)-2-[(tert-butoxycarbonyl)amino]-3-[(3,4-dichlorobenzyl)oxy]-4-{[(4-nitrophenyl)carbonyl]oxy}bicyclo[3.1.0]hexane-2,6-dicarboxylate (273.00 g, 370.11 mmol) in methanol (3.28 L) at ambient temperature. After 16 hours, the reaction is concentrated in vacuo. The residue is dissolved in methyl tert-butyl ether (2 L), and washed subsequently with water (0.8 L), brine (0.8 L), dried over MgSO4, and concentrated in vacuo to yield the title compound as a white solid (215 g, 98% yield).
Reaction SMILES: C(OC([N:11]1[CH2:16][CH2:15][CH:14]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=2[O:23][CH3:24])[CH2:13][CH2:12]1)=O)C1C=CC=CC=1.C1CCCCC=1>C(O)C.[Pd].CCOCC>[CH3:24][O:23][C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=1[CH:14]1[CH2:15][CH2:16][NH:11][CH2:12][CH2:13]1
Reactant: COc1ccccc1C1CCN(C(=O)OCc2ccccc2)CC1
Agent: [Pd]
Solvent: C1=CCCCC1
Solvent: CCO
Solvent: CCOCC
Product: COc1ccccc1C1CCNCC1
Temperature: 25 °C
Yield: 50.8 %

Procedure:
A solution of 1-benzyloxycarbonyl-4-(2-methoxyphenyl)piperidine (0.67 g) in ethanol (10 mL) was treated with cyclohexene (4.2 mL) followed by 10% palladium on carbon (0.13 g). After heating to reflux for 2 hours, the reaction mixture was cooled to room temperature, diluted with ether and extracted with 1N hydrochloric acid. The aqueous layer was made basic with sodium bicarbonate and extracted with dichloromethane. The organic layers were dried over anhydrous sodium sulfate and evaporated to afford the piperidine (0.2 g); NMR (CDCl3): 1.60 (d of q, 2, J1 =12, J2 =4), 1.73-1.82 (broad, 2), 2.74-2.83 (d of t, 2, J1 =12, J2 =2), 3.02-3.2 (m, 3), 3.82 (s, 3), 6.85 (d, 1, J=8), 6.9 (m, 1), 7.15-7.26 (m, 2); MS: m/z=192(M+1). This material was used in the next step without further purification.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]([CH2:13][C:14]([F:17])([F:16])[F:15])[CH2:9][C:10](O)=[O:11])=[C:4]([C:18]([F:21])([F:20])[F:19])[CH:3]=1.B.C1COCC1>C1COCC1>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]([CH2:13][C:14]([F:16])([F:17])[F:15])[CH2:9][CH2:10][OH:11])=[C:4]([C:18]([F:19])([F:20])[F:21])[CH:3]=1
Reactant: O=C(O)CN(CC(F)(F)F)c1ccc(Br)cc1C(F)(F)F
Agent: B
Solvent: C1CCOC1
Product: OCCN(CC(F)(F)F)c1ccc(Br)cc1C(F)(F)F
Temperature: 25 °C
Reaction time: 0.05 h
Yield: 80.9 %

Procedure:
To a solution of N-[4-bromo-2-(trifluoromethyl)phenyl]-N-(2,2,2-trifluoroethyl)glycine (1.50 g, 3.95 mmol) in dry THF (10 mL) at 0° C., under N2, was added a solution of BH3/THF in THF (6.6 mL, 1.8 M, 12 mmol), dropwise over 3 min. The cooling bath was removed and the mixture was stirred at rt. After 23 h, an additional portion of BH3/THF (2.2 mL, 4 mmol) was added and stirring was continued another 6 h. The mixture was cooled to 0° C., quenched by dropwise addition of 10% v/v HCl and poured into water and extracted with EtOAc (×3). Combined organic portions were washed (water, brine), dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by flash chromatography (EtOAc/hexanes), affording 1.17 g of the title compound as a colorless syrup: 1H NMR (300 MHz, CD3OD) δ 7.81-7.73 (m, 2H), 7.55 (d, J=8.2 Hz, 1H), 3.89 (q, J=9.3 Hz, 2H), 3.61 (t, J=6.2 Hz, 2H), 3.24 (t, J=6.1 Hz, 2H).
Reaction SMILES: [H-].[H-].[H-].[H-].[Li+].[Al+3].[CH3:7][O:8][C:9]1[CH:10]=[C:11]([CH:16]=[C:17]([O:22][CH3:23])[C:18]=1[CH2:19][CH2:20]C)[C:12]([O:14]C)=O.[CH3:24]COCC>>[CH3:23][O:22][C:17]1[CH:16]=[C:11]([CH:10]=[C:9]([O:8][CH3:7])[C:18]=1[CH:19]([CH3:20])[CH3:24])[CH2:12][OH:14]
Reactant: CCOCC
Reactant: CCCc1c(OC)cc(C(=O)OC)cc1OC
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Product: COc1cc(CO)cc(OC)c1C(C)C
Temperature: 0 °C
Reaction time: 1 h
Yield: 88 %

Procedure:
To a suspension of LiAlH4 (95%) (5.00 g, 125 mmol) in dry ether (100 mL) at 0° C. was added a solution of methyl 3,5-dimethoxy-4-1-propylbenzoate (15.7 g, 90.1 mmol), in ether (300 mL) under N2. The suspension was stirred at 0° C. for one hour then for an additional hour at room temperature. The reaction was quenched by slow addition of a saturated Na2SO4 aqueous solution (10 mL) at 0° C. The mixture was stirred overnight. The solid was filtered off and the filtrate was evaporated to dryness to give the desired alcohol (13.8 g, 88% yield) as white crystals. 1HNMR (CDCl3. ppm): δ 1.34 (d, J=7.2 Hz, 6H), 3.65 (hept., J=7.2 Hz, 1H), 3.88 (s, 6H), 4.70 (s, 2H), 6.62 (s, 2H).
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[N:9]=[CH:8][NH:7][N:6]=1)=[O:4].[NH:10]1[C:18]2[C:13](=[CH:14][C:15](B(O)O)=[CH:16][CH:17]=2)[CH:12]=[CH:11]1.N1C=CC=CC=1>C([O-])(=O)C.[Cu+2].C([O-])(=O)C.CN(C)C=O>[CH3:1][O:2][C:3]([C:5]1[N:9]=[CH:8][N:7]([C:15]2[CH:14]=[C:13]3[C:18](=[CH:17][CH:16]=2)[NH:10][CH:11]=[CH:12]3)[N:6]=1)=[O:4]
Reactant: COC(=O)c1nc[nH]n1
Reactant: OB(O)c1ccc2[nH]ccc2c1
Agent: [Cu+2]
Agent: CC(=O)[O-]
Solvent: CN(C)C=O
Solvent: c1ccncc1
Product: COC(=O)c1ncn(-c2ccc3[nH]ccc3c2)n1
Yield: 24.5 %

Procedure:
1H-1,2,4-triazole-3-carboxylic acid methyl ester (1.12 g, 8.79 mmol), 1H-indol-5-ylboronic acid (1.42 g, 8.79 mmol), N,N-dimethylformamide (90 mL), copper (II) acetate (1.20 g, 6.60 mmol) and pyridine (1.40 mL, 17.3 mmol) were reacted according to the same procedure as Preparation 1 to give the title compound (519.7 mg, 2.15 mmol, 24% Yield).
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][CH:4]([C:7]2[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[N:9]([CH2:16][C:17]3[CH:21]=[CH:20][S:19][CH:18]=3)[CH:8]=2)[CH2:3][CH2:2]1.C[O:23][C:24](=[O:33])[C:25]1[CH:30]=[CH:29][CH:28]=[C:27]([CH2:31]Br)[CH:26]=1>>[S:19]1[CH:20]=[CH:21][C:17]([CH2:16][N:9]2[C:10]3[C:15](=[CH:14][CH:13]=[CH:12][CH:11]=3)[C:7]([CH:4]3[CH2:5][CH2:6][N:1]([CH2:31][C:27]4[CH:26]=[C:25]([CH:30]=[CH:29][CH:28]=4)[C:24]([OH:33])=[O:23])[CH2:2][CH2:3]3)=[CH:8]2)=[CH:18]1
Reactant: c1ccc2c(c1)c(C1CCNCC1)cn2Cc1ccsc1
Reactant: COC(=O)c1cccc(CBr)c1
Product: O=C(O)c1cccc(CN2CCC(c3cn(Cc4ccsc4)c4ccccc34)CC2)c1

Procedure:
This compound was prepared following the procedure described in example 117 (part C) starting with 0.1 g (0.38 mmol) of 3-piperidin-4-yl-1-thiophen-3-ylmethyl-1H-indole and 0.1 g (0.48 mmol) of 3-bromomethyl-benzoic acid methyl ester. The crude mixture was purified by HPLC-MS using a C-18 column, and 0.005 g (98% of purity) of the expected acid were isolated.
Reaction SMILES: [N:1]([C:4]1[CH:14]=[CH:13][C:7]([CH:8]=[CH:9][C:10](Cl)=[O:11])=[CH:6][CH:5]=1)=[N+:2]=[N-:3].[CH2:15]([NH:17][N:18]([NH:22][CH2:23][CH3:24])[CH2:19][CH2:20][NH2:21])[CH3:16]>C(Cl)(Cl)Cl>[CH2:15]([NH:17][N:18]([NH:22][CH2:23][CH3:24])[CH2:19][CH2:20][NH:21][C:10](=[O:11])[CH:9]=[CH:8][C:7]1[CH:13]=[CH:14][C:4]([N:1]=[N+:2]=[N-:3])=[CH:5][CH:6]=1)[CH3:16]
Reactant: [N-]=[N+]=Nc1ccc(C=CC(=O)Cl)cc1
Reactant: CCNN(CCN)NCC
Solvent: ClC(Cl)Cl
Product: CCNN(CCNC(=O)C=Cc1ccc(N=[N+]=[N-])cc1)NCC

Procedure:
Subsequently, 8.5 g (40 millimoles) of the p-azidocinnamic acid chloride was dissolved in chloroform, and 4.8 g (40 millimoles) of N,N-diethylaminoethylenediamine was added thereto at a reaction temperature of 10° to 20° C., after which the resulting solution was further allowed to react for 1 hour. The chloroform was distilled off under reduced pressure, and 100 ml of water was added to the resulting oily substance, after which a solution of 1.7 g of sodium hydroxide in 20 ml of water was added thereto on an ice bath. The organic layer separated was extracted with chloroform, and the extract was further washed with water and then dried over anhydrous sodium sulfate. The solvent was distilled off to obtain 11 g of an oily substance as the distillation residue. This oily substance decomposed at 130° C. with formation of bubbles and generation of heat. This oily substance was identified as the compound of this invention by analysis using the following spectral means: ##STR115##
Reaction SMILES: P(Cl)(Cl)(Cl)=O.[CH:6]1([CH2:11][NH:12][C:13](=[O:24])[CH2:14][C:15]2[CH:23]=[C:22]3[C:18]([CH:19]=[CH:20][NH:21]3)=[CH:17][CH:16]=2)[CH2:10][CH2:9][CH2:8][CH2:7]1.[OH-].[Na+].CN(C)[CH:29]=[O:30]>>[CH:6]1([CH2:11][NH:12][C:13](=[O:24])[CH2:14][C:15]2[CH:23]=[C:22]3[C:18]([C:19]([CH:29]=[O:30])=[CH:20][NH:21]3)=[CH:17][CH:16]=2)[CH2:10][CH2:9][CH2:8][CH2:7]1
Reactant: CN(C)C=O
Reactant: O=C(Cc1ccc2cc[nH]c2c1)NCC1CCCC1
Agent: [Na+]
Agent: [OH-]
Solvent: O=P(Cl)(Cl)Cl
Product: O=Cc1c[nH]c2cc(CC(=O)NCC3CCCC3)ccc12
Reaction time: 0.25 h
Yield: 58 %

Procedure:
N,N-dimethylformamide (0.53 ml) was cooled to 0° under an atmosphere of nitrogen and treated with phosphorus oxychloride (0.17 ml). This solution was stirred at 0° for 15 min and treated with a solution of N-cyclopentylmethylindole-6-acetamide (Example 1, part h), (0.40 g) in N,N-dimethylformamide (4 ml). The yellow mixture was stirred for 30 min and then brought to pH 14 by the addition of ice and 20% (w/v) aqueous sodium hydroxide. The mixture was heated to reflux for 5 min and allowed to cool. The precipitate which formed was collected by filtration to give N-cyclopentylmethyl-3-formylindole-6-acetamide (0.26 g, 58%) as a tan powder; partial NMR (80 MHz, DMSO-d6): 2.96(t, 2H, NHCH2), 3.48(s, 2H, COCH2), 7.21(dd, 1H, H5 -indole), 7.38(br s, 1H, H2 -indole), 9.88(s, 1H, CHO).
Reaction SMILES: [C:1]([C:5]1[N:10]=[CH:9][C:8](/[CH:11]=[CH:12]/[C:13]([NH:15][C:16]2[CH:17]=[C:18]3[C:22](=[CH:23][CH:24]=2)[N:21]([CH2:25][CH2:26][O:27][Si](C)(C)C(C)(C)C)[CH:20]=[CH:19]3)=[O:14])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].C(C1N=CC(/C=C/C(O)=O)=CC=1)(C)(C)C.C[Si](C)(OCCN1C2C(=CC(N)=CC=2)C=C1)C(C)(C)C>>[C:1]([C:5]1[N:10]=[CH:9][C:8](/[CH:11]=[CH:12]/[C:13]([NH:15][C:16]2[CH:17]=[C:18]3[C:22](=[CH:23][CH:24]=2)[N:21]([CH2:25][CH2:26][OH:27])[CH:20]=[CH:19]3)=[O:14])=[CH:7][CH:6]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)c1ccc(/C=C/C(=O)Nc2ccc3c(ccn3CCO[Si](C)(C)C(C)(C)C)c2)cn1
Agent: CC(C)(C)[Si](C)(C)OCCn1ccc2cc(N)ccc21
Agent: CC(C)(C)c1ccc(/C=C/C(=O)O)cn1
Product: CC(C)(C)c1ccc(/C=C/C(=O)Nc2ccc3c(ccn3CCO)c2)cn1

Procedure:
(2E)-3-[6-(tert-butyl)(3-pyridyl)]-N-{1-[2-(1,1,2,2-tetramethyl-1-silapropoxy)ethyl]indol-5-yl}prop-2-enamide. Analogous to the procedure used to prepare Example 1, (2E)-3-[6-(tert-butyl)(3-pyridyl)]prop-2-enoic acid, Example 44(b), (41 mg, 0.20 inmol) and 1-[2-(1,1,2,2-tetramethyl-1-silapropoxy)ethyl]indole-5-ylamine, Example 73(a), (60 mg, 0.20 mmol) provided the title product. MS (ESI, pos. ion) m/z: 478 (M+1).
Reaction SMILES: [C:1]1(/[C:7](/[C:13]#[C:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[CH:8]\[C:9]([O:11]C)=[O:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CO.[OH-].[Na+]>O1CCCC1>[C:1]1(/[C:7](/[C:13]#[C:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[CH:8]\[C:9]([OH:11])=[O:10])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: COC(=O)/C=C(/C#Cc1ccccc1)c1ccccc1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: C1CCOC1
Product: O=C(O)/C=C(/C#Cc1ccccc1)c1ccccc1
Temperature: 25 °C
Reaction time: 18 h
Yield: 96.4 %

Procedure:
A mixture of 1.000 g of methyl (E)-3,5-diphenylpent-2-en-4-ynoate (prepared as described in Preparation 104), 15 ml of methanol, 7.5 ml of tetrahydrofuran and 15 ml of a 10% w/v aqueous solution of sodium hydroxide was stirred for 18 hours at room temperature. At the end of this time, the solvent was distilled off under reduced pressure. The resulting residue was diluted with water and extracted twice with diethyl ether. The ethereal extracts were washed with water, dried over anhydrous sodium sulfate and condensed by evaporation under reduced pressure, to give 0.912 g of the title compound, melting at 124°-126° C. (after recrystallisation from a mixture of methylene chloride and hexane).