Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3](=[O:39])[CH2:4][CH2:5][C:6]([NH:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]([N:17]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[C@H:20]([N:27]([C:35](=[O:37])[CH3:36])[C:28]3[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][CH:29]=3)[CH2:19][C@@H:18]2[CH3:38])=[O:16])=[CH:11][CH:10]=1)=[O:7].[H-].[Na+].I[CH3:43]>CN(C=O)C>[CH3:1][O:2][C:3](=[O:39])[CH2:4][CH2:5][C:6]([N:8]([C:9]1[CH:10]=[CH:11][C:12]([C:15]([N:17]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[C@H:20]([N:27]([C:35](=[O:37])[CH3:36])[C:28]3[CH:29]=[CH:30][C:31]([Cl:34])=[CH:32][CH:33]=3)[CH2:19][C@@H:18]2[CH3:38])=[O:16])=[CH:13][CH:14]=1)[CH3:43])=[O:7]
Reactant: CI
Reactant: COC(=O)CCC(=O)Nc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COC(=O)CCC(=O)N(C)c1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 28.5 %

Procedure:
To a solution of (2S,4R)-N-(4-{4-[Acetyl-(4-chloro-phenyl)-amino]-2-methyl-3,4-dihydro-2H-quinoline-1-carbonyl}-phenyl)-succinamic acid methyl ester (55 mg, 0.100 mmoles) in DMF was added sodium hydride (60% dispersion in oil). After 30 minutes, iodomethane (16 uL, 0.11 mmoles) was added to the reaction mixture and stirred at room temperature overnight. Reaction was quenched with water and extracted with ethyl acetate. Combined organics were washed with saturated aqueous sodium bicarbonate, brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. Product was purified on silica gel by flash chromatography using 100% ethyl acetate and 90% ethyl acetate/10% methanol to afford (2S,4R)-N-(4-{4-[Acetyl-(4-chloro-phenyl)-amino]-2-methyl-3,4-dihydro-2H-quinoline-1-carbonyl}-phenyl)-N-methyl-succinamic acid methyl ester (16 mg, 26%).
Reaction SMILES: C1C([N+]([O-])=[O:8])=CC=C(O)C=1.[CH:11]1([N:17]=[C:18]=[N:19][CH:20]2[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]2)[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1>C(OCC)(=O)C>[C:18]([NH:17][CH:11]1[CH2:12][CH2:13][CH2:14][CH2:15][CH2:16]1)([NH:19][CH:20]1[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]1)=[O:8]
Reactant: O=[N+]([O-])c1ccc(O)cc1
Reactant: C(=NC1CCCCC1)=NC1CCCCC1
Solvent: CCOC(C)=O
Product: O=C(NC1CCCCC1)NC1CCCCC1
Temperature: -5 °C
Reaction time: 2 h

Procedure:
The above product (0.75 g, 0.0024 mole) is dissolved in 50 ml ethyl acetate. This is cooled to -5° C. and p-nitrophenol is added followed by the portionwise addition of dicyclohexylcarbodiimide. The reaction mixture is stirred at -5° C. for 2 hours. The formed dicyclohexylurea is filtered off. After concentrating to a 10 ml volume, the reaction mixture is cooled overnight. More dicyclohexylurea is formed. This is filtered and the filtrate is concentrated in vacuo to yield 0.95 g of active ester, (the p-nitrophenyl ester of N-[N-[2-(mercaptomethyl)-4-methyl-1-oxopentyl]glycyl]glycine).
Reaction SMILES: [CH3:1][CH:2]([CH3:14])[CH:3]([NH:6][C:7](=[O:13])[O:8][C:9]([CH3:12])([CH3:11])[CH3:10])[CH:4]=O.[N+](=[C:17](P(=O)(OC)OC)C(=O)C)=[N-].C(=O)([O-])[O-].[K+].[K+]>CO>[CH3:1][CH:2]([CH3:14])[CH:3]([NH:6][C:7](=[O:13])[O:8][C:9]([CH3:12])([CH3:11])[CH3:10])[C:4]#[CH:17]
Reactant: CC(C)C(C=O)NC(=O)OC(C)(C)C
Reactant: COP(=O)(OC)C(=[N+]=[N-])C(C)=O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Product: C#CC(NC(=O)OC(C)(C)C)C(C)C
Temperature: 25 °C
Reaction time: 16 h
Yield: 82.4 %

Procedure:
To a solution of 1.25 g of tert-butyl 3-methyl-1-oxobutan-2-ylcarbamate (Formula 21) and 1.79 g of dimethyl 1-diazo-2-oxopropylphosphonate (Formula 15) in 80 mL of methanol at 0° C. was added 1.72 g of potassium carbonate. The mixture was stirred at room temperature for 16 hours then quenched with saturated ammonium chloride solution and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate and concentrated. Column chromatography (15% ethyl acetate/hexane) gave 1.01 g of tert-butyl 4-methylpent-1-yn-3-ylcarbamate (Formula 22) as a clear oil. 1H NMR (300 MHz, CDCl3) δ 0.98-1.00 (m, 6H), 1.45 (s, 9H), 1.87-1.93 (m, 1H), 2.24-2.25 (m, 1H), 4.32 (br, 1H).
Reaction SMILES: C(Cl)(=O)C(Cl)=O.CS(C)=O.[CH2:11]([O:18][C@@H:19]([CH3:41])[C@H:20]([CH2:39]O)[NH:21][C:22]([O:24][CH2:25][CH:26]1[C:38]2[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=2)[C:32]2[C:27]1=[CH:28][CH:29]=[CH:30][CH:31]=2)=[O:23])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.CCN(C(C)C)C(C)C.C1(P(=[CH:70][C:71]([O:73][CH2:74][C:75]2[CH:80]=[CH:79][CH:78]=[CH:77][CH:76]=2)=[O:72])(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(Cl)Cl>[CH2:11]([O:18][C@@H:19]([CH3:41])[C@@H:20]([NH:21][C:22]([O:24][CH2:25][CH:26]1[C:38]2[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=2[C:32]2[C:27]1=[CH:28][CH:29]=[CH:30][CH:31]=2)=[O:23])/[CH:39]=[CH:70]/[C:71]([O:73][CH2:74][C:75]1[CH:80]=[CH:79][CH:78]=[CH:77][CH:76]=1)=[O:72])[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1
Reactant: C[C@H](OCc1ccccc1)[C@H](CO)NC(=O)OCC1c2ccccc2-c2ccccc21
Reactant: O=C(C=P(c1ccccc1)(c1ccccc1)c1ccccc1)OCc1ccccc1
Agent: O=C(Cl)C(=O)Cl
Solvent: CS(C)=O
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: C[C@H](OCc1ccccc1)[C@H](/C=C/C(=O)OCc1ccccc1)NC(=O)OCC1c2ccccc2-c2ccccc21
Temperature: -78 °C
Reaction time: 0.33 h

Procedure:
(From Mandal et al, J. Med. Chem. 2009, 52, 6126-41) To a solution of oxalyl chloride (8.0 mmol) in 30 mL of dry CH2Cl2, stirred at −78° C. under argon was added DMSO (16.0 mmol) via syringe dropwise with vigorous stirring. After 20 min, a solution of Fmoc-D-threoninol benzyl ether (5.0 mmol) in 20 mL of dry CH2Cl2, was added while maintaining the bath temperature at −78° C. Stirring was continued further for 30 min. Dry and distilled DIEA (30 mmol) was then added using a syringe and the reaction mixture then allowed to warm to room temperature without removing bath. The reaction mixture then quenched with 20 mL of ice-cold water and extracted with CH2Cl2 (3×80 mL). The combined organic layers were washed with 1N HCl (3×30 mL), brine (1×30 mL) and dried (MgSO4) and concentrated under vacuum. The crude aldehyde was used immediately for the next step without characterization. A mixture of the Fmoc-amino aldehyde (4.0 mmol) and benzyl (triphenylphosphoranylidene)-acetate (4.4 mmol) in dry CH2Cl2 (20 mL) was stirred for 3 h. The progress of the reaction was monitored by thin layer chromatography. After completion the solvent was removed in vacuo and the residue was purified by silica gel chromatography using EtOAc in hexane. Yield: 1.55 g (68%), white powder. 1H NMR (CDCl3, 300 MHz) δ 1.22 (d, J=5.7 Hz, 3H), 3.7 (m, 1H), 4.2 (t, J=6.6 Hz, 1H), 4.3-4.45 (m, 4H), 4.58 (d, J=11.7 Hz, 1H), 5.2 (s, 2H), 5.98 (d, J=15.3 Hz, 1H), 6.98 (m, 1H), 7.28-7.38 (m, 14H), 7.58 (d, J=7.5 Hz, 2H), 7.74 (d, J=7.5 Hz, 2H). 13C NMR (CDCl3, 75 MHz) δ 16.5, 47.3, 66.3, 66.9, 71.1, 75.1, 120.0, 121.7, 125.0, 127.0, 127.7, 127.8, 127.9, 128.3, 128.5, 128.6, 135.9, 137.7, 141.3, 143.8, 143.9, 147.2, 165.8. Anal (C35H33NO5) C, H, N: Calc'd: C, 76.76; H, 6.07; N, 2.56. Found: C, 76.61; H, 6.06; N, 2.55. HRMS (M+H) Calc'd: 548.2437. Found: 548.2451.
Reaction SMILES: [NH:1]1[C:5]2=[N:6][CH:7]=[CH:8][CH:9]=[C:4]2[C:3]([C:10]([O:12][CH3:13])=[O:11])=[CH:2]1.Cl[C:15]1[C:16]2[CH:23]=[CH:22][N:21]([CH3:24])[C:17]=2[N:18]=[CH:19][N:20]=1.C(=O)([O-])[O-].[K+].[K+].O>CS(C)=O.C(OCC)(=O)C>[CH3:24][N:21]1[C:17]2[N:18]=[CH:19][N:20]=[C:15]([N:1]3[C:5]4=[N:6][CH:7]=[CH:8][CH:9]=[C:4]4[C:3]([C:10]([O:12][CH3:13])=[O:11])=[CH:2]3)[C:16]=2[CH:23]=[CH:22]1
Reactant: Cn1ccc2c(Cl)ncnc21
Reactant: COC(=O)c1c[nH]c2ncccc12
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: CS(C)=O
Solvent: O
Product: COC(=O)c1cn(-c2ncnc3c2ccn3C)c2ncccc12
Temperature: 120 °C
Yield: 44.2 %

Procedure:
To 1.9 g (9.2 mmol) of methyl 1H-pyrrolo[2,3-b]pyridine-3-carboxylate in 50 cm3 of dimethylsulfoxyde under argon atmosphere, were added 1.85 g (11.0 mmol) of 4-chloro-7-methyl-7H-pyrrolo[2,3-d]pyrimidine, followed by 3.2 g (23.0 mmol) of potassium carbonate. The reaction mixture was heated at about 120° C. for 24 hours, upon which it was cooled to about 20° C. and treated with 200 cm3 of distilled water. The mixture was then treated with 300 cm3 and 150 cm3 of ethyl acetate and filtered on Celite®. The aqueous phase was extracted with 150 cm3 of ethyl acetate. The combined organic extracts were dried on magnesium sulfate and concentrated to dryness in vacuo (2.7 kPa). The residue was purified via column chromatography on silica gel (0,04–0,06 mm), with dichloromethane/methanol 99:1 v/v as eluting solvent. Thus, 1.25 g of methyl 1-(7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrrolo[2,3-b]pyridine-3-carboxylate were obtained as a light-yellow crystalline powder. mp: 207° C.
Reaction SMILES: [OH:1][CH:2]([CH2:39][CH2:40][CH2:41]O)[CH2:3][O:4][C@H:5]1[CH2:10][CH2:9][C@H:8]([N:11]2[C:16](=[O:17])[C:15]([CH2:18][C:19]3[CH:24]=[CH:23][C:22]([C:25]4[C:26]([C:31]#[N:32])=[CH:27][CH:28]=[CH:29][CH:30]=4)=[CH:21][CH:20]=3)=[C:14]([CH2:33][CH2:34][CH3:35])[N:13]3[N:36]=[CH:37][N:38]=[C:12]23)[CH2:7][CH2:6]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O.O>O1CCCC1>[O:17]=[C:16]1[C:15]([CH2:18][C:19]2[CH:20]=[CH:21][C:22]([C:25]3[C:26]([C:31]#[N:32])=[CH:27][CH:28]=[CH:29][CH:30]=3)=[CH:23][CH:24]=2)=[C:14]([CH2:33][CH2:34][CH3:35])[N:13]2[N:36]=[CH:37][N:38]=[C:12]2[N:11]1[C@H:8]1[CH2:9][CH2:10][C@H:5]([O:4][CH2:3][CH:2]2[CH2:39][CH2:40][CH2:41][O:1]2)[CH2:6][CH2:7]1
Reactant: CCCc1c(Cc2ccc(-c3ccccc3C#N)cc2)c(=O)n([C@H]2CC[C@H](OCC(O)CCCO)CC2)c2ncnn12
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: O
Solvent: C1CCOC1
Product: CCCc1c(Cc2ccc(-c3ccccc3C#N)cc2)c(=O)n([C@H]2CC[C@H](OCC3CCCO3)CC2)c2ncnn12
Temperature: 25 °C
Reaction time: 18 h

Procedure:
4′-[(4-{trans-4-[(2,5-Dihydroxypentyl)oxy]cyclohexyl}-5-oxo-7-propyl-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)methyl]biphenyl-2-carbonitrile (0.17 g) was dissolved in tetrahydrofuran (3 mL), triphenylphosphine (0.24 g) and then diethyl azodicarboxylate (0.40 g, 40% toluene solution) were added, and the mixture was stirred at room temperature for 18 hr. The reaction mixture was added to water, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography to give the title compound as a colorless solid (0.12 g, 74%).
Reaction SMILES: P(Br)(Br)Br.[Br:5][C:6]1[C:11]([O:12][CH3:13])=[CH:10][CH:9]=[C:8]([CH2:14][CH3:15])[N+:7]=1[O-].[OH-].[Na+]>C(Cl)Cl>[Br:5][C:6]1[C:11]([O:12][CH3:13])=[CH:10][CH:9]=[C:8]([CH2:14][CH3:15])[N:7]=1
Reactant: CCc1ccc(OC)c(Br)[n+]1[O-]
Agent: BrP(Br)Br
Agent: [Na+]
Agent: [OH-]
Solvent: ClCCl
Product: CCc1ccc(OC)c(Br)n1
Temperature: 50 °C

Procedure:
Phosphorous tribromide (1.3 mL) was added to a solution of 2-bromo-6-ethyl-3-methoxy-pyridine 1-oxide (0.3 g, 1.3 mmol, from step 4 of example A(2)) dissolved in CH2Cl2 (10 mL). The reaction mixture was heated to 50° C. for 1 hour. After cooling to room temperature the mixture was poured into ice and made basic with 15% NaOH and extracted with CH2Cl2. The organic extracts were dried over Na2SO4 and concentrated to a clear oil (0.28 g, 99%). 1H NMR (400 MHz, CDCl3): δ 1.27 (t, J=7.6 Hz, 3H), 2.76 (d, J=7.6 Hz, 2H), 3.89 (s, 3H), 7.06 (d, J=8.1 Hz, 1H), 7.09 (d, J=8.1 Hz, 1H).
Reaction SMILES: [N+:1]([C:4]1[CH:16]=[CH:15][C:7]([CH2:8][C:9]2[CH:14]=[CH:13][N:12]=[CH:11][CH:10]=2)=[CH:6][CH:5]=1)([O-])=O>CCO.[Pd]>[N:12]1[CH:13]=[CH:14][C:9]([CH2:8][C:7]2[CH:6]=[CH:5][C:4]([NH2:1])=[CH:16][CH:15]=2)=[CH:10][CH:11]=1
Reactant: O=[N+]([O-])c1ccc(Cc2ccncc2)cc1
Agent: [Pd]
Solvent: CCO
Product: Nc1ccc(Cc2ccncc2)cc1
Reaction time: 1 h
Yield: 89.7 %

Procedure:
To a solution of 4-(4-nitrobenzyl)pyridine (7.0 g, 32.68 mmol) in EtOH (200 mL) was added 10% Pd/C (0.7 g) and the resulting slurry was shaken under a H2 atmosphere (50 psi) using a Parr shaker. After 1 h, TLC and 1H-NMR of an aliquot indicated complete reaction. The mixture was filtered through a short pad of Celite®. The filtrate was concentrated in vacuo to afford a white solid (5.4 g, 90%): 1H-NMR (DMSO-d6) δ 3.74 (s, 2H), 4.91 (br s, 2H), 6.48 (d, J=8.46 Hz, 2H), 6.86 (d, J=8.09 Hz, 2H), 7.16 (d, J=5.88 Hz, 2H), 8.40 (d, J=5.88 Hz, 2H); EI-MS m/z 184 (M+). This material was used in urea formation reactions without further purification. A12. General Method for Substituted Aniline Formation via Dissolving Metal Reduction of a Nitroarene
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([OH:11])[CH:10]=1)[C:5]([OH:7])=[O:6].C(=O)([O-])[O-].[K+].[K+].[CH2:18](I)[CH:19]([CH3:21])[CH3:20].Cl>CN(C)C=O.O.C(OCC)(=O)C>[CH2:18]([O:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([O:11][CH2:3][CH:4]([CH3:8])[CH3:5])[CH:10]=1)[C:5]([O:7][CH2:18][CH:19]([CH3:21])[CH3:20])=[O:6])[CH:19]([CH3:21])[CH3:20]
Reactant: O=C(O)c1cc(O)cc(O)c1
Reactant: CC(C)CI
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Solvent: CCOC(C)=O
Product: CC(C)COC(=O)c1cc(OCC(C)C)cc(OCC(C)C)c1
Temperature: 110 °C
Reaction time: 7 h

Procedure:
In 50 ml of N,N-dimethylformamide are suspended 5.0 g of 3,5-dihydroxybenzoic acid, 29.8 g of potassium carbonate and 11 ml of isobutyl iodide. The mixture thus obtained is stirred at 110° C. for 7 hours. The reaction mixture is added to a mixture of ethyl acetate and water, pH is adjusted to 2 with 6 mol/L hydrochloric acid, and the organic layer is separated. The organic layer is washed with water and saturated aqueous solution of sodium chloride successively and dried over anhydrous magnesium sulfate, and then the solvent is distilled off under reduced pressure. The residue thus obtained is purified by silica gel column chromatography (eluent; hexane:ethyl acetate=10:1) to obtain 2.6 g of isobutyl 3,5-diisobutoxybenzoate as a light yellow oily product.
Reaction SMILES: [CH3:1][S:2][C:3]1[N:8]=[C:7]([NH:9][C:10]2([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[CH2:12][CH2:11]2)[C:6]([C:19]([NH2:21])=[O:20])=[CH:5][N:4]=1.C(OO)(C)=[O:23]>C(C#N)(C)=O>[CH3:1][S:2]([C:3]1[N:8]=[C:7]([NH:9][C:10]2([C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=3)[CH2:11][CH2:12]2)[C:6]([C:19]([NH2:21])=[O:20])=[CH:5][N:4]=1)=[O:23]
Reactant: CC(=O)OO
Reactant: CSc1ncc(C(N)=O)c(NC2(c3ccccc3)CC2)n1
Agent: CC(=O)C#N
Product: CS(=O)c1ncc(C(N)=O)c(NC2(c3ccccc3)CC2)n1
Temperature: 25 °C
Reaction time: 20 h

Procedure:
To a suspension of 2-(methylthio)-4-(1-phenylcyclopropylamino)pyrimidine-5-carboxamide (636 mg) in AcCN (3 mL) was added AcOOH (39% in AcOH, 0.7 mL). The mixture was stirred at room temperature for 20 h, and the solids were collected by filtration and dried in vacuo to give 2-(methylsulfinyl)-4-(1-phenylcyclopropylamino) pyrimidine-5-carboxamide (530 mg). MS 317.2 (M+H).
Reaction SMILES: [CH2:1]([NH2:13])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12].[CH2:14]([NH2:30])[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH3:29].[Cl:31][CH2:32][CH2:33][S:34]([N:37]=[C:38]=[O:39])(=[O:36])=[O:35]>>[CH2:1]([NH:13][C:38]([NH:37][S:34]([CH2:33][CH2:32][Cl:31])(=[O:36])=[O:35])=[O:39])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12].[CH2:14]([NH:30][C:38]([NH:37][S:34]([CH2:33][CH2:32][Cl:31])(=[O:36])=[O:35])=[O:39])[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH3:29]
Reactant: CCCCCCCCCCCCCCCCN
Reactant: O=C=NS(=O)(=O)CCCl
Reactant: CCCCCCCCCCCCN
Product: CCCCCCCCCCCCCCCCNC(=O)NS(=O)(=O)CCCl
Product: CCCCCCCCCCCCNC(=O)NS(=O)(=O)CCCl

Procedure:
Likewise it is possible to react 55.5 g (0.3 moles) of laurylamine or 72.3 g (0.3 moles) of hexadecylamine with 51.9 g (0.306 moles) of β-chlorethylsulphonyl isocyanate under the reaction conditions described to give N-lauryl-N'-β-chlorethylsulphonyl urea or N-hexadecyl-N'-β-chlorethylsulphonyl urea. N-lauryl-N'-β-chlorethylsulphonylurea:
Reaction SMILES: [S:1]1[CH:5]=[CH:4][CH:3]=[CH:2]1.C(OCC)C.[Li]CCCC.[CH:16]([C:18]1[N:23]2[CH:24]=[N:25][N:26]=[C:22]2[C:21]([N:27]2[CH2:32][CH2:31][N:30]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:29][CH2:28]2)=[N:20][CH:19]=1)=[O:17]>C(Cl)Cl>[OH:17][CH:16]([C:2]1[S:1][CH:5]=[CH:4][CH:3]=1)[C:18]1[N:23]2[CH:24]=[N:25][N:26]=[C:22]2[C:21]([N:27]2[CH2:32][CH2:31][N:30]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:29][CH2:28]2)=[N:20][CH:19]=1
Reactant: c1ccsc1
Reactant: CC(C)(C)OC(=O)N1CCN(c2ncc(C=O)n3cnnc23)CC1
Agent: [Li]CCCC
Solvent: CCOCC
Solvent: ClCCl
Product: CC(C)(C)OC(=O)N1CCN(c2ncc(C(O)c3cccs3)n3cnnc23)CC1
Temperature: 0 °C
Reaction time: 1 h
Yield: 72 %

Procedure:
A 250 mL 3-necked round bottom flask was charged with thiophene (0.63 g, 7.5 mmol) and dry ethyl ether (10 mL). To the above was added dropwise nBuLi solution (2.5 M in hexane, 3 mL, 7.5 mmol) at 0° C. The mixture was stirred at 0° C. for 1 h, and was then cooled to −78° C. A solution of tert-butyl 4-(5-formyl-[1,2,4]-triazolo[4,3-a]pyrazin-8-yl)piperazine-1-carboxylate (1.0 g, 3.0 mmol) in dry CH2Cl2 (10 mL) was added dropwise at that temperature. The resulting mixture was stirred at −78° C. for 0.5 h, and then quenched by slow addition of methanol (10 mL). The reaction mixture was poured into saturated aqueous NH4Cl (100 mL) and extracted with ethyl ether (100 mL×2). The combined organic layers were washed with saturated aqueous NaHCO3 (100 mL), dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was further purified by flash column chromatography on silica gel with 1% MeOH in CH2Cl2, to afford 0.90 g (72%) of the product as a white solid. MS m/z: 417 (M+H+).
Reaction SMILES: [N:1]1[C:8]([Cl:9])=[N:7][C:5](Cl)=[N:4][C:2]=1[Cl:3].[CH:10]([NH2:13])([CH3:12])[CH3:11].[OH-].[Na+]>>[Cl:9][C:8]1[N:1]=[C:2]([Cl:3])[N:4]=[C:5]([NH:13][CH:10]([CH3:12])[CH3:11])[N:7]=1
Reactant: Clc1nc(Cl)nc(Cl)n1
Reactant: CC(C)N
Agent: [Na+]
Agent: [OH-]
Product: CC(C)Nc1nc(Cl)nc(Cl)n1

Procedure:
In stage (a) cyanuric chloride, isopropylamine and sodium hydroxide are reacted to produce 2,4-dichloro-6-isopropylamino-s-triazine according to the following scheme: ##STR3##
Reaction SMILES: Cl[C:2]1[C:3]2[CH:30]=[C:29]([Cl:31])[CH:28]=[CH:27][C:4]=2[N:5]([CH2:18][C:19]2[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=2)[C:6](=[O:17])[CH:7]([CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[Cl:16])[N:8]=1.[Li+].[Cl-].CC1(C)C(C)(C)OB([C:42]2[CH:43]=[CH:44][C:45]([NH:48][C:49](=[O:51])[CH3:50])=[N:46][CH:47]=2)O1.O>O1CCOCC1>[Cl:31][C:29]1[CH:28]=[CH:27][C:4]2[N:5]([CH2:18][C:19]3[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=3)[C:6](=[O:17])[CH:7]([CH2:9][C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=3[Cl:16])[N:8]=[C:2]([C:42]3[CH:43]=[CH:44][C:45]([NH:48][C:49](=[O:51])[CH3:50])=[N:46][CH:47]=3)[C:3]=2[CH:30]=1
Reactant: CC(=O)Nc1ccc(B2OC(C)(C)C(C)(C)O2)cn1
Reactant: COc1ccc(CN2C(=O)C(Cc3ccccc3Cl)N=C(Cl)c3cc(Cl)ccc32)cc1
Agent: [Cl-]
Agent: [Li+]
Solvent: C1COCCO1
Solvent: O
Product: COc1ccc(CN2C(=O)C(Cc3ccccc3Cl)N=C(c3ccc(NC(C)=O)nc3)c3cc(Cl)ccc32)cc1
Temperature: 100 °C
Yield: 83.4 %

Procedure:
5,7-Dichloro-3-(2-chlorobenzyl)-1-(4-methoxybenzyl)-1H-benzo[e][1,4]diazepin-2(3H)-one (208 mg, 0.439 mmol), LiCl (56 mg, 1.32 mmol), and CsOH (221 mg, 1.32 mmol) were combined, then a solution of N-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl)acetamide (115 mg, 0.439 mmol) in 1,4-dioxane (3 mL) was added followed by water (300 uL). The mixture was purged with nitrogen, then tetrakis(triphenylphosphinepalladium(0) (51 mg, 0.044 mmol) was added and the flask was lowered into a 100° C. oil bath and heated at 100° C. for 3 h. The mixture was allowed to cool, then diluted with ethyl acetate and rinsed with water 2× then brine and dried (MgSO4). Chromatography eluting with 40-50% ethyl acetate in hexanes to give a colorless oil (210 mg, 83% yield). MS (ES+) m/z 573.1 (M+1).
Reaction SMILES: [S:1]([N:11]1[C:15]2=[N:16][CH:17]=[C:18]([CH2:20][NH:21][C:22]([CH:24]3[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]3)=S)[N:19]=[C:14]2[CH:13]=[CH:12]1)([C:4]1[CH:10]=[CH:9][C:7]([CH3:8])=[CH:6][CH:5]=1)(=[O:3])=[O:2]>C1COCC1.CCOC(C)=O.C(O[Hg]OC(=O)C)(=O)C>[CH:24]1([C:22]2[N:19]3[C:14]4[CH:13]=[CH:12][N:11]([S:1]([C:4]5[CH:10]=[CH:9][C:7]([CH3:8])=[CH:6][CH:5]=5)(=[O:3])=[O:2])[C:15]=4[N:16]=[CH:17][C:18]3=[CH:20][N:21]=2)[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]1
Reactant: Cc1ccc(S(=O)(=O)n2ccc3nc(CNC(=S)C4CCCCC4)cnc32)cc1
Agent: CC(=O)O[Hg]OC(C)=O
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: Cc1ccc(S(=O)(=O)n2ccc3c2ncc2cnc(C4CCCCC4)n23)cc1
Reaction time: 0.5 h
Yield: 25 %

Procedure:
To a solution of N #5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)methyl)cyclohexanecarboxamide (0.081 g, 0.196 mmol) in THF (1 mL) at ambient temperature was added 2,4-bis(4-phenoxyphenyl)-1,3-dithia-2,4-diphosphetane-2,4-disulfide (0.104 g, 0.196 mmol, TCI). After about 15 h, the reaction mixture was concentrated under reduced pressure. The residue was suspended in EtOAc/DCM (1:1) and filtered through a plug of silica gel (5 g) eluting with EtOAc/DCM (1:1, approximately 100 mL). Concentration of the filtrate provided the crude N-((5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)methyl)cyclohexanecarbothioamide. The crude thioamide was dissolved in THF (1 mL) and diacetoxymercury (0.0626 g, 0.196 mmol) was added. After about 30 min at ambient temperature, additional diacetoxymercury (0.0626 g, 0.196 mmol) was added. After about 4 h, the reaction mixture was diluted with EtOAc, filtered, concentrated under reduced pressure, and purified by silica gel chromatography eluting with a gradient of 50-95% EtOAc in heptane to provide 1-cyclohexyl-6-tosyl-6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazine as a yellow oil (0.020 g, 25%): LC/MS (Table 2, Method a) Rt=2.77 min; MS m/z: 395 (M+H)+.
Reaction SMILES: [CH2:1]([C@H:8]1[CH2:12][O:11][C:10](=[O:13])[NH:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([Li])CCC.[F:19][C:20]1[CH:25]=[CH:24][C:23]([CH2:26][C:27](Cl)=[O:28])=[CH:22][CH:21]=1.C(OCC)(=O)C.CCCCCC>O1CCCC1>[CH2:1]([C@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:27](=[O:28])[CH2:26][C:23]1[CH:24]=[CH:25][C:20]([F:19])=[CH:21][CH:22]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=C(Cl)Cc1ccc(F)cc1
Reactant: O=C1N[C@@H](Cc2ccccc2)CO1
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Solvent: CCCCCC
Product: O=C(Cc1ccc(F)cc1)N1C(=O)OC[C@@H]1Cc1ccccc1
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
Combine (S)-4-benzyl-2-oxazolidinone (22.9 g, 129 mmol) and tetrahydrofuran (120 mL). Cool in a dry-ice/acetone bath. Add dropwise a solution of n-butyl lithium (52 mL, 2.5 M, 130 mmol). After 15 minutes, slowly add a solution of 4-fluorophenylacetyl chloride (22.3 g, 129 mmol) in tetrahydrofuran (50 mL). Warm to ambient temperature. After 2 hours, quench the reaction mixture by the addition of a saturated aqueous sodium bicarbonate solution. Separate the layers and extract the aqueous layer with diethyl ether. Combine the organic layers, dry over Na2SO4, filter, and evaporate in vacuo to give a residue. Chromatograph the residue on silica gel eluting wit 15% ethyl acetate/hexane. Combine the product containing fractions, evaporate, and recrytallize from diethyl ether/hexane to give (S)-4-benzyl-3-(4-fluorophenyl)acetyl-2-oxazolidinone.