Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][CH:5]=[C:4]([Cl:11])[N:3]=1.C(N(CC)CC)C.[CH3:19][O:20][CH2:21][CH2:22][CH2:23][NH2:24]>ClCCl>[Cl:11][C:4]1[N:3]=[C:2]([NH:24][CH2:23][CH2:22][CH2:21][O:20][CH3:19])[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][CH:5]=1
Reactant: O=[N+]([O-])c1ccc(Cl)nc1Cl
Reactant: COCCCN
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COCCCNc1nc(Cl)ccc1[N+](=O)[O-]
Temperature: 25 °C
Yield: 91.5 %

Procedure:
2,6-Dichloro-3-nitropyridine (3.29 mmol, 0.635 g) was added to an oven dried 50 mL round-bottomed flask equipped for stirring under nitrogen. Dichlormethane (12 mL) and triethylamine (3.62 mmol, 0.504 mL) were added and the resultant solution was cooled to −15° C. with an acetone/ice bath. 3-methoxypropan-1-amine (3.29 mmol, 0.337 mL) was then added drop-wise via syringe and the resultant solution was stirred at −15° C. for 0.5 hr. The acetone/ice bath was removed and the reaction was allowed to warm to room temperature and stir for 0.5 hr. The reaction solution was poured into water and extracted twice with dichloromethane (50 mL). The organic layer was collected and subsequently dried with anhydrous Na2SO4 and filtered. This filtrate was collected, concentrated, and dried in-vacuo affording an orange oil. This material was then purified by chromatography on silica gel (20% ethyl acetate/hexanes) to afford 6-chloro-N-(3-methoxypropyl)-3-nitropyridin-2-amine (33A) as a yellow solid (3.01 mmol, 0.740 g, 92% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.79-1.89 (m, 2H) 3.00 (s, 3H) 3.43 (t, J=6.06 Hz, 2H) 3.53-3.61 (m, 2H) 6.77 (d, J=8.59 Hz, 1H) 8.42 (d, J=8.08 Hz, 1H). ESI-MS: m/z 246.2 (M+H)+.
Reaction SMILES: Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([CH:12]=1)[C:7]([O:9][CH2:10][CH3:11])=[O:8].[F:13][C:14]([F:26])([F:25])[O:15][C:16]1[CH:21]=[CH:20][C:19](B(O)O)=[CH:18][CH:17]=1.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.O.CN(C)C=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:13][C:14]([F:25])([F:26])[O:15][C:16]1[CH:21]=[CH:20][C:19]([C:2]2[CH:12]=[C:6]([C:7]([O:9][CH2:10][CH3:11])=[O:8])[CH:5]=[N:4][CH:3]=2)=[CH:18][CH:17]=1
Reactant: OB(O)c1ccc(OC(F)(F)F)cc1
Reactant: CCOC(=O)c1cncc(Br)c1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: COCCOC
Solvent: CN(C)C=O
Product: CCOC(=O)c1cncc(-c2ccc(OC(F)(F)F)cc2)c1
Temperature: 85 °C
Reaction time: 18 h

Procedure:
3.35 g (14.6 mmol) of ethyl 5-bromonicotinate, 4.50 g (21.9 mmol) of 4-(trifluoromethoxy)-phenylboronic acid, 0.84 g (0.73 mmol) of tetrakis(triphenylphosphine)palladium(0) and 3.01 g (29.1 mmol) of sodium carbonate were dissolved in a mixture of 38 ml of 1,2-dimethoxyethane, 7.5 ml of water and 91 ml of dimethylformamide and stirred at 85° C. for 18 h. For work-up, some of the dimethylformamide was removed under reduced pressure, and the reaction mixture was diluted with water and extracted with dichloromethane. The organic phase was dried over sodium sulphate and the crude product was purified by flash chromatography (dichloromethane/acetonitrile 100:0→100:5). Yield: 2.64 g (55% of theory)
Reaction SMILES: [CH3:1][C:2]1[S:6][C:5]([C:7]([OH:9])=O)=[N:4][CH:3]=1.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.[NH:24]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[NH2:25]>ClCCl>[CH3:1][C:2]1[S:6][C:5]([C:7]([NH:25][NH:24][C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])=[O:9])=[N:4][CH:3]=1
Reactant: CC(C)(C)OC(=O)NN
Reactant: Cc1cnc(C(=O)O)s1
Agent: On1nnc2ccccc21
Solvent: ClCCCl
Solvent: ClCCl
Product: Cc1cnc(C(=O)NNC(=O)OC(C)(C)C)s1
Reaction time: 0.25 h

Procedure:
A solution of 5-methyl-1,3-thiazole-2-carboxylic acid (500 mg, 3.49 mmol) in dry dichloromethane (DCM) (17.500 ml) was stirred at room temperature under an atmosphere of argon. EDC (803 mg, 4.19 mmol) and HOBT (267 mg, 1.746 mmol) were added to the stirred solution. After 15 minutes, 1,1-dimethylethyl hydrazinecarboxylate (554 mg, 4.19 mmol) was added to the stirred solution. The resulting solution was stirred for 18 hours. After this time, the solution was diluted with DCM (approx. 50 ml) and washed with water (2× approx. 20 ml). The organic extracts were dried over MgSO4, filtered and concentrated under reduced pressure to give a yellow coloured oil of desired product in 451 mg.
Reaction SMILES: [C:1]([C:3]1[CH:4]=[C:5]([NH:9][C:10](=[O:33])[NH:11][C:12]2[CH:17]=[CH:16][C:15]([S:18]([NH:21][CH2:22][C:23]3[CH:28]=[CH:27][C:26]([S:29](=[O:32])(=[O:31])[NH2:30])=[CH:25][CH:24]=3)(=[O:20])=[O:19])=[CH:14][CH:13]=2)[CH:6]=[CH:7][CH:8]=1)#[N:2].[CH:34]([N:37]1[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]1)([CH3:36])[CH3:35]>>[NH:2]=[C:1]([N:40]1[CH2:41][CH2:42][N:37]([CH:34]([CH3:36])[CH3:35])[CH2:38][CH2:39]1)[C:3]1[CH:4]=[C:5]([NH:9][C:10](=[O:33])[NH:11][C:12]2[CH:17]=[CH:16][C:15]([S:18]([NH:21][CH2:22][C:23]3[CH:28]=[CH:27][C:26]([S:29](=[O:32])(=[O:31])[NH2:30])=[CH:25][CH:24]=3)(=[O:20])=[O:19])=[CH:14][CH:13]=2)[CH:6]=[CH:7][CH:8]=1
Reactant: CC(C)N1CCNCC1
Reactant: N#Cc1cccc(NC(=O)Nc2ccc(S(=O)(=O)NCc3ccc(S(N)(=O)=O)cc3)cc2)c1
Product: CC(C)N1CCN(C(=N)c2cccc(NC(=O)Nc3ccc(S(=O)(=O)NCc4ccc(S(N)(=O)=O)cc4)cc3)c2)CC1
Yield: 3 %

Procedure:
The title compound was prepared from 4-(3-(3-cyanophenyl)ureido)-N-(4-sulfamoylbenzyl)benzenesulfonamide following procedure C and using 1.5 equivalents of 1-isopropylpiperazine as secondary amine. The product was purified by preparative HPLC.
Reaction SMILES: SCCC[Si](OC)(OC)OC.OCCOCCOCCOCC[N:24]([CH2:26][CH2:27][CH2:28][Si:29]([O:40][CH2:41]CCC)([O:35][CH2:36]CCC)[O:30][CH2:31]CCC)C>>[NH2:24][CH2:26][CH2:27][CH2:28][Si:29]([O:40][CH3:41])([O:30][CH3:31])[O:35][CH3:36]
Reactant: CCCCO[Si](CCCN(C)CCOCCOCCOCCO)(OCCCC)OCCCC
Agent: CO[Si](CCCS)(OC)OC
Product: CO[Si](CCCN)(OC)OC

Procedure:
##STR10## HSCH2CH2CH2Si(OCH3)3 ; HO(C2H4O)3C2H4N(CH3)(CH2)3Si(OC4H9)3 ;
Reaction SMILES: F[C:2]1[C:3]([C:9]#[N:10])=[N:4][C:5]([F:8])=[CH:6][N:7]=1.[C:11]1([CH:18]=[CH:17][C:15]([OH:16])=[CH:14][CH:13]=1)[OH:12].C(=O)([O-])[O-].[K+].[K+].Cl>CN(C)C=O.O.C(OCC)(=O)C>[F:8][C:5]1[N:4]=[C:3]([C:9]#[N:10])[C:2]([O:12][C:11]2[CH:18]=[CH:17][C:15]([OH:16])=[CH:14][CH:13]=2)=[N:7][CH:6]=1
Reactant: Oc1ccc(O)cc1
Reactant: N#Cc1nc(F)cnc1F
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Solvent: O
Product: N#Cc1nc(F)cnc1Oc1ccc(O)cc1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 15.3 %

Procedure:
In 30 mL of dimethylformamide was dissolved 3.0 g of 3,6-difluoro-2-pyrazinecarbonitrile. Then, 2.6 g of hydroquinone, followed by 6.5 g of potassium carbonate, was added at an ice-cooled temperature, and the mixture thus obtained was stirred at room temperature for 15 minutes. A mixture of 30 mL of ethyl acetate and 60 ml of water was added to the reaction mixture, pH was adjusted to 5 with 6 mol/L hydrochloric acid, and the organic layer was separated. The organic layer thus obtained was washed successively with water and saturated aqueous solution of sodium chloride and dried on anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The residue thus obtained was purified by silica gel column chromatography [eluent: n-hexane:ethyl acetate=3:1] to obtain 0.75 g of 6-fluoro-3-(4-hydroxyphenoxy)-2-pyrazinecarbonitrile as a yellow-colored solid product.
Reaction SMILES: [CH3:1][C:2]1[CH:17]=[CH:16][C:5]([CH2:6][C:7]2[C:15]3[S:14][CH:13]=[CH:12][C:11]=3[CH:10]=[CH:9][CH:8]=2)=[CH:4][CH:3]=1.[Br:18]N1C(=O)CCC1=O>C(#N)C>[Br:18][C:12]1[C:11]2[CH:10]=[CH:9][CH:8]=[C:7]([CH2:6][C:5]3[CH:4]=[CH:3][C:2]([CH3:1])=[CH:17][CH:16]=3)[C:15]=2[S:14][CH:13]=1
Reactant: O=C1CCC(=O)N1Br
Reactant: Cc1ccc(Cc2cccc3ccsc23)cc1
Solvent: CC#N
Product: Cc1ccc(Cc2cccc3c(Br)csc23)cc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 55.8 %

Procedure:
An acetonitrile (30 mL) solution of 7-(4-methylbenzyl)-1-benzothiophene (1.24 g, 5.20 mmol) was added with N-bromosuccinimide (1.01 g, 5.72 mmol) and stirred at room temperature for two hours. The solvent was evaporated under reduced pressure and diluted with ethyl acetate. After washed with 20 wt % sodium thiosulfate aqueous solution and brine, the organic phase was dried with anhydrous magnesium sulfate. After the desiccant was filtered off, the residue obtained by evaporating the solvent under reduced pressure was purified by silica gel column chromatography (hexane:ethyl acetate=100:1-50:1) to obtain a colorless powdered title compound (0.92 g, 56%).
Reaction SMILES: [CH2:1]([N:8]1[C:16](=[O:17])[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH:9]1[CH2:18][CH2:19]C(NC1SC=CN=1)=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[N-:28]=[N+:29]=[N-:30].[Na+].C([O-])([O-])=O.[K+].[K+].O>CN(C=O)C>[N:28]([CH2:19][CH2:18][CH:9]1[C:10]2[C:15](=[CH:14][CH:13]=[CH:12][CH:11]=2)[C:16](=[O:17])[N:8]1[CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)=[N+:29]=[N-:30]
Reactant: [N-]=[N+]=[N-]
Reactant: O=C(CCC1c2ccccc2C(=O)N1Cc1ccccc1)Nc1nccs1
Agent: O=C([O-])[O-]
Agent: [K+]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: [N-]=[N+]=NCCC1c2ccccc2C(=O)N1Cc1ccccc1

Procedure:
The product from Example 1, Part B (2.0 g, 7.5 mmol), sodium azide (731 mg, 11.25 mmol), and K2CO3 (3.1 g, 225 mmol) were stirred in 20 mL DMF at 50° C. for 16 h. The mixture was poured into water and washed with EtOAc. The organic phase was washed with water and brine, then dried (Na2SO4), filtered and evaporated. The title compound was purified by silica gel chromatography (2.04 g, 93%).
Reaction SMILES: [CH2:1]([O:5][CH:6]([O:8][NH:9][C:10]([C:12]1[CH:13]=[N:14][C:15]([N:18]2[CH2:23][CH:22]3[CH:20]([CH:21]3[NH:24][CH2:25][C:26]3[CH:35]=[CH:34][C:33]4[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=4)[CH:27]=3)[CH2:19]2)=[N:16][CH:17]=1)=[O:11])[CH3:7])[CH:2]([CH3:4])[CH3:3].[H-].[Na+].Br[CH2:39][CH2:40][N:41]([CH2:44][CH3:45])[CH2:42][CH3:43]>CN(C=O)C>[CH2:1]([O:5][CH:6]([O:8][NH:9][C:10]([C:12]1[CH:13]=[N:14][C:15]([N:18]2[CH2:19][CH:20]3[CH:22]([CH:21]3[N:24]([CH2:39][CH2:40][N:41]([CH2:44][CH3:45])[CH2:42][CH3:43])[CH2:25][C:26]3[CH:35]=[CH:34][C:33]4[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=4)[CH:27]=3)[CH2:23]2)=[N:16][CH:17]=1)=[O:11])[CH3:7])[CH:2]([CH3:4])[CH3:3]
Reactant: CC(C)COC(C)ONC(=O)c1cnc(N2CC3C(C2)C3NCc2ccc3ccccc3c2)nc1
Reactant: CCN(CC)CCBr
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCN(CC)CCN(Cc1ccc2ccccc2c1)C1C2CN(c3ncc(C(=O)NOC(C)OCC(C)C)cn3)CC21
Reaction time: 0.25 h
Yield: 28.5 %

Procedure:
N-(1-Isobutoxyethoxy) 2-{6-[(naphthalen-2-ylmethyl)-amino]-3-azabicyclo[3.1.0]hex-3-yl}-pyrimidine-5-carboxamide (52 mg, 0.11 mmol) was dissolved in anhydrous DMF (2 ml) and cooled over ice. To the solution was added sodium hydride (13 mg, 0.55 mmol-60% dispersion in mineral oil) and the mixture was stirred for 15 min. To the stirring mixture was then added (2-bromoethyl)-N,N-diethylamine (22 mg, 0.12 mmol). After stirring for 30 min, the reaction was quenched by the careful addition of water and stirred for 10 min. The aqueous mixture was extracted with EtOAc (3×20 ml) and the combined organic extracts were washed with brine, dried (MgSO4) and evaporated to dryness to give the title compound as a white solid (18 mg, 29%). LCMS purity 100%, m/z 575 [M+H]+.
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[C:7]([NH2:26])=[C:8](C(OC(C)(C)C)=O)[N:9]([C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[C:13]([F:18])[CH:12]=2)[CH:10]=1)=[O:5])[CH3:2].[CH2:27]([N:29]=[C:30]=[O:31])[CH3:28]>>[CH2:1]([O:3][C:4]([C:6]1[C:7]([NH:26][C:30]([NH:29][CH2:27][CH3:28])=[O:31])=[CH:8][N:9]([C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[C:13]([F:18])[CH:12]=2)[CH:10]=1)=[O:5])[CH3:2]
Reactant: CCOC(=O)c1cn(-c2ccc(Cl)c(F)c2)c(C(=O)OC(C)(C)C)c1N
Reactant: CCN=C=O
Product: CCNC(=O)Nc1cn(-c2ccc(Cl)c(F)c2)cc1C(=O)OCC
Yield: 76 %

Procedure:
Following general method 4, employing 3-amino-1-(4-chloro-3-fluoro-phenyl)-1H-pyrrole-2,4-dicarboxylic acid 2-tert-butyl ester 4-ethyl ester and ethyl isocyanate, afforded the title compound as a yellow solid (0.65 g, 76%); LCMS (method B): RT=3.87 min, M+H+=354; 1H NMR (DMSO-D6, 400 MHz): 8.27 (s, 1H), 7.91 (d, J=2.7 Hz, 1H), 7.86 (dd, J=10.9, 2.6 Hz, 1H), 7.68-7.63 (m, 2H), 7.54-7.50 (m, 1H), 7.23 (t, J=5.3 Hz, 1H), 4.28 (q, J=7.1 Hz, 2H), 3.13-3.05 (m, 2H), 1.31 (t, J=7.1 Hz, 3H), 1.05 (t, J=7.2 Hz, 3H).
Reaction SMILES: [C:1]([C@@H:3]([NH:22][C:23]([C@@H:25]1[CH2:30][CH2:29][CH2:28][CH2:27][N:26]1C(OC(C)(C)C)=O)=[O:24])[CH2:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:16]=[CH:15][C:14]([C:17]#[N:18])=[C:13]([S:19]([CH3:21])=[O:20])[CH:12]=2)=[CH:7][CH:6]=1)#[N:2].C(O)=[O:39]>>[C:17]([C:14]1[CH:15]=[CH:16][C:11]([C:8]2[CH:9]=[CH:10][C:5]([CH2:4][C@H:3]([NH:22][C:23]([C@@H:25]3[CH2:30][CH2:29][CH2:28][CH2:27][NH:26]3)=[O:24])[C:1]#[N:2])=[CH:6][CH:7]=2)=[CH:12][C:13]=1[S:19]([CH3:21])=[O:20])(=[O:39])[NH2:18]
Reactant: O=CO
Reactant: CS(=O)c1cc(-c2ccc(C[C@@H](C#N)NC(=O)[C@@H]3CCCCN3C(=O)OC(C)(C)C)cc2)ccc1C#N
Product: CS(=O)c1cc(-c2ccc(C[C@@H](C#N)NC(=O)[C@@H]3CCCCN3)cc2)ccc1C(N)=O
Temperature: 50 °C

Procedure:
A solution of (2S)-tert-butyl 2-((1S)-1-cyano-2-(4′-cyano-3′-(methylsulfinyl)biphenyl-4-yl)ethylcarbamoyl)piperidine-1-carboxylate (0.08 g) in formic acid (2 mL) was stirred and heated at 50° C. for 10 min. The mixture was evaporated and applied to a 10 g SCX column. The column was washed with methanol then eluted with 10% ammonia in methanol. The eluate was evaporated and the residue dissolved in isopropanol and precipitated with diethyl ether. The solid was collected, washed with diethyl ether and dried over magnesium sulfate. Purification by RPHPLC using aqueous 0.1% TFA afforded the major product as a colourless solid (0.027 g).
Reaction SMILES: [F:1][C:2]1[C:7]([CH2:8][CH2:9][OH:10])=[CH:6][C:5]([C:11]2[S:12][CH:13]=[C:14]([CH3:16])[CH:15]=2)=[CH:4][N:3]=1.Cl[C:18]1[C:27]2[C:22](=[CH:23][C:24]([O:28][CH3:29])=[CH:25][CH:26]=2)[N:21]=[CH:20][CH:19]=1.C(P(C(C)(C)C)C1C=CC2C(=CC=CC=2)C=1C1C2C(=CC=CC=2)C=CC=1)(C)(C)C.C(=O)([O-])[O-].[Cs+].[Cs+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(C)C=CC=CC=1>[F:1][C:2]1[C:7]([CH2:8][CH2:9][O:10][C:18]2[C:27]3[C:22](=[CH:23][C:24]([O:28][CH3:29])=[CH:25][CH:26]=3)[N:21]=[CH:20][CH:19]=2)=[CH:6][C:5]([C:11]2[S:12][CH:13]=[C:14]([CH3:16])[CH:15]=2)=[CH:4][N:3]=1
Reactant: Cc1csc(-c2cnc(F)c(CCO)c2)c1
Reactant: COc1ccc2c(Cl)ccnc2c1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: CC(C)(C)P(c1ccc2ccccc2c1-c1cccc2ccccc12)C(C)(C)C
Solvent: Cc1ccccc1
Product: COc1ccc2c(OCCc3cc(-c4cc(C)cs4)cnc3F)ccnc2c1
Temperature: 80 °C

Procedure:
To a 5 mL CEM microwave tube was added 2-(2-fluoro-5-(4-methylthiophen-2-yl)pyridin-3-yl)ethanol (0.06 g, 0.3 mmol), 4-chloro-7-methoxyquinoline (0.10 g, 0.5 mmol), racemic-2-(di-t-butylphosphino)-1,1′-binaphthyl (0.04 g, 0.1 mmol), palladium (II) acetate (0.02 g, 0.1 mmol), cesium carbonate (0.2 g, 0.5 mmol), and toluene (4 mL). The vial was sealed and heated at 80° C. in the closed system for 3 h. The reaction mixture was passed through the celite to separate the inorganic salt. Solvent was removed. The crude product was purified using SiO2 chromatography with CH2Cl2:MeOH (98%:2%) to afford the product as brown solid. MS (ESI pos. ion) m/z (MH+): 395.3. Calc'd exact mass for C22H19FN2O2S: 394.1. 1H NMR (300 MHz, Chloroform-d) δ ppm 2.30 (s, 3 H) 3.31 (t, J=6.21 Hz, 2 H) 3.94 (s, 3 H) 4.46 (t, J=6.21 Hz, 2 H) 6.65 (d, J=5.41 Hz, 1 H) 6.94 (s, 1 H) 7.07 (s, 1 H) 7.12 (dd, J=9.13, 2.56 Hz, 1 H) 7.36 (d, J=2.48 Hz, 1 H) 7.95 (dd, J=8.99, 2.41 Hz, 1 H) 8.05 (d, J=9.06 Hz, 1 H) 8.33 (s, 1 H) 8.67 (d, J=5.26 Hz, 1 H).
Reaction SMILES: [CH:1]1([C:4]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)([C:6]2[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=2)O)[CH2:3][CH2:2]1.[BrH:18]>>[Br:18][CH2:3][CH2:2][CH:1]=[C:4]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1
Reactant: Br
Reactant: OC(c1ccccc1)(c1ccccc1)C1CC1
Product: BrCCC=C(c1ccccc1)c1ccccc1
Temperature: 25 °C
Reaction time: 3 h
Yield: 97 %

Procedure:
A mixture of 26,5 g of α-cyclopropyl-α-phenylbenzenemethanol and 150 ml of 48% HBr was stirred at ambient temperature for 3 h. After addition of icewater, the mixture was extracted twice with diethyl ether, washed, dried and concentrated to obtain 33 g (97,3%) of 4-bromo-1,1-diphenyl-1-butene.
Reaction SMILES: S(C1C=CC(C)=CC=1)(O[CH2:5][CH2:6][C:7]([F:10])([F:9])[F:8])(=O)=O.[OH:18][C:19]1[CH:20]=[C:21]([CH:24]=[CH:25][CH:26]=1)[CH:22]=[O:23].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.O>[F:8][C:7]([F:10])([F:9])[CH2:6][CH2:5][O:18][C:19]1[CH:20]=[C:21]([CH:24]=[CH:25][CH:26]=1)[CH:22]=[O:23]
Reactant: O=Cc1cccc(O)c1
Reactant: Cc1ccc(S(=O)(=O)OCCC(F)(F)F)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: O=Cc1cccc(OCCC(F)(F)F)c1
Temperature: 25 °C
Reaction time: 18 h

Procedure:
Combine 3,3,3-trifluoropropyl tosylate (4.057 gm; 15.12 mmol), 3-hydroxybenzaldehyde (1.85 gm; 15.12 mmol), and K2CO3 (4.15 gm; 30.0 mmol) in DMF (80 mL) and heat at 100° C. After 18 hours, cool to room temperature, dilute with water (200 mL) and extract with dichloromethane (2×200 mL). Combine organic extracts and wash sequentially with water (100 mL), 0.1 M NaOH (2×100 mL), saturated sodium bicarbonate (100 mL) and saturated brine (100 mL), dry (MgSO4), and concentrate. Chromatography on silica gel (0–20% ethyl acetate in hexane) to give the title product.
Reaction SMILES: [C:1]1([S:11]([OH:13])=[O:12])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.[OH-].[Na+].[CH:16]([S:18](Cl)(=[O:20])=[O:19])=[CH2:17]>O>[CH:16]([S:18](=[O:20])(=[O:19])[S:11]([C:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1)(=[O:13])=[O:12])=[CH2:17]
Reactant: C=CS(=O)(=O)Cl
Reactant: O=S(O)c1cccc2ccccc12
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: C=CS(=O)(=O)S(=O)(=O)c1cccc2ccccc12
Yield: 24.9 %

Procedure:
15 ml of water was added to 9.6 g of 1-naphthalene sulfinic acid and a solution of 2 g of sodium hydroxide in 5 ml of water was added to the mixture. To the solution there was added a solution of 6.3 g of vinylsulfonyl chloride in 20 ml of acetronitrile at room temperature with stirring and the mixture was stirred at room temperature for additional 24 hours. The reaction solution was poured into 300 ml of water, the resulting precipitates were recovered through filtration and recrystallized from a mixed solvent of benzene and ethanol to give 3.5 g of vinyl-1-naphthyldisulfone.
Reaction SMILES: [CH3:1][N:2]1[CH:6]=[CH:5][CH:4]=[C:3]1[Sn](C)(C)C.Br[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[N+:18]([O-:20])=[O:19]>>[CH3:1][N:2]1[CH:6]=[CH:5][CH:4]=[C:3]1[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[N+:18]([O-:20])=[O:19]
Reactant: Cn1cccc1[Sn](C)(C)C
Reactant: O=[N+]([O-])c1ccccc1Br
Product: Cn1cccc1-c1ccccc1[N+](=O)[O-]
Yield: 68.6 %

Procedure:
1-Methyl-2-(trimethylstannyl)-1H-pyrrole (3.94 g, 14.7 mmol) and 1-bromo-2-nitrobenzene (3.22 g, 15.9 mmol, 1.08 eq) were coupled as in Example 75 to give 2.04 g of 1-methyl-2-(2-nitrophenyl)-1H-pyrrole, which was reduced as in Example 64 to give 1.53 g of 2-(1-methyl-1H-pyrrol-2-yl)aniline.
Reaction SMILES: [C:1]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])(=[O:8])[CH2:2][C:3]([O:5][CH2:6][CH3:7])=[O:4].[H-].[Na+].Cl.[CH3:17][Si:18]([CH3:44])([CH3:43])[CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][NH:33][C:34]1[CH:42]=[CH:41][C:37]([C:38](Cl)=[O:39])=[CH:36][CH:35]=1>COCCOC>[CH3:44][Si:18]([CH3:17])([CH3:43])[CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][NH:33][C:34]1[CH:35]=[CH:36][C:37]([C:38]([CH:2]([C:3]([O:5][CH2:6][CH3:7])=[O:4])[C:1]([O:9][C:10]([CH3:12])([CH3:11])[CH3:13])=[O:8])=[O:39])=[CH:41][CH:42]=1
Reactant: C[Si](C)(C)CCCCCCCCCCCCCCNc1ccc(C(=O)Cl)cc1
Reactant: CCOC(=O)CC(=O)OC(C)(C)C
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: COCCOC
Product: CCOC(=O)C(C(=O)OC(C)(C)C)C(=O)c1ccc(NCCCCCCCCCCCCCC[Si](C)(C)C)cc1

Procedure:
A solution of 14 g. of tert-butyl ethyl malonate in 5 ml. of 1,2-dimethoxyethane is added to a suspension of 2.0 g. of sodium hydride in 1,2-dimethoxyethane under argon. A solution of 8.4 g. of 4-[14-(trimethylsilyl)tetradecylamino]benzoyl chloride hydrochloride in 1,2-dimethoxyethane is then added. The reaction mixture is refluxed for 5 hours, cooled, poured on ice and extracted with ether. The ether solution is washed with water and saturated sodium chloride solution, dried with anhydrous sodium sulfate and evaporated to dryness. The residue is then recrystallized to yield the title compound.
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]2([CH2:13][O:12][C:11]3[CH:14]=[C:15]4[C:19](=[CH:20][C:10]2=3)[CH2:18][CH2:17][O:16]4)[C:2]1=[O:21].Cl[CH2:23][C:24]1[O:25][CH:26]=[C:27]([C:29]([O:31][CH3:32])=[O:30])[N:28]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CC(=O)CC>[O:21]=[C:2]1[C:3]2([CH2:13][O:12][C:11]3[CH:14]=[C:15]4[C:19](=[CH:20][C:10]2=3)[CH2:18][CH2:17][O:16]4)[C:4]2[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=2)[N:1]1[CH2:23][C:24]1[O:25][CH:26]=[C:27]([C:29]([O:31][CH3:32])=[O:30])[N:28]=1
Reactant: COC(=O)c1coc(CCl)n1
Reactant: O=C1Nc2ccccc2C12COc1cc3c(cc12)CCO3
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CCC(C)=O
Product: COC(=O)c1coc(CN2C(=O)C3(COc4cc5c(cc43)CCO5)c3ccccc32)n1
Temperature: 25 °C
Yield: 63.7 %

Procedure:
A suspended mixture of 5,6-dihydrospiro[benzo[1,2-b:5,4-b′]difuran-3,3′-indol]-2′(1′H)-one (1.00 g, 3.3 mmol), methyl 2-(chloromethyl)oxazole-4-carboxylate (2.00 g, 11.4 mmol) and cesium carbonate (4.00 g, 12.3 mmol) in butanone (50 mL) was refluxed for 5 h under nitrogen. The reaction mixture was cooled to ambient temperature and filtered. The solid was washed with acetone (50 mL). The filtrate was concentrated in vacuo to dryness. The residue was purified by column chromatography with a 30% to 70% gradient of ethyl acetate in hexanes to afford methyl 2-[(2′-oxo-5,6-dihydrospiro[benzo[1,2-b:5,4-b′]difuran-3,3′-indol]-1′(2′H)-yl)methyl]-1,3-oxazole-4-carboxylate (0.88 g, 61%) as a colorless solid: 1H NMR (300 MHz, DMSO-d6) δ 8.17 (s, 1H), 7.27-6.91 (m, 4H), 6.53 (s, 1H), 6.38 (s, 1H), 5.12 (ABq, 2H), 4.81 (ABq 2H), 4.51 (t, J=8.7 Hz, 2H), 3.89 (s, 3H), 3.04-2.91 (m, 2H); 13C NMR (75 MHz, DMSO-d6) δ 8177.6, 161.9, 161.2, 161.2, 159.2, 145.0, 141.0, 133.6, 132.5, 129.0, 124.1, 120.1, 119.9, 199.1, 108.8, 93.2, 80.5, 72.4, 57.7, 52.3, 37.2, 29.0; MS (ES+) m/z 419.2 (M+1).
Reaction SMILES: Cl.[CH3:2][O:3][C:4]1[CH:5]=[CH:6][C:7]([O:13][CH2:14][CH2:15][CH3:16])=[C:8]([CH:12]=1)[C:9]([NH2:11])=[NH:10].[O:17]=[C:18]1NC(C2C=CC=CC=2OCC=C)=N[CH:20]=[C:19]1[C:34]([O:36][CH2:37][CH3:38])=[O:35]>>[O:17]=[C:18]1[NH:11][C:9]([C:8]2[CH:12]=[C:4]([O:3][CH3:2])[CH:5]=[CH:6][C:7]=2[O:13][CH2:14][CH2:15][CH3:16])=[N:10][CH:20]=[C:19]1[C:34]([O:36][CH2:37][CH3:38])=[O:35]
Reactant: CCCOc1ccc(OC)cc1C(=N)N
Reactant: C=CCOc1ccccc1-c1ncc(C(=O)OCC)c(=O)[nH]1
Agent: Cl
Product: CCCOc1ccc(OC)cc1-c1ncc(C(=O)OCC)c(=O)[nH]1

Procedure:
The title compound was prepared from 5-methoxy-2 -n-propoxybenzamidine hydrochloride in a manner similar to that described for the preparation of ethyl 1,6-dihydro-6 -oxo-2-(2-allyloxyphenyl)pyrimidine-5-carboxylate in Preparation 29. The product had m.p. 124°-126°.