Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]1([N:7]2[C:11]([NH:12][C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)=[CH:10][C:9]([CH2:19][OH:20])=[N:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(N(CC)CC)C.O>CS(C)=O>[C:1]1([N:7]2[C:11]([NH:12][C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=3)=[CH:10][C:9]([CH:19]=[O:20])=[N:8]2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: OCc1cc(Nc2ccccc2)n(-c2ccccc2)n1
Solvent: CS(C)=O
Solvent: CCN(CC)CC
Solvent: O
Product: O=Cc1cc(Nc2ccccc2)n(-c2ccccc2)n1
Temperature: 25 °C
Reaction time: 18 h
Yield: 75.4 %

Procedure:
[1-Phenyl-5-(phenylamino)-1H-pyrazol-3-yl]methanol (318 mg) and triethylamine (1 mL) were dissolved in dimethyl sulfoxide (5 mL), and sulfur trioxide•pyridine complex (535 mg) was added at room temperature. After stirring at room temperature for 18 hr, water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent:hexane-ethyl acetate=7:1→3:1) to give the title compound as a pale-yellow powder (yield 238 mg, yield 81%).
Reaction SMILES: [Br:1][C:2]1[CH:27]=[CH:26][C:5]([CH2:6][C:7]23[C:15](=[O:16])[N:14]([C:17]4[CH:22]=[C:21]([Cl:23])[CH:20]=[C:19]([Cl:24])[CH:18]=4)[C:13](=[O:25])[N:12]2[CH2:11][CH2:10][NH:9][CH2:8]3)=[CH:4][CH:3]=1.[CH2:28]=O>C(O)=O.O.CCOC(C)=O>[CH3:28][N:9]1[CH2:8][C:7]2([CH2:6][C:5]3[CH:26]=[CH:27][C:2]([Br:1])=[CH:3][CH:4]=3)[N:12]([C:13](=[O:25])[N:14]([C:17]3[CH:22]=[C:21]([Cl:23])[CH:20]=[C:19]([Cl:24])[CH:18]=3)[C:15]2=[O:16])[CH2:11][CH2:10]1
Reactant: O=C1N(c2cc(Cl)cc(Cl)c2)C(=O)C2(Cc3ccc(Br)cc3)CNCCN12
Reactant: C=O
Solvent: O=CO
Solvent: O
Solvent: CCOC(C)=O
Product: CN1CCN2C(=O)N(c3cc(Cl)cc(Cl)c3)C(=O)C2(Cc2ccc(Br)cc2)C1

Procedure:
To a solution of 6-(4-bromobenzyl)-8-(3,5-dichlorophenyl)-1,4,8-triazabicyclo[4.3.0]nonane-7,9-dione (0.072 g) in formic acid (0.40 mL) and water (0.10 mL) was added 37% formaldehyde (0.050 mL). After 1 hour at reflux, the reaction mixture was diluted with EtOAc and the solution washed with aqueous NaHCO3, and brine, dried (Na2SO4), filtered, and concentrated to yield the titled compound (74.3 g). MS (m/z) 482 (MH+). mp 221° C.
Reaction SMILES: Cl.[CH2:2]([NH:4][C:5]([NH:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[N:15]=[C:16]([N:24]3[CH2:29][CH2:28][O:27][CH2:26][C@@H:25]3[CH3:30])[C:17]3[CH2:23][NH:22][CH2:21][CH2:20][C:18]=3[N:19]=2)=[CH:10][CH:9]=1)=[O:6])[CH3:3].CN(C)C=O.C(N(CC)C(C)C)(C)C.[CH:45]1([S:48](Cl)(=[O:50])=[O:49])[CH2:47][CH2:46]1>>[CH:45]1([S:48]([N:22]2[CH2:21][CH2:20][C:18]3[N:19]=[C:14]([C:11]4[CH:12]=[CH:13][C:8]([NH:7][C:5]([NH:4][CH2:2][CH3:3])=[O:6])=[CH:9][CH:10]=4)[N:15]=[C:16]([N:24]4[CH2:29][CH2:28][O:27][CH2:26][C@@H:25]4[CH3:30])[C:17]=3[CH2:23]2)(=[O:50])=[O:49])[CH2:47][CH2:46]1
Reactant: O=S(=O)(Cl)C1CC1
Reactant: CCNC(=O)Nc1ccc(-c2nc3c(c(N4CCOC[C@@H]4C)n2)CNCC3)cc1
Agent: Cl
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: CCNC(=O)Nc1ccc(-c2nc3c(c(N4CCOC[C@@H]4C)n2)CN(S(=O)(=O)C2CC2)CC3)cc1
Reaction time: 2 h

Procedure:
(S)-1-ethyl-3-(4-(4-(3-methylmorpholino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)phenyl)urea hydrochloride (0.1000 g, 0.2310 mmol) in dry N,N-Dimethylformamide (1.60 mL, 20.7 mmol) was added N,N-Diisopropylethylamine (0.161 mL, 0.924 mmol) followed by Cyclopropanesulfonyl chloride (0.0354 mL, 0.347 mmol). The reaction mixture was stirred for 2 hours. The reaction mixture was purified by HPLC. 1H NMR (500 MHz, DMSO) δ 8.69 (s, 1H), 8.19 (d, J=8.8, 2H), 7.49 (d, J=8.8, 2H), 6.18 (t, J=5.6, 1H), 4.31 (q, J=15.1, 2H), 3.89 (dd, J=12.2, 9.2, 2H), 3.75-3.52 (m, 5H), 3.44 (d, J=5.0, 2H), 3.19-3.05 (m, 2H), 2.99 (d, J=3.7, 2H), 2.75-2.66 (m, 1H), 1.24 (d, J=6.6, 3H), 1.06 (t, J=7.2, 3H), 0.93 (dt, J=13.8, 5.5, 4H). LC/MS-m/z+501.2 (M+H)+.
Reaction SMILES: [C:1]([CH:3]([CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([C:15]([F:18])([F:17])[F:16])[C:10]=1[CH3:19])[C:4](OC)=O)#[N:2].[OH2:20].[NH2:21][NH2:22]>C(O)C>[NH2:2][C:1]1[NH:22][NH:21][C:4](=[O:20])[C:3]=1[CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([C:15]([F:16])([F:17])[F:18])[C:10]=1[CH3:19]
Reactant: COC(=O)C(C#N)Cc1cccc(C(F)(F)F)c1C
Reactant: NN
Reactant: O
Solvent: CCO
Product: Cc1c(Cc2c(N)[nH][nH]c2=O)cccc1C(F)(F)F
Temperature: 85 °C

Procedure:
A mixture of methyl 2-cyano-3-[2-methyl-3-(trifluoromethyl)phenyl]propanoate (2.2 g, 8.1 mmol) and hydrazine monohydrate (4.1 g, 81 mmol) in ethanol (150 mL) was heated to 85° C. overnight. Reaction mixture was concentrated to dryness. The residue was redissolved with DCM (200 mL) and water (30 mL). Two layers were separated. Organic layers were dried and concentrated to dryness. Desired product was obtained and used in next step. (2.11 g, 96%); LC/MS: MS (ES+) m/e 272 (MH+).
Reaction SMILES: [Br:1][C:2]1[CH:10]=[C:9]([CH3:11])[C:8]([Br:12])=[C:7]2[C:3]=1[CH2:4][CH:5]([CH3:14])[C:6]2=O.[BH4-].[Na+].Cl>C1COCC1.CO>[Br:12][C:8]1[C:9]([CH3:11])=[CH:10][C:2]([Br:1])=[C:3]2[C:7]=1[CH:6]=[C:5]([CH3:14])[CH2:4]2
Reactant: Cc1cc(Br)c2c(c1Br)C(=O)C(C)C2
Agent: Cl
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Solvent: C1CCOC1
Product: CC1=Cc2c(Br)c(C)cc(Br)c2C1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of 16.9 g (52.2 mmol) of 4,7-dibromo-2,6-dimethyl-1-indanone in 300 ml of THF-methanol (2:1, vol.), 3.80 g (100 mmol) of NaBH4 was added in small portions over 1.5 hours at −5° C. (Caution: temperature must be lower 0° C.). The mixture was stirred overnight at ambient temperature. The resulting mixture was acidified with 10% HCl to pH=4. The organic layer was separated; the aqueous layer was extracted with 3×100 ml of methyl-tert-butyl ether. The combined organic fractions were dried over Na2SO4 and evaporated to dryness. To the residue 500 ml of toluene were added. This toluene solution was treated with pTolSO3H (ca. 5 g) for 2 hours at reflux. Then, one more portion (ca. 5 g) of pTolSO3H was added, and the mixture was refluxed for an additional 2 hours. The resulting mixture was cooled to room temperature and passed through a short Silica Gel 60 column (40-63 μm, d 40 mm, 1 100 mm). This column was additionally eluted with 600 ml of hexanes. The combined extract was evaporated to dryness to give a white solid of the title product. Yield 13.6 g (85%).
Reaction SMILES: C([N:8]1[CH2:13][CH2:12][C:11](=O)[CH:10]([C:15]2[CH:20]=[CH:19][C:18]([CH3:21])=[CH:17][CH:16]=2)[CH2:9]1)C1C=CC=CC=1.[CH3:22][C@H:23]1[O:28][C@@H:27]([CH3:29])[CH2:26][NH:25][CH2:24]1.[F:30][C:31]([F:46])([F:45])[C:32]1[CH:33]=[C:34]([CH:38]=[C:39]([C:41]([F:44])([F:43])[F:42])[CH:40]=1)[C:35](Cl)=[O:36]>>[F:30][C:31]([F:46])([F:45])[C:32]1[CH:33]=[C:34]([C:35]([N:8]2[CH2:13][CH2:12][C@H:11]([N:25]3[CH2:26][CH:27]([CH3:29])[O:28][CH:23]([CH3:22])[CH2:24]3)[C@H:10]([C:15]3[CH:16]=[CH:17][C:18]([CH3:21])=[CH:19][CH:20]=3)[CH2:9]2)=[O:36])[CH:38]=[C:39]([C:41]([F:44])([F:43])[F:42])[CH:40]=1
Reactant: O=C(Cl)c1cc(C(F)(F)F)cc(C(F)(F)F)c1
Reactant: C[C@@H]1CNC[C@H](C)O1
Reactant: Cc1ccc(C2CN(Cc3ccccc3)CCC2=O)cc1
Product: Cc1ccc([C@@H]2CN(C(=O)c3cc(C(F)(F)F)cc(C(F)(F)F)c3)CC[C@@H]2N2CC(C)OC(C)C2)cc1

Procedure:
The title compound, MS: m/e=529.3 (M+H+), was prepared in accordance with the general method of example 26 from 1-benzyl-3-(4-methyl-phenyl)-piperidin-4-one, cis-2,6-dimethyl-morpholine and 3,5-bistrifluoromethyl-benzoyl chloride.
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([Cl:8])[N:5]=[C:4]([NH:9][C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([N+:16]([O-:18])=[O:17])[CH:11]=2)[N:3]=1.[CH:19]1([NH2:26])[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]1.[OH-].[Na+].O>CC(C)=O>[Cl:8][C:6]1[N:7]=[C:2]([NH:26][CH:19]2[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]2)[N:3]=[C:4]([NH:9][C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([N+:16]([O-:18])=[O:17])[CH:11]=2)[N:5]=1
Reactant: O=[N+]([O-])c1cccc(Nc2nc(Cl)nc(Cl)n2)c1
Reactant: NC1CCCCCC1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CC(C)=O
Product: O=[N+]([O-])c1cccc(Nc2nc(Cl)nc(NC3CCCCCC3)n2)c1

Procedure:
To 158a (1.0008 g, 3.5 mmol) dissolved in acetone (20 mL) was added a solution of N-cycloheptylamine (0.45 mL, 3.5 mmol) in acetone (5 mL) followed by addition of 2.5 N NaOH (1.4 mL, 3.5 mmol) and water (3.5 mL). The reaction mixture was allowed to stir at reflux for 3 hours under nitrogen. The reaction mixture was extracted 2 times with dichloromethane; the combined organic layers were washed with brine and dried over potassium carbonate. After filtering, the sample was concentrated by rotary evaporation and the resulting solid was dried overnight under vacuum. Flash column chromatography (SiO2, 70:30 hexanes:ethyl acetate) yielded a yellow solid (158b, 991 mg, 78%), mp 82° C.; HPLC: Inertsil ODS-3V C18, 40:10:50 [KH2PO4 (0.01M, pH 3.2): CH3OH: CH3CN], 264 nm, Rt 54.5 min, 99.8% purity; MS (TOF MS ES+): m/z 440 (100), 365 (20.0), 363 (M+H, 53.2).
Reaction SMILES: C1C=C2C=C[O:9][C:4]2=CC=1.C([Li])CCC.[CH3:15][CH2:16][CH2:17][CH2:18][CH2:19][CH3:20].C(#N)C1C=CC=CC=1.Cl.[O:30]1CCCC1>>[C:4]([OH:9])(=[O:30])[C:17]1[CH:16]=[CH:15][CH:20]=[CH:19][CH:18]=1
Reactant: C1CCOC1
Reactant: CCCCCC
Reactant: c1ccc2occc2c1
Agent: Cl
Agent: [Li]CCCC
Solvent: N#Cc1ccccc1
Product: O=C(O)c1ccccc1
Temperature: -78 °C
Reaction time: 3 h

Procedure:
2,3-Benzofuran (0.084 mole) was added to a reaction flask containing 100 milliliters of anhydrous tetrahydrofuran and stirred. The reaction was maintained under an argon atmosphere at -78° C. A 1.6 molar solution of n-butyl lithium in hexane (0.1 mole of n-butyl lithium) was added drop wise to the reaction which was stirred for 3 hours at -78° C. The cooling bath was removed and stirring was continued for 3 hours after the temperature of the reaction mixture reached room temperature. A solution of benzonitrile (0.084 mole, 8.7 grams in 20 milliliters of anhydrous tetrahydrofuran) was added dropwise and the reaction mixture was stirred for 16 hours at room temperature. A 5 weight percent aqueous hydrochloric acid solution (50 milliliters) was added to the reaction flask and the reaction mixture was refluxed for 5 hours. The reaction mixture was cooled to room temperature and the organic layer was separated. The aqueous layer was extracted with three 30 milliliter portions of diethyl ether. The extracts and organic layer were combined and washed with water. Benzoic acid that formed from the hydrolysis of unreacted benzonitrile was removed by washing the organic layer first with a 10 weight percent sodium hydroxide solution then with water. The washed organic layer was dried over anhydrous sodium sulfate. The solvents, diethyl ether, tetrahydrofuran, and hexane, were removed under vacuum to yield an oily product containing 2-benzoylbenzofuran, which was not purified but used directly in the next step.
Reaction SMILES: [Cl:1][C:2]1[CH:14]=[CH:13][C:5]([O:6][C:7]([CH3:12])([CH3:11])[CH2:8][C:9]#[N:10])=[CH:4][CH:3]=1.OO.C(=O)([O-])[O-:18].[K+].[K+].O>CS(C)=O.C(Cl)Cl>[Cl:1][C:2]1[CH:14]=[CH:13][C:5]([O:6][C:7]([CH3:11])([CH3:12])[CH2:8][C:9]([NH2:10])=[O:18])=[CH:4][CH:3]=1
Reactant: CC(C)(CC#N)Oc1ccc(Cl)cc1
Reactant: O=C([O-])[O-]
Agent: OO
Agent: [K+]
Solvent: O
Solvent: CS(C)=O
Solvent: ClCCl
Product: CC(C)(CC(N)=O)Oc1ccc(Cl)cc1
Temperature: 25 °C

Procedure:
A solution of 3-(4-chlorophenoxy)-3-methylbutyronitrile (60.4 mmol) in DMSO (75 mL) is treated with H2O2 (50% w/w) (434 mmol) and potassium carbonate (121 mmol) at zero degrees Celsius. The reaction mixture is stirred at room temperature over the weekend. The reaction mixture is transferred into a separatory funnel using water (100 mL) and CH2Cl2 (200 mL). The mixture is equilibrated and the CH2Cl2 layer is removed. The aqueous layer is extracted two additional times with CH2Cl2 (2×300 mL). The combined CH2Cl2 extracts are washed 5 consecutive times with water (5×200 mL) followed by a brine (500 mL) wash, dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure, which affords 3-(4-chlorophenoxy)-3-methylbutyramide.
Reaction SMILES: [CH2:1]1[C:10]2[C:5](=[C:6]([O:11][CH2:12][C:13]([O:15][CH2:16][CH3:17])=[O:14])[CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][NH:2]1.CCN(CC)CC.[CH3:25][S:26](Cl)(=[O:28])=[O:27]>C(Cl)Cl>[CH3:25][S:26]([N:2]1[CH2:3][CH2:4][C:5]2[C:10](=[CH:9][CH:8]=[CH:7][C:6]=2[O:11][CH2:12][C:13]([O:15][CH2:16][CH3:17])=[O:14])[CH2:1]1)(=[O:28])=[O:27]
Reactant: CS(=O)(=O)Cl
Reactant: CCOC(=O)COc1cccc2c1CCNC2
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CCOC(=O)COc1cccc2c1CCN(S(C)(=O)=O)C2
Temperature: 25 °C
Reaction time: 16 h
Yield: 77.8 %

Procedure:
To a solution of ethyl 2-((1,2,3,4-tetrahydroisoquinolin-5-yl)oxy)acetate (300 mg, 1.28 mmol) and Et3N (387 mg, 3.83 mmol) in DCM (25 mL) cooled in an ice-water bath was added MsCl (176.6 mg, 1.54 mmol) drop wise. The mixture was stirred at 25° C. for 16 h and then quenched with aq. NH4Cl. The mixture was extracted with ethyl acetate and the combined organic layers were concentrated under vacuum to give the crude product (312 mg, 78%) which was used to the next step without purification.
Reaction SMILES: C([N:8]1[CH2:12][CH:11]([C:13]2[CH:18]=[CH:17][C:16]([Cl:19])=[C:15]([Cl:20])[CH:14]=2)[CH:10]([CH:21]([O:23][C:24]2[CH:31]=[CH:30][C:27]([C:28]#[N:29])=[CH:26][N:25]=2)[CH3:22])[CH2:9]1)C1C=CC=CC=1.ClC(OCC(Cl)(Cl)Cl)=O>CC#N>[Cl:20][C:15]1[CH:14]=[C:13]([CH:11]2[CH2:12][NH:8][CH2:9][CH:10]2[CH:21]([O:23][C:24]2[CH:31]=[CH:30][C:27]([C:28]#[N:29])=[CH:26][N:25]=2)[CH3:22])[CH:18]=[CH:17][C:16]=1[Cl:19]
Reactant: CC(Oc1ccc(C#N)cn1)C1CN(Cc2ccccc2)CC1c1ccc(Cl)c(Cl)c1
Agent: O=C(Cl)OCC(Cl)(Cl)Cl
Solvent: CC#N
Product: CC(Oc1ccc(C#N)cn1)C1CNCC1c1ccc(Cl)c(Cl)c1
Reaction time: 4 h
Yield: 58.5 %

Procedure:
To a solution of 6-{(SR)-1-[(3RS,4SR)-1-benzyl-4-(3,4-dichloro-phenyl)-pyrrolidin-3-yl]-ethoxy}-nicotinonitrile 0.75 g (1.70 mmol) dissolved in CH3CN (50 mL) was added 0.56 mL (4.14 mmol) of 2,2,2-trichloroethyl chloroformate and stirring was continued for 4 hours at RT. Volatiles were removed under vacuo, and the crude was dissolved in AcOH (30 mL) before a total of 0.45 g of Zn dust was added portion wise. After three hours at RT, the reaction mixture was filtered on celite, the solvent removed under vacuo, followed by an extraction with EtOAc/aq. NaHCO3 (basic pH). The organic phases were dried on Na2SO4 and column chromatography (SiO2, CH2Cl2/MeOH 9:1) yielded 0.36 g (60%) of the title compound as a colorless oil. ES-MS m/e: 362.3 (M+H+).
Reaction SMILES: C[O:2][C:3](=O)[CH2:4][C:5]1[N:6]([CH2:11][CH3:12])[N:7]=[C:8]([CH3:10])[CH:9]=1.CO.[NH3:16]>>[CH2:11]([N:6]1[C:5]([CH2:4][C:3]([NH2:16])=[O:2])=[CH:9][C:8]([CH3:10])=[N:7]1)[CH3:12]
Reactant: CCn1nc(C)cc1CC(=O)OC
Reactant: N
Solvent: CO
Product: CCn1nc(C)cc1CC(N)=O
Temperature: 25 °C
Reaction time: 20 h

Procedure:
(2-Ethyl-5-methyl-2H-pyrazol-3-yl)-acetic acid methyl ester (4.64 g, 25.46 mmol) was dissolved in 7N ammonia in methanol (100 ml, 700 mmol NH3). The reaction mixture was stirred at rt for 20 h. The solvent was removed under reduced pressure to give 4.25 g (quant. yield) of 2-(2-ethyl-5-methyl-2H-pyrazol-3-yl)-acetamide. LC-MS: tR=0.33 min; [M+H]+=no ionisation.
Reaction SMILES: [Br:1][C:2]1[CH:25]=[CH:24][C:5]([CH2:6][CH2:7][C:8]2[S:9][C:10]3[N:11]=[C:12]([NH2:23])[N:13]=[C:14]([N:17]4[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]4)[C:15]=3[N:16]=2)=[CH:4][CH:3]=1.[CH3:26][O:27][C:28]1[CH:38]=[CH:37][C:31]([O:32][CH2:33][C:34](O)=[O:35])=[CH:30][CH:29]=1>>[NH2:23][C:12]1[N:13]=[C:14]([N:17]2[CH2:18][CH2:19][N:20]([C:34](=[O:35])[CH2:33][O:32][C:31]3[CH:37]=[CH:38][C:28]([O:27][CH3:26])=[CH:29][CH:30]=3)[CH2:21][CH2:22]2)[C:15]2[N:16]=[C:8]([CH2:7][CH2:6][C:5]3[CH:24]=[CH:25][C:2]([Br:1])=[CH:3][CH:4]=3)[S:9][C:10]=2[N:11]=1
Reactant: COc1ccc(OCC(=O)O)cc1
Reactant: Nc1nc(N2CCNCC2)c2nc(CCc3ccc(Br)cc3)sc2n1
Product: COc1ccc(OCC(=O)N2CCN(c3nc(N)nc4sc(CCc5ccc(Br)cc5)nc34)CC2)cc1
Yield: 40 %

Procedure:
This compound was prepared from 2-(4-bromophenethyl)-7-(piperazin-1-yl)thiazolo[5,4-d]pyrimidin-5-amine using 4-methoxyphenoxyacetic acid in a yield of 40%, according to the procedure for the synthesis of example 50.
Reaction SMILES: [Cl:1][Si:2]([CH3:10])([CH3:9])[CH:3]=[CH:4][Si:5]([Cl:8])([CH3:7])[CH3:6].Cl[CH:12](Cl)[SiH](C)C=C([SiH](C)C(Cl)Cl)C>>[Cl:1][Si:2]([CH3:10])([CH3:9])[CH2:3][CH:4]([Si:5]([Cl:8])([CH3:7])[CH3:6])[CH3:12]
Reactant: CC(=C[SiH](C)C(Cl)Cl)[SiH](C)C(Cl)Cl
Reactant: C[Si](C)(Cl)C=C[Si](C)(C)Cl
Product: CC(C[Si](C)(C)Cl)[Si](C)(C)Cl

Procedure:
Example 1 was repeated with the modification that, instead of 300.0 (1.41 mol) of 1,2-bis(chlorodimethylsilyl)ethene, 300.0 g (1.32 mol) of 1,2-bis(dichlorodimethylsilyl)prop-1-ene were used. The results are summarized in Table 1.
Reaction SMILES: [P:1]([O:5][CH2:6][C@H:7]1[O:11][C@@H:10]([N:12]2[CH:19]=[C:18]([NH2:20])[C:16](=[O:17])[NH:15][C:13]2=[O:14])[CH2:9][C@@H:8]1[OH:21])([OH:4])([OH:3])=[O:2].[N:22]([O-])=O.[Na+]>>[P:1]([O:5][CH2:6][C@H:7]1[O:11][C@@H:10]([N:12]2[CH2:19][C:18](=[N+:20]=[N-:22])[C:16](=[O:17])[NH:15][C:13]2=[O:14])[CH2:9][C@@H:8]1[OH:21])([OH:3])([OH:4])=[O:2]
Reactant: O=N[O-]
Reactant: Nc1cn([C@H]2C[C@H](O)[C@@H](COP(=O)(O)O)O2)c(=O)[nH]c1=O
Agent: [Na+]
Product: [N-]=[N+]=C1CN([C@H]2C[C@H](O)[C@@H](COP(=O)(O)O)O2)C(=O)NC1=O

Procedure:
acidifying said 5-amino-2'-deoxyuridine-5'-monophosphate and reacting the acidified product with sodium nitrite to produce 5-diazo-2'-deoxyuridine-5'-monophosphate;
Reaction SMILES: [N:1]1[C:10]2[C:5](=[C:6]([C:11]([C:13]3[N:14]=[CH:15][N:16](C(C4C=CC=CC=4)(C4C=CC=CC=4)C4C=CC=CC=4)[CH:17]=3)=[O:12])[CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.[OH-].[Na+]>C(O)(=O)C.O>[NH:16]1[CH:17]=[C:13]([C:11]([C:6]2[CH:7]=[CH:8][CH:9]=[C:10]3[C:5]=2[CH:4]=[CH:3][CH:2]=[N:1]3)=[O:12])[N:14]=[CH:15]1
Reactant: O=C(c1cn(C(c2ccccc2)(c2ccccc2)c2ccccc2)cn1)c1cccc2ncccc12
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CC(=O)O
Product: O=C(c1c[nH]cn1)c1cccc2ncccc12

Procedure:
Quinolin-5-yl-(1-trityl-1H-imidazol-4-yl)-methanone (Intermediate G1) in acetic acid:water (˜2:1) was heated to 100° C. for 1 h. The mixture was basified with 1 M NaOH and extracted (6×) with CHCl3:iPrOH (3:1). The organic solution was dried over MgSO4, filtered, and concentrated onto silica gel. The material was eluted from a column of silica with 5% NH3-MeOH:CH2Cl2 to give (1H-imidazol-4-yl)-quinolin-5-yl-methanone (Intermediate G2).
Reaction SMILES: [F:1][C:2]([F:47])([F:46])[C:3]([C:27]1[N:31](COCC[Si](C)(C)C)[C:30]2[CH:40]=[CH:41][C:42]([C:44]#[N:45])=[CH:43][C:29]=2[N:28]=1)(O)[C:4]1[C:12]([S:13][CH3:14])=[CH:11][C:10]([CH3:15])=[C:9]2[C:5]=1[CH:6]=[CH:7][N:8]2[S:16]([C:19]1[CH:25]=[CH:24][C:22]([CH3:23])=[CH:21][CH:20]=1)(=[O:18])=[O:17].FC(F)(F)C(C1N(COCC[Si](C)(C)C)C2C=C(C#N)C=CC=2N=1)(O)C1C(SC)=CC(C)=C2C=1C=C[N:55]2S(C1C=CC(C)=CC=1)(=O)=O.Cl.S(Cl)(Cl)=O.C(O)C>CN(C=O)C.N>[NH2:55][C:3]([C:27]1[NH:31][C:30]2[CH:40]=[CH:41][C:42]([C:44]#[N:45])=[CH:43][C:29]=2[N:28]=1)([C:4]1[C:12]([S:13][CH3:14])=[CH:11][C:10]([CH3:15])=[C:9]2[C:5]=1[CH:6]=[CH:7][N:8]2[S:16]([C:19]1[CH:20]=[CH:21][C:22]([CH3:23])=[CH:24][CH:25]=1)(=[O:17])=[O:18])[C:2]([F:47])([F:46])[F:1]
Reactant: CSc1cc(C)c2c(ccn2S(=O)(=O)c2ccc(C)cc2)c1C(O)(c1nc2cc(C#N)ccc2n1COCC[Si](C)(C)C)C(F)(F)F
Reactant: CSc1cc(C)c2c(ccn2S(=O)(=O)c2ccc(C)cc2)c1C(O)(c1nc2ccc(C#N)cc2n1COCC[Si](C)(C)C)C(F)(F)F
Agent: Cl
Agent: N
Solvent: O=S(Cl)Cl
Solvent: CN(C)C=O
Solvent: CCO
Product: CSc1cc(C)c2c(ccn2S(=O)(=O)c2ccc(C)cc2)c1C(N)(c1nc2cc(C#N)ccc2[nH]1)C(F)(F)F
Temperature: 60 °C

Procedure:
To a mixture of (±)-2-(2,2,2-trifluoro-1-hydroxy-1-(7-methyl-5-(methylthio)-1-tosyl-1H-indol-4-yl)ethyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-benzo[d]imidazole-5-carbonitrile and (±)-2-(2,2,2-trifluoro-1-hydroxy-1-(7-methyl-5-(methylthio)-1-tosyl-1H-indol-4-yl)ethyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-benzo[d]imidazole-6-carbonitrile (Example 14-A) (425 mg, 0.6 mmol) was added HCl (1.25M in MeOH, 4.85 mL, 6.06 mmol) and the mixture was stirred at 60° C. After 40 minutes the mixture was cooled to room temperature and concentrated. The mixture was dissolved in CHCl3 (12 mL), then was added thionyl chloride (0.44 mL, 6.06 mmol) and one drop of DMF and the mixture was heated at 70° C. After 4 hours the reaction was cooled to room temperature and stirred at room temperature overnight. The reaction was then concentrated, dissolved in ammonia in ethanol (2.0M, 30.3 mL, 60.6 mmol) and stirred at room temperature. After 15 minutes the reaction was concentrated and purified directly by flash chromatography (0-70% EtOAc in heptanes). MS (ESI+) m/z 570.3 (M+H).
Reaction SMILES: [C:1]([OH:4])(=[S:3])[CH3:2].C(=O)([O-])[O-].[K+].[K+].Br[CH:12]([CH3:30])[C:13]([NH:15][C:16]1[CH:21]=[CH:20][C:19]([C:22]2[CH:23]([CH3:29])[CH2:24][C:25](=[O:28])[NH:26][N:27]=2)=[CH:18][CH:17]=1)=[O:14].[K+].[Br-]>O.CN(C)C=O>[C:1]([S:3][CH:12]([CH3:30])[C:13]([NH:15][C:16]1[CH:17]=[CH:18][C:19]([C:22]2[CH:23]([CH3:29])[CH2:24][C:25](=[O:28])[NH:26][N:27]=2)=[CH:20][CH:21]=1)=[O:14])(=[O:4])[CH3:2]
Reactant: CC(Br)C(=O)Nc1ccc(C2=NNC(=O)CC2C)cc1
Reactant: CC(O)=S
Agent: O=C([O-])[O-]
Agent: [Br-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: CC(=O)SC(C)C(=O)Nc1ccc(C2=NNC(=O)CC2C)cc1

Procedure:
To 20 ml of N,N-dimethylformamide were added 0.54 g of thioacetic acid, 0.98 g of anhydrous potassium carbonate and then 2.0 g of 6-[4-(α-bromopropionylamino)-phenyl]-5-methyl-4,5-dihydro-3(2H)-pyridazinone, and the mixture was reacted for 2 hours at room temperature. The mixture was further reacted for 1 hour after the addition of 2 ml of water. Insoluble matters were removed from the mixture by filtration and the filtrate was concentrated under reduced pressure to obtain a crude end product which was then purified by column chromatography on silica gel (solvent: benzene, acetic acid and methanol in a ratio of 10:3:0.6) whereby 1.8 g of the purified end product was obtained. Amorphous powder. IR-absorption spectra (KBr tablets, cm-1): 3275, 1680, 1540, 1350, 1040 and 840.
Reaction SMILES: [CH3:1][N:2]([CH:7]([CH:14]1[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]1)[CH:8]1[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]1)[CH2:3][C:4](O)=O.C(OC(=O)C)(=[O:22])C.[CH:27]([OH:29])=[O:28]>>[CH3:4][CH:3]([C:27]([OH:29])=[O:28])[N:2]([CH:7]([CH:14]1[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]1)[CH:8]1[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]1)[CH:1]=[O:22]
Reactant: CN(CC(=O)O)C(C1CCCCC1)C1CCCCC1
Reactant: CC(=O)OC(C)=O
Reactant: O=CO
Product: CC(C(=O)O)N(C=O)C(C1CCCCC1)C1CCCCC1
Temperature: 5 °C
Reaction time: 48 h

Procedure:
143 Parts of methyl N-[(dicyclohexyl)methyl]glycine were added dropwise to 290 parts of formic acid while cooling to 5° C. Subsequently 90 parts of acetic anhydride were added, and the mixture was kept at room temperature for 48 hours. Destillation under vacuo afforded 154 parts of methyl N-[(dicyclohexyl)methyl]-N-formylglycine (int. 2).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH3:8])[C:3]=1[C:9]([O:11][CH2:12][CH3:13])=[O:10].[Br:14]N1C(=O)CCC1=O>>[Br:14][CH2:8][C:4]1[C:3]([C:9]([O:11][CH2:12][CH3:13])=[O:10])=[C:2]([Cl:1])[CH:7]=[CH:6][CH:5]=1
Reactant: CCOC(=O)c1c(C)cccc1Cl
Reactant: O=C1CCC(=O)N1Br
Product: CCOC(=O)c1c(Cl)cccc1CBr

Procedure:
Reaction of ethyl 3-chloro-o-toluate with N-bromosuccinimide as described in Example 1a provides ethyl α-bromo-3-chloro-o-toluate as an oil.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[N:8]([O-])=O.[Na+].[CH2:12]([S:16][C:17]1[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[C:20]([OH:27])=[CH:19][CH:18]=1)[CH2:13][CH2:14][CH3:15]>>[C:2]1([N:1]=[N:8][C:19]2[CH:18]=[C:17]([S:16][CH2:12][CH2:13][CH2:14][CH3:15])[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[C:20]=2[OH:27])[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: Nc1ccccc1
Reactant: O=N[O-]
Reactant: CCCCSc1ccc(O)c2ccccc12
Agent: [Na+]
Product: CCCCSc1cc(N=Nc2ccccc2)c(O)c2ccccc12

Procedure:
This is prepared similarly to Example 1 using 0.8 g (8.6 mmoles) of aniline, 0.65 g (9.5 mmoles) of sodium nitrite, and 2 g (8.6 mmoles) of 4-butylthio-1-naphthol.