Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([OH:21])[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][CH2:18][CH2:19][CH3:20].C(N(CC)CC)C.[Cl:29][C:30]1[CH:35]=[CH:34][C:33]([S:36](Cl)(=[O:38])=[O:37])=[CH:32][CH:31]=1>C(Cl)Cl>[CH2:1]([O:21][S:36]([C:33]1[CH:34]=[CH:35][C:30]([Cl:29])=[CH:31][CH:32]=1)(=[O:38])=[O:37])[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][CH2:18][CH2:19][CH3:20]
Reactant: O=S(=O)(Cl)c1ccc(Cl)cc1
Reactant: CCCCCCCCCCCCCCCCCCCCO
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CCCCCCCCCCCCCCCCCCCCOS(=O)(=O)c1ccc(Cl)cc1
Reaction time: 24 h

Procedure:
To a stirred solution of eicosanol (5.0 g, 16.70 mmol) and triethylamine (4 ml) in methylene chloride (80 ml) was added dropwise a solution of 4-chlorobenzene-sulphonyl chloride (3.90 g, 18.50 mmol) in methylene chloride (20 ml) and this solution was stirred for 24 h. The reaction mixture was then diluted with more methylene chloride (100 ml) and washed with water (2×75 ml). The organic layer was dried over MgSO4, filtered and concentrated to give a crude product which was recrystallized from methanol to give n-eicosanyl-4-chlorobenzenesulphonate the product (5.10 g, 65%) m.p. 69°-70° C. max; 3000-2800, 1367, 1184, 1176, 963 cm-1. m/z, 472 (M+). Found C, 66.16%; H 9.75%; S, 6.74% Cl, 7.40% C26H45O3SCl requires C, 66.00%; H, 9.59%; S, 6.78%; Cl, 7.49%. 1Hnmr, 0.855 (t, J-6.6 Hz, 3H); 1.10-1.65 (m); 4.030 (t, J=6.4 Hz, 2H); 7.48-7.53 (m, 2H); 7.80-7.84 (m, 2H).
Reaction SMILES: [N+:1]([C:4]1[CH:13]=[CH:12][C:11]([C:14]#[N:15])=[C:10]2[C:5]=1[CH:6]=[CH:7][CH:8]=[N:9]2)([O-])=O.CCO.[Cl-].[NH4+]>C1COCC1.[Fe]>[NH2:1][C:4]1[CH:13]=[CH:12][C:11]([C:14]#[N:15])=[C:10]2[C:5]=1[CH:6]=[CH:7][CH:8]=[N:9]2
Reactant: N#Cc1ccc([N+](=O)[O-])c2cccnc12
Agent: [Fe]
Agent: [Cl-]
Agent: [NH4+]
Solvent: CCO
Solvent: C1CCOC1
Product: N#Cc1ccc(N)c2cccnc12
Temperature: 70 °C
Reaction time: 1 h
Yield: 100 %

Procedure:
Compound 464B (6.00 g, 30.1 mmol) was dissolved in THF (150 mL) at reflux with mechanical stirring. EtOH (150 mL) was then added followed by aqueous ammonium chloride (2.4 g/225 mL water). The mixture was heated at 70° C. and then iron powder (325 mesh, 6.75 g, 120 mmol) was added with vigorous mechanical stirring. After 1 h, the reaction was cooled to 22° C. and filtered through Celite rinsing with methylene chloride. The filtrate was then concentrated to ˜250 mL and the pH was adjusted to 10 by addition of 1N NaOH. The solution was then extracted with ethyl acetate (5×150 mL). The combined organic layers were washed once with brine (250 mL) and then dried over anhydrous magnesium sulfate. Concentration in vacuo gave 5.09 g (100%) of compound 464C as a yellow solid. HPLC: 99% at 1.143 min (retention time) (YMC S5 ODS column, 4.6×50 mm, eluting with 10-90% aqueous methanol over 4 min containing 0.2% phosphoric acid, 4 mL/min, monitoring at 220 nm). MS (ES): m/z 170.16 [M+H]+.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:19]=[C:20]([O:24][CH3:25])[C:21]=1[O:22][CH3:23])[CH2:6][N:7]1[CH2:12][CH2:11][NH:10][CH2:9][CH:8]1[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[CH2:26]([N:28]([CH2:31][CH2:32]Cl)[CH2:29][CH3:30])[CH3:27]>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:19]=[C:20]([O:24][CH3:25])[C:21]=1[O:22][CH3:23])[CH2:6][N:7]1[CH2:12][CH2:11][N:10]([CH2:27][CH2:26][N:28]([CH2:31][CH3:32])[CH2:29][CH3:30])[CH2:9][CH:8]1[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: CCN(CC)CCCl
Reactant: COc1cc(CN2CCNCC2c2ccccc2)cc(OC)c1OC
Product: CCN(CC)CCN1CCN(Cc2cc(OC)c(OC)c(OC)c2)C(c2ccccc2)C1

Procedure:
1-(3',4',5'-Trimethoxy benzyl)-2-phenyl piperazine prepared according to Example 11, is alkylated by means of diethylamino ethylchloride by following the procedure described in Example 2 (c). The resulting reaction product is obtained in the form of yellow oil boiling at 200° C./0.03 mm. Hg.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[OH:9].C(=O)([O-])[O-].[K+].[K+].CN(C)C=O.[F:21][C:22]1[CH:27]=[C:26]([N+:28]([O-:30])=[O:29])[C:25](F)=[CH:24][C:23]=1[NH:32][C:33](=[O:35])[CH3:34]>O>[F:21][C:22]1[CH:27]=[C:26]([N+:28]([O-:30])=[O:29])[C:25]([O:9][C:4]2[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=2[O:2][CH3:1])=[CH:24][C:23]=1[NH:32][C:33](=[O:35])[CH3:34]
Reactant: COc1ccccc1O
Reactant: CC(=O)Nc1cc(F)c([N+](=O)[O-])cc1F
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: COc1ccccc1Oc1cc(NC(C)=O)c(F)cc1[N+](=O)[O-]
Temperature: 60 °C
Yield: 86.6 %

Procedure:
First, 2.73 g of 2-methoxyphenol and 5.5 g of potassium carbonate were added to 20 ml of N,N-dimethylformamide, and the temperature was increased to 60° C. To the mixture was added dropwise a solution consisting of 4.3 g of N-(2,5-difluoro-4-nitrophenyl)acetamide and 30 ml of N,N-dimethylformamide at a temperature of 60° C. to 65° C. After stirring while keeping the temperature for 1 hour, the mixture was cooled to room temperature and then poured into water, and the mixture was extracted with ethyl acetate. The organic layer was washed with diluted hydrochloric acid and water, dried over magnesium sulfate, and then concentrated to give 5.52 g of N-[2-fluoro-5-(2-methoxyphenoxy)-4-nitrophenyl]acetamide.
Reaction SMILES: [F:1][P-:2]([F:7])([F:6])([F:5])([F:4])[F:3].[C:8]1([CH3:27])[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[S+:14]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.[O-][O-].[Na+].[Na+].ClC(Cl)(Cl)C(Cl)=[O:35]>CO>[F:1][P-:2]([F:7])([F:6])([F:5])([F:4])[F:3].[C:8]1([CH3:27])[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[S+:14]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:35]
Reactant: O=C(Cl)C(Cl)(Cl)Cl
Reactant: Cc1ccccc1[S+](c1ccccc1)c1ccccc1
Agent: F[P-](F)(F)(F)(F)F
Agent: [Na+]
Agent: [O-][O-]
Solvent: CO
Product: Cc1ccccc1[S+](=O)(c1ccccc1)c1ccccc1
Yield: 0.1 %

Procedure:
(Tolyl)diphenylsulphonium hexafluorophosphate (1.08 g, 2.57 mol) is dissolved in methanol (40 ml) with cooling in an ice-water bath. Sodium peroxide (2.42 g, 31 mmol) is added slowly. After 15 mins a solution of trichloro- acetyl chloride (1.4 ml, 12.5 mol) in methanol (30 ml) is added over 20 mins. After a further 30 mins the reaction mixture is filtered under vacuum and the filtrate evaporated in vacuo. Water is added and the resulting solid collected, washed with water and ether to give (tolyl)diphenylsulphoxonium hexafluorophosphate (0.72 g, 64% ) with spectra identical to those of authentic material.
Reaction SMILES: [OH-].[K+].[C:3]([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[NH:10][CH:9]=[CH:8]2)#[N:4].O.Cl.[NH:16]1[CH2:21][CH2:20][C:19](=O)[CH2:18][CH2:17]1>CO>[C:3]([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[NH:10][CH:9]=[C:8]2[C:19]1[CH2:20][CH2:21][NH:16][CH2:17][CH:18]=1)#[N:4]
Reactant: O=C1CCNCC1
Reactant: N#Cc1ccc2[nH]ccc2c1
Agent: Cl
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: N#Cc1ccc2[nH]cc(C3=CCNCC3)c2c1
Temperature: 25 °C
Yield: 60 %

Procedure:
To a solution of 8.8 gm (157 mMol) potassium hydroxide in 85 mL methanol were added 8.15 gm (57.33 mMol) 5-cyano-1H-indole and 7.86 gm (51.17 mMol) 4-piperidone hydrochloride monohydrate. The resulting mixture was heated to reflux for 48 hours and was then allowed to cool to room temperature. The reaction mixture was concentrated under reduced pressure to about half volume and was then treated with 1M HCl until the pH of the solution was between 1 and 2. The resulting solution was extracted twice with 100 mL of diethyl ether and the remaining aqueous phase was treated with 5N sodium hydroxide until the pH of the solution was between 12 and 14. This aqueous phase was extracted 5 times with 10% methanol in dichloromethane. These organic phases were combined, dried over sodium sulfate and concentrated under reduced pressure to a residue. This residue was subjected to flash silica gel chromatography, eluting with dichloromethane which contained 20% methanol and 2% ammonium hydroxide. Fractions shown to contain product were combined and concentrated under reduced pressure to give 6.86 gm (60%) of the title compound as a solid.
Reaction SMILES: [F:1][C:2]1[C:3](=O)[NH:4][C:5](=[O:8])[NH:6][CH:7]=1.P12(SP3(SP(SP(S3)(S1)=S)(=S)S2)=S)=[S:11].O1CCOCC1>N1C=CC=CC=1>[F:1][C:2]1[C:3](=[S:11])[NH:4][C:5](=[O:8])[NH:6][CH:7]=1
Reactant: O=c1[nH]cc(F)c(=O)[nH]1
Reactant: S=P12SP3(=S)SP(=S)(S1)SP(=S)(S2)S3
Solvent: C1COCCO1
Solvent: c1ccncc1
Product: O=c1[nH]cc(F)c(=S)[nH]1
Yield: 80 %

Procedure:
Prepared from 5-fluorouracil by the method of Ueda and Fox (see above) using phosphorus pentasulphide in pyridine. We find that dioxan is a better solvent in this reaction in which case the yield was 80% of a more pure product.
Reaction SMILES: [F:1][C:2]([F:14])([F:13])[C:3]1[CH:4]=[C:5]([CH:10]=[CH:11][CH:12]=1)[C:6]([NH:8][NH2:9])=[O:7].[O:15]([C:22]1[C:27]([C:28](Cl)=[O:29])=[CH:26][CH:25]=[CH:24][N:23]=1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>N1C=CC=CC=1>[O:15]([C:22]1[C:27]([C:28]([NH:9][NH:8][C:6](=[O:7])[C:5]2[CH:10]=[CH:11][CH:12]=[C:3]([C:2]([F:13])([F:14])[F:1])[CH:4]=2)=[O:29])=[CH:26][CH:25]=[CH:24][N:23]=1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1
Reactant: NNC(=O)c1cccc(C(F)(F)F)c1
Reactant: O=C(Cl)c1cccnc1Oc1ccccc1
Solvent: c1ccncc1
Product: O=C(NNC(=O)c1cccnc1Oc1ccccc1)c1cccc(C(F)(F)F)c1
Yield: 53.3 %

Procedure:
A solution of 3-(trifluoromethyl)benzhydrazide (102.1 mg, 0.5 mmol), 2-phenoxypyridine-3-carbonyl chloride (117 mg, 0.5 mmol) in pyridine (5 mL) was refluxed for 2 h. It was evaporated in vacuo and the residue was purified by column chromatography (silica gel, EtOAc/CH2Cl2=4:1) to give 107 mg (54%) of the title compound. 1H NMR (CDCl3): 10.88 (d, J=6.3 Hz, 1H), 9.80 (d, J=6.3 Hz, 1H), 8.60 (m, 1H), 8.30 (m, 1H), 8.17 (s, 1H), 8.06 (d, J=8.1 Hz, 1H), 7.81 (d, J=7.8 Hz, 1H), 7.61 (t, J=7.2 Hz, 1H), 7.51–7.46 (m, 2H), 7.34–7.17 (m, 4H).
Reaction SMILES: COC1C=CC=CC=1C[NH:10][C@H:11]1[CH:16]2[CH2:17][CH2:18][N:13]([CH2:14][CH2:15]2)[C@H:12]1[CH:19]([C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.Cl.[H][H]>CO.[OH-].[OH-].[Pd+2]>[C:26]1([CH:19]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C@H:12]2[C@@H:11]([NH2:10])[CH:16]3[CH2:17][CH2:18][N:13]2[CH2:14][CH2:15]3)[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1
Reactant: [H][H]
Reactant: COc1ccccc1CN[C@H]1C2CCN(CC2)[C@H]1C(c1ccccc1)c1ccccc1
Agent: [Pd+2]
Agent: Cl
Agent: [OH-]
Solvent: CO
Product: N[C@H]1C2CCN(CC2)[C@H]1C(c1ccccc1)c1ccccc1
Yield: 95.8 %

Procedure:
(2S,3S)-N-(2-methoxyphenyl)methyl-2-diphenylmethyl-1-azabicyclo[2.2.2]octan-3-amine (4.13 g, 10 mmol) was hydrogenated in methanol (MeOH) (40 ml)/6N HCl (10 ml) by using 20% palladium hydroxide on carbon (0.2 g) at 2.5 kg/cm2 of hydrogen for 60 hours. The filtrate was concentrated and the residue was partitioned between 2N NaOH and CH2Cl2. The organic layer was dried over MgSO4, and concentrated to give the crude product, which was recrystallized from ethanol (EtOH) to afford the pure title compound (2.80 g, 96%).
Reaction SMILES: [C:1]1([CH2:7][C:8]([OH:10])=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH:11](=O)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C(OC(=O)C)(=O)C>>[C:1]1([C:7](=[CH:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[C:8]([OH:10])=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: O=C(O)Cc1ccccc1
Reactant: O=Cc1ccccc1
Solvent: CC(=O)OC(C)=O
Product: O=C(O)C(=Cc1ccccc1)c1ccccc1

Procedure:
Phenyl acetic acid (1.94 g, 14.24 mmol) and benzaldehyde (1.491 g, 14.05 mmol), TEA (5 ml) and acetic anhydride (5 ml) were reacted to give 2,3-diphenyl-acrylic acid as similar procedure.
Reaction SMILES: [NH2:1][C@H:2]([P:11](=[O:18])([O:15][CH2:16][CH3:17])[O:12][CH2:13][CH3:14])[CH2:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.C(N(CC)CC)C.FC(F)(F)S(O[C@H:32]([CH2:43][CH:44]([CH3:46])[CH3:45])[C:33]([O:35][CH2:36][C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)=[O:34])(=O)=O>ClCCl>[CH2:36]([O:35][C:33](=[O:34])[C@H:32]([CH2:43][CH:44]([CH3:45])[CH3:46])[NH:1][C@H:2]([P:11]([O:12][CH2:13][CH3:14])([O:15][CH2:16][CH3:17])=[O:18])[CH2:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1
Reactant: CCOP(=O)(OCC)[C@@H](N)CCc1ccccc1
Reactant: CC(C)C[C@@H](OS(=O)(=O)C(F)(F)F)C(=O)OCc1ccccc1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CCOP(=O)(OCC)[C@H](CCc1ccccc1)N[C@@H](CC(C)C)C(=O)OCc1ccccc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 33.9 %

Procedure:
To a solution of 400 mg of diethyl 1-(R)-amino-3-phenylpropylphosphonate in 5 ml of anhydrous dichloromethane was added a solution of 0.25 ml of triethylamine and 627 mg of benzyl 2-(R)-trifluoromethanesulfonyloxy-4-methylpentanoate in 2.5 ml of anhydrous dichloromethane, and the mixture was stirred at room temperature overnight. The reaction mixture was diluted with 30 ml of dichloromethane, and the diluted solution was washed with 20 ml of water and dried over anhydrous magnesium sulfate. Then the solvent was distilled off under reduced pressure. The residue was purified by silica gel chromatography (hexane: ethyl acetate=1:1) to yield the title compound as a colorless oil (238 mg).
Reaction SMILES: [C:1]([O:5][C:6](=[O:39])[NH:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[C:19]([C:33]4[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=4)=[CH:20][C:21]4[N:26]([CH2:27]CC#N)[C:25](=[O:31])[CH2:24][O:23][C:22]=4[N:32]=3)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].O=C1COC2N=[C:48](C3C=CC(C4(NC(=O)OC(C)(C)C)CCC4)=CC=3)[C:49](C3C=CC=CC=3)=[CH:50][C:43]=2[NH:42]1.BrCCCCC#N>>[C:1]([O:5][C:6](=[O:39])[NH:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[C:19]([C:33]4[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=4)=[CH:20][C:21]4[N:26]([CH2:27][CH2:48][CH2:49][CH2:50][C:43]#[N:42])[C:25](=[O:31])[CH2:24][O:23][C:22]=4[N:32]=3)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)OC(=O)NC1(c2ccc(-c3nc4c(cc3-c3ccccc3)NC(=O)CO4)cc2)CCC1
Reactant: CC(C)(C)OC(=O)NC1(c2ccc(-c3nc4c(cc3-c3ccccc3)N(CCC#N)C(=O)CO4)cc2)CCC1
Agent: N#CCCCCBr
Product: CC(C)(C)OC(=O)NC1(c2ccc(-c3nc4c(cc3-c3ccccc3)N(CCCCC#N)C(=O)CO4)cc2)CCC1

Procedure:
Following the procedure for tert-butyl(1-(4-(1-(2-cyanoethyl)-2-oxo-7-phenyl-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-6-yl)phenyl)cyclobutyl)carbamate, tert-butyl 1-(4-(2-oxo-7-phenyl-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-6-yl)phenyl)cyclobutylcarbamate (100 mg, 0.212 mmol) was reacted with 5-bromopentanenitrile (103 mg, 0.636 mmol) to afford the title compound (82 mg. 1H NMR (500 MHz, CDCl3): 7.20-7.33 (10H, m), 5.03 (1H, br), 4.91 (2H, s), 4.05 (2H, t), 2.45-2.51 (6H, m), 2.05-2.10 (1H, m), 1.88-1.94 (2H, m), 1.67-1.85 (3H, m), 1.27-1.38 (9H, br).
Reaction SMILES: [F:1][CH2:2][CH2:3][N:4]1[C:16]2[CH2:15][CH2:14][CH2:13][CH:12]([C:17](Cl)=[O:18])[C:11]=2[C:10]2[C:5]1=[CH:6][CH:7]=[CH:8][C:9]=2[O:20][CH3:21].[CH2:22]([NH:24][CH2:25][CH3:26])[CH3:23]>ClCCl>[CH2:22]([N:24]([CH2:25][CH3:26])[C:17]([CH:12]1[C:11]2[C:10]3[C:5](=[CH:6][CH:7]=[CH:8][C:9]=3[O:20][CH3:21])[N:4]([CH2:3][CH2:2][F:1])[C:16]=2[CH2:15][CH2:14][CH2:13]1)=[O:18])[CH3:23]
Reactant: CCNCC
Reactant: COc1cccc2c1c1c(n2CCF)CCCC1C(=O)Cl
Solvent: ClCCl
Product: CCN(CC)C(=O)C1CCCc2c1c1c(OC)cccc1n2CCF
Temperature: 25 °C
Reaction time: 8 h
Yield: 57.7 %

Procedure:
9-(2-fluoroethyl)-5-methoxy-2,3,4,9-tetrahydro-1H-carbazole-4-carbonyl chloride (18) (371 mg, 1.2 mmol) was dissolved in dichloromethane (2 mL) and cooled to 0° C. diethylamine (177 mg, 2.4 mmol, 250 μL) was then added and the reaction was stirred overnight at RT. The reaction was quenched with 10% aqueous potassium carbonate (2 mL). The dichloromethane layer was collected through a phase separator then concentrated in vacuo. The crude material was purified by silica gel chromatography eluting with petrol (A): ethyl acetate (B) (50-100% (B), 50 g, 35.2 CV, 40 mL/min) to afford a pale yellow solid. The solid was next triturated with a minimum amount of diethyl ether to afford 240 mg (58%) of 9-(2-Fluoroethyl)-5-methoxy-2,3,4,9-tetrahydro-1H-carbazole-4-carboxylic acid diethyl amide. The structure was confirmed by 13C NMR (75 MHz, CDCl3): δC 13.0, 14.6, 19.9, 21.9, 28.0, 36.3, 40.5, 41.9, 43.1 (d, JCF=23 Hz), 54.7, 82.0 (d, JCF=173 Hz), 99.7, 102.1, 108.3, 117.0, 121.5, 135.3, 137.4, 153.3, and 174.8.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[C:6]([CH2:8][C:9]([OH:11])=[O:10])[CH:5]=[CH:4][N:3]=1.S(=O)(=O)(O)O.C([O-])(O)=O.[Na+].[C:22](OCC)(=O)[CH3:23]>C(O)C>[CH2:22]([O:10][C:9](=[O:11])[CH2:8][C:6]1[CH:5]=[CH:4][N:3]=[C:2]([Br:1])[CH:7]=1)[CH3:23]
Reactant: CCOC(C)=O
Reactant: O=C(O)Cc1ccnc(Br)c1
Agent: O=C([O-])O
Agent: O=S(=O)(O)O
Agent: [Na+]
Solvent: CCO
Product: CCOC(=O)Cc1ccnc(Br)c1
Temperature: 90 °C

Procedure:
To a solution of (2-bromo-pyridin-4-yl)-acetic acid (60.0 g, 277.7 mmol) in ethanol (600 ml), conc: sulfuric acid (5.0 ml) was added at rt and the reaction mixture was heated at 90° C. for 9 h. Reaction mixture was cooled to rt and concentrated under reduced pressure to remove solvent completely. The residue obtained was cooled to 0° C. and pH was adjusted to 8 using 10% aqueous NaHCO3 solution. The resultant contents were worked up with ethyl acetate by washing with water, brine and dried over anhy. Na2SO4. Organic layer was concentrated under reduced pressure to obtain crude compound. Column chromatography purification of the crude compound using 15% ethyl acetate in hexane as eluent furnished title compound as a brown oil. Yield: 65.0 g (88.5%). TLC (30% ethyl acetate in hexane) Rf=0.39; LCMS: RtH7=0.824 [M+1]+=243.8 and 245.8; HPLC RtH9=3.759 min (69%); 1H NMR (300 MHz, CDCl3): δ 8.32 (t, 1H), 7.43 (s, 1H), 7.21-7.15 (M, 1H), 4.18 (q, 2H), 1.27 (t, 3H).
Reaction SMILES: Cl.[CH3:2][C:3]1[N:4]=[N:5][N:6]([CH2:8][C:9]([OH:11])=O)[CH:7]=1.[NH2:12][C@@H:13]([CH2:31][O:32][CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)[C:14]([NH:16][C:17]1[CH:22]=[CH:21][C:20]([O:23][C:24]2[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=2)=[CH:19][CH:18]=1)=[O:15]>>[CH2:33]([O:32][CH2:31][C@H:13]([NH:12][C:9](=[O:11])[CH2:8][N:6]1[CH:7]=[C:3]([CH3:2])[N:4]=[N:5]1)[C:14]([NH:16][C:17]1[CH:22]=[CH:21][C:20]([O:23][C:24]2[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=2)=[CH:19][CH:18]=1)=[O:15])[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1
Reactant: Cc1cn(CC(=O)O)nn1
Reactant: N[C@@H](COCc1ccccc1)C(=O)Nc1ccc(Oc2ccc(F)cc2)cc1
Agent: Cl
Product: Cc1cn(CC(=O)N[C@@H](COCc2ccccc2)C(=O)Nc2ccc(Oc3ccc(F)cc3)cc2)nn1
Yield: 18 %

Procedure:
Proceeding as in Example 1, but substituting 2-(4-methyl-1,2,3-triazol-1-yl)acetic acid hydrochloride and (S)-2-amino-3-(benzyloxy)-N-(4-(4-fluorophenoxy)phenyl)propanamide, gave Compound 153, (S)-3-(benzyloxy)-N-(4-(4-fluorophenoxy)phenyl)-2-(2-(4-methyl-1H-1,2,3-triazol-1-yl)acetamido)propanamide (13 mg, 18%); Major isomer: 1H-NMR (400 MHz, DMSO-D6): σ 10.24 (br s, 1H), 8.84-8.82 (d, 1H), 7.76 (s, 2H), 7.63-7.59 (d, 2H), 7.32-7.27 (m, 5H), 7.23-7.19 (t, 2H), 7.04-6.98 (m, 4H), 5.15 (s, 1H), 4.75-4.70 (m, 1H), 4.54 (s, 2H), 3.70-3.68 (d, 2H), 2.23 (s, 3H). MS (EI) for C27H26FN5O4. found 504.0 (MH+).
Reaction SMILES: [CH3:1][O:2][C:3]([CH:5]1[CH2:9][CH2:8][CH2:7][CH:6]1[C:10]([OH:12])=O)=[O:4].Cl.[NH2:14][CH2:15][C:16]#[N:17].F[P-](F)(F)(F)(F)F.N1([PH+](N2CCCC2)N2CCCC2)CCCC1.C(N(CC)CC)C>CN(C)C=O>[C:15]([CH2:16][NH:17][C:10]([C@@H:6]1[CH2:7][CH2:8][CH2:9][C@H:5]1[C:3]([O:2][CH3:1])=[O:4])=[O:12])#[N:14]
Reactant: N#CCN
Reactant: COC(=O)C1CCCC1C(=O)O
Agent: C1CCN([PH+](N2CCCC2)N2CCCC2)C1
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: COC(=O)[C@@H]1CCC[C@H]1C(=O)NCC#N
Temperature: 0 °C
Reaction time: 3 h

Procedure:
Cyclopentane-1,2-dicarboxylic acid monomethyl ester (2.21 g, 12.8 mmol), 2-aminoacetonitrile hydrochloride (1.48 g, 16.0 mmol) and benzotriazol-1-yloxy)tripyrrolidinophosphonium hexafluorophosphate (PyBOP) (7.34 g, 14.1 mmol) were dissolved in dimethylformamide (26 mL) and the reaction mixture was cooled to 0° C. Triethylamine (4.9 mL, 35 mmol) was added and the reaction mixture was stirred at ambient temperature for 3 h. The reaction mixture was partitioned between water (150 mL) and ethyl acetate (100 mL). The product was extracted into ethyl acetate, washed with saturated sodium chloride aqueous solution, dried over anhydrous sodium sulfate and concentrated. The residue was chromatographed on silica gel with 3:2 ethyl acetate:hexanes eluent to give methyl trans-2-{[(cyanomethyl)amino]carbonyl}cyclopentanecarboxylate as a colorless solid.
Reaction SMILES: C[Si](C)(C)[C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:14]=[CH:13][C:12](I)=[CH:11][C:10]=2F)=[C:5](F)[C:4]=1F.C([C:24]1[CH:29]=[CH:28][C:27](B(O)O)=[CH:26][CH:25]=1)CC.OCC(C)(CO)C.CC(C)=O>CC(O)C.CC([O-])=O.CC([O-])=O.[Pd+2]>[C:6]1([C:9]2[C:10]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH:7]=[CH:8][CH:3]=[CH:4][CH:5]=1
Reactant: CCCc1ccc(B(O)O)cc1
Reactant: C[Si](C)(C)c1ccc(-c2ccc(I)cc2F)c(F)c1F
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: CC(C)(CO)CO
Solvent: CC(C)=O
Solvent: CC(C)O
Product: c1ccc(-c2ccccc2-c2ccccc2)cc1
Yield: 89 %

Procedure:
A solution of (2 mmol) of 8, (22 mmol) of 4-propylphenylboronic acid, 250 mg (2.40 mmol) of neopentyl glycol, 1.53 g (4.84 mmol) of Ba(OH)2. 8H2O, 1.35 ml (0.103 mmol, 5 mol %) of a 76 mM acetone solution of Pd(OAc)2 in 20 ml of 95% i-PrOH is stirred at 80° C. for 12 hours. The solvent is subsequently removed under reduced pressure. 5 ml of 2 M HCl are added to the residue, and the mixture is extracted with dichloromethane (3×5 ml). The combined organic phases are dried over MgSO4 and filtered through SiO2. The solvent is removed under reduced pressure, and the residue is converted into 10 (yield: 89%).
Reaction SMILES: Cl[CH2:2][C:3]1[N:4]([C:20]2[CH:25]=[CH:24][C:23]([N+:26]([O-:28])=[O:27])=[CH:22][CH:21]=2)[CH:5]=[C:6]([C:8]2[C:9]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)=[N:10][O:11][C:12]=2[CH3:13])[N:7]=1.[O-:29][CH2:30][CH3:31].[Na+]>C(O)C.CO>[CH2:30]([O:29][CH2:2][C:3]1[N:4]([C:20]2[CH:25]=[CH:24][C:23]([N+:26]([O-:28])=[O:27])=[CH:22][CH:21]=2)[CH:5]=[C:6]([C:8]2[C:9]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)=[N:10][O:11][C:12]=2[CH3:13])[N:7]=1)[CH3:31]
Reactant: CC[O-]
Reactant: Cc1onc(-c2ccccc2)c1-c1cn(-c2ccc([N+](=O)[O-])cc2)c(CCl)n1
Agent: [Na+]
Solvent: CO
Solvent: CCO
Product: CCOCc1nc(-c2c(-c3ccccc3)noc2C)cn1-c1ccc([N+](=O)[O-])cc1
Yield: 92 %

Procedure:
As described for Example 150, 4-[2-chloromethyl-1-(4-nitro-phenyl)-1H-imidazol-4-yl]-5-methyl-3-phenyl-isoxazole (50 mg, 0.13 mmol), using sodium ethoxide in ethanol instead of sodium methoxide in methanol, was converted to the title compound (47 mg, 92%) which was obtained as a yellow solid. MS: m/e=405.5 [M+H]+.
Reaction SMILES: [CH3:1][C:2]([CH3:9])([CH3:8])[C@@H:3]([OH:7])[CH2:4][C:5]#[CH:6].C(N(CC)CC)C.FC(F)(F)S(O[Si:23]([CH2:28][CH3:29])([CH2:26][CH3:27])[CH2:24][CH3:25])(=O)=O.C(=O)(O)[O-].[Na+]>ClCCl>[CH3:1][C:2]([CH3:9])([CH3:8])[C@@H:3]([O:7][Si:23]([CH2:28][CH3:29])([CH2:26][CH3:27])[CH2:24][CH3:25])[CH2:4][C:5]#[CH:6]
Reactant: CC[Si](CC)(CC)OS(=O)(=O)C(F)(F)F
Reactant: C#CC[C@H](O)C(C)(C)C
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: C#CC[C@H](O[Si](CC)(CC)CC)C(C)(C)C
Temperature: 0 °C
Reaction time: 0.67 h
Yield: 92.3 %

Procedure:
A mixture of (S)-5,5-dimethyl-1-hexyn-4-ol (1.96 g 16 mmol), triethylamine (4.5 ml, 32 mmol) and dry dichloromethane (30 ml) was cooled to 0° C. under a nitrogen atmosphere. Triethylsilyl trifluoromethanesulphonate (5.4 ml, 24 mmol) was slowly added and the mixture stirred at 0° C. for a further 40 min. The mixture was treated with saturated sodium bicarbonate solution (60 ml) and the organic layer separated. The aqueous layer was extracted with dichloromethane (3×20 ml) and the combined dichloromethane extracts dried (MgSO4) and evaporated. The residue was purified by column chromatorgaphy (silica eluted with Petroleum ether 40-60°) to yield the title compound 3.55 g (95%).