Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][SiH2:2][Cl:3].[CH2:4]=[CH:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH3:15]>C(O)(C)C.O.Cl.Cl.Cl[Pt](Cl)(Cl)Cl>[Cl:1][Si:2]([Cl:3])([CH2:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][CH2:6][CH2:5][CH3:4])[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH3:15]
Reactant: C=CCCCCCCCCCC
Reactant: Cl[SiH2]Cl
Agent: Cl[Pt](Cl)(Cl)Cl
Agent: Cl
Solvent: O
Solvent: CC(C)O
Product: CCCCCCCCCCCC[Si](Cl)(Cl)CCCCCCCCCCCC
Temperature: 0 °C
Reaction time: 40 h

Procedure:
To a dry tarred 500 mL Schlenk bomb flask was condensed 29.0 g (0.286 mol) of dichlorosilane at −78° C. To this was added 100 g (0.594 mol) of 1-dodecene under an argon flow. This mixture was allowed to warm to 0° C., then 100 mg (0.193 mmol) of hexachloroplatinic acid hexahydrate dissolved in 2 mL of isopropanol was added via syringe. The mixture was allowed to slowly warm to room temperature where it was allowed to stir for 40 hours. After this time the solution was cannula transferred into a dry 250 mL 3-necked round bottom flask equipped with a fractional distillation apparatus. The mixture was distilled at 220° C. at 0.1 mmHg. Yield: 78.1 g (62.5%). 1H NMR (400 MHz, C6D6): δ=1.6-1.4 (m, 4H), 1.4-1.1 (m, 36H), 1.0-0.8 (m, 10H). 13C NMR (100 MHz, C6D6): δ=33.19, 32.72, 30.51, 30.30, 30.21, 29.89, 23.51, 23.16, 20.92, 14.77. HRMS (EI) m/z, calcd for C24H50Cl2Si (M+): 436.3059; found: 436.3058.
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([NH:8][C@H:9]([C:11]2[N:20]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[C:19](=[O:27])[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][C:17]=3Cl)[N:12]=2)[CH3:10])[C:5]([C:29]#[N:30])=[CH:4][N:3]=1.C([Sn](CCCC)(CCCC)[C:36]1[CH:41]=[CH:40][N:39]=[N:38][CH:37]=1)CCC.O>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[NH2:1][C:2]1[N:7]=[C:6]([NH:8][C@H:9]([C:11]2[N:20]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[C:19](=[O:27])[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][C:17]=3[C:36]3[CH:41]=[CH:40][N:39]=[N:38][CH:37]=3)[N:12]=2)[CH3:10])[C:5]([C:29]#[N:30])=[CH:4][N:3]=1
Reactant: C[C@H](Nc1nc(N)ncc1C#N)c1nc2cccc(Cl)c2c(=O)n1-c1ccccc1
Reactant: CCCC[Sn](CCCC)(CCCC)c1ccnnc1
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: c1ccc(P(c2ccccc2)[c-]2cccc2)cc1
Solvent: O
Solvent: C1COCCO1
Product: C[C@H](Nc1nc(N)ncc1C#N)c1nc2cccc(-c3ccnnc3)c2c(=O)n1-c1ccccc1
Temperature: 25 °C

Procedure:
A mixture of (S)-2-amino-4-(1-(5-chloro-4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)ethylamino)pyrimidine-5-carbonitrile 59 (50 mg, 0.12 mmol), 4-(tributylstannyl)pyridazine (89 mg, 0.24 mmol) and PdCl2(dppf) (9.7 mg, 0.012 mmol) in 1,4-dioxane (5 mL) was stirred at reflux under argon for 16 h. The mixture was allowed to cool to RT, poured into water (20 mL) and extracted with ethyl acetate (2×15 mL). The combined organic layers were washed with brine, dried over Na2SO4 and filtered. The filtrate was concentrated in vacuo and the residue was purified by flash column chromatography on silica gel eluting with 3% MeOH-DCM to afford the product, (S)-2-amino-4-((1-(4-oxo-3-phenyl-5-(pyridazin-4-yl)-3,4-dihydroquinazolin-2-yl)ethyl)amino)pyrimidine-5-carbonitrile 66. ESI-MS m/z: 462.2 [M+H]+.
Reaction SMILES: [F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1[C:9]1([O:20][CH3:21])[CH2:12][N:11](C(OC(C)(C)C)=O)[CH2:10]1.FC(F)(F)C(O)=O>ClCCl>[F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1[C:9]1([O:20][CH3:21])[CH2:12][NH:11][CH2:10]1
Reactant: COC1(c2cccc(F)c2F)CN(C(=O)OC(C)(C)C)C1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: COC1(c2cccc(F)c2F)CNC1
Temperature: 25 °C
Reaction time: 2 h
Yield: 34.3 %

Procedure:
To a stirred solution of tert-butyl 3-(2,3-difluorophenyl)-3-methoxyazetidine-1-carboxylate (0.7 g, 2.34 mmol) in dichloromethane (20 mL) was added trifluoroacetic acid (3 ml, 40 mmol). The resulting mixture was stirred at ambient temperature for 2 h. The solvent was evaporated and the crude product was purified on a Biotage Isolute SCX-3 SPE column (washed with methanol and eluted with methanol/triethylamine, 4:1). The solvents where evaporated to give (0.16 g, 64%) of the title compound. The amine was converted to the oxalic acid salt and recrystallized from ethanol/diethyl ether/diisopropyl ether: M.p. 141-142° C. MS m/z (relative intensity, 70 eV) 199 (M+, 1), 170 (bp), 169 (97), 140 (82), 127 (47).
Reaction SMILES: [OH:1][C:2]1[C:3]([CH3:16])=[C:4]([C:8]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=O)[CH:5]=[CH:6][CH:7]=1.C([SiH](CC)CC)C.C(O)(C(F)(F)F)=O.[NH4+].[Cl-]>C(Cl)Cl>[CH2:8]([C:4]1[C:3]([CH3:16])=[C:2]([OH:1])[CH:7]=[CH:6][CH:5]=1)[C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1
Reactant: Cc1c(O)cccc1C(=O)c1ccccc1
Agent: CC[SiH](CC)CC
Agent: [Cl-]
Agent: [NH4+]
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: Cc1c(O)cccc1Cc1ccccc1
Temperature: 0 °C
Reaction time: 72 h
Yield: 80 %

Procedure:
A solution of (3-hydroxy-2-methylphenyl)(phenyl)methanone prepared as in Step 2 (1.60 g, 7.54 mmole) in anhydrous CH2Cl2 (70 mL) was cooled to 0° C. Triethylsilane (32.5 mL, 203 mmole) and TFA (52.3 mL, 679 mmole) were added in portions at 0° C. over a period of 3 days with the mixture brought back to reflux after each addition. After 3 days, the mixture was cooled, poured into sat. NH4Cl (200 mL) and extracted with CH2Cl2 (3×200 mL). The combined extracts were washed with H2O (200 mL), brine (100 mL), dried over MgSO4, filtered and concentrated in vacuo to give a yellow oil. The crude product was purified by silica chromatography (95:5 hexanes:EtOAc) to give 1.19 g (80% yield) of the product as a pale yellow oil: EIHRMS m/z 198.1072 (M+, C14H14O, Calc'd 198.1045).
Reaction SMILES: [OH:1][C:2]1[C:7]([OH:8])=[CH:6][N:5]=[C:4]([C:9]([O:11][CH3:12])=[O:10])[CH:3]=1.C([O-])([O-])=O.[K+].[K+].Br[CH2:20][CH2:21]Br>CN(C=O)C>[O:1]1[C:2]2[CH:3]=[C:4]([C:9]([O:11][CH3:12])=[O:10])[N:5]=[CH:6][C:7]=2[O:8][CH2:21][CH2:20]1
Reactant: COC(=O)c1cc(O)c(O)cn1
Reactant: BrCCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: COC(=O)c1cc2c(cn1)OCCO2
Temperature: 115 °C
Yield: 86.6 %

Procedure:
To a stirred solution of methyl 4,5-dihydroxypyridine-2-carboxylate (348 mg, 2.06 mmol) in DMF (20 mL) is added solid K2CO3 (3.1 g, 22 mmol) and 1,2-dibromoethane (386 μL, 4.5 mmol). The mixture is heated at 115° C. for 2 h. DMF is removed in vacuo, the residue is partitioned between water and EtOAc. The aqueous layer is again extracted with EtOAc. The combined organic layers are dried (MgSO4) and concentrated in vacuo to give a yellow solid for methyl 2,3-dihydro-1,4-dioxino[2,3-c]pyridine-7-carboxylate (348 mg, 86%): 1H NMR (400 MHz, CDCl3) δ 8.29, 7.71, 4.39, 3.99.
Reaction SMILES: [CH3:1][N:2]([CH3:12])[CH:3](OC(C)(C)C)N(C)C.[C:13]([O:18][CH2:19][CH3:20])(=[O:17])[CH2:14][CH2:15][CH3:16]>>[CH3:1][N:2](/[CH:12]=[C:14](\[CH2:15][CH3:16])/[C:13]([O:18][CH2:19][CH3:20])=[O:17])[CH3:3]
Reactant: CN(C)C(OC(C)(C)C)N(C)C
Reactant: CCCC(=O)OCC
Product: CCOC(=O)/C(=C/N(C)C)CC

Procedure:
The title compound was prepared from N,N,N′,N′-tetramethyl-1-[(2-methylpropan-2-yl)oxy]methanediamine and ethyl butanoate according to the procedure for the preparation of Example 84, part A. [M+H] Calc'd for C9H17NO2, 172. Found, 172.
Reaction SMILES: Cl.[NH2:2][C:3]1[C:18]([Cl:19])=[CH:17][C:6]([C:7]([NH:9][CH2:10][CH2:11][N:12]([CH2:15][CH3:16])[CH2:13][CH3:14])=[O:8])=[C:5]([OH:20])[CH:4]=1.C(=O)([O-])[O-].[K+].[K+].[I-].[Na+].Cl[CH:30]([CH3:34])[C:31](=[O:33])[CH3:32]>CN(C=O)C>[ClH:19].[NH2:2][C:3]1[C:18]([Cl:19])=[CH:17][C:6]([C:7]([NH:9][CH2:10][CH2:11][N:12]([CH2:13][CH3:14])[CH2:15][CH3:16])=[O:8])=[C:5]([O:20][CH:30]([CH3:34])[C:31](=[O:33])[CH3:32])[CH:4]=1
Reactant: CC(=O)C(C)Cl
Reactant: CCN(CC)CCNC(=O)c1cc(Cl)c(N)cc1O
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [I-]
Solvent: CN(C)C=O
Product: CCN(CC)CCNC(=O)c1cc(Cl)c(N)cc1OC(C)C(C)=O
Yield: 161.4 %

Procedure:
To a stirred suspension of 4-amino-5-chloro-N-[2-(diethylamino)ethyl]-2-hydroxybenzamide hydrochloride (19.4 g, 60 mmoles), potassium carbonate (41.6 g, 0.3 moles) and sodium iodide (10 g) in DMF (100 ml) was added 3-chloro-2-butanone (9.5 g, 89 mmoles) and the mixture vigorously stirred and heated to 70°-80° for 2 hours followed by cooling and partition between water and methylene chloride. The organic phase was washed with water, dried and concentrated. The residue was treated with 2N HCl and azeotroped with n-propanol, and crystallized from acetone to give 19.0 g (81%) of the title compound mp 177°-179°.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([CH2:15][C:16](O)=O)=[N:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:19][C:20]1[CH:21]=[C:22]([CH:25]=[CH:26][C:27]=1[NH:28][CH2:29][CH:30]1[CH2:32][CH2:31]1)[C:23]#[N:24].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CC(O)=O>[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([CH2:15][C:16]2[N:28]([CH2:29][CH:30]3[CH2:32][CH2:31]3)[C:27]3[CH:26]=[CH:25][C:22]([C:23]#[N:24])=[CH:21][C:20]=3[N:19]=2)=[N:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C(O)Cc1ccc(OCc2ccccc2)cn1
Reactant: N#Cc1ccc(NCC2CC2)c(N)c1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CC(=O)O
Product: N#Cc1ccc2c(c1)nc(Cc1ccc(OCc3ccccc3)cn1)n2CC1CC1

Procedure:
Following the general procedure 13B, 360 mg (1.48 mmol) of [5-(benzyloxy)-2-pyridinyl]acetic acid was coupled with 3-amino-4-[(Cyclopropylmethyl)amino]benzonitrile using HATU. The resulting intermediate was heated in HOAc (20 mL) at 90° C. overnight. After being concentrated, the crude residue was purified by silica gel column chromatography to afford the pure product (230 mg, 40% for 2 steps) as an oil. MS (ESI) (M+H)+=395.
Reaction SMILES: C(O[C:4]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH2:7][CH:6]([CH3:14])[N:5]=1)C.Cl.[NH2:16][NH2:17]>>[NH:16]([C:4]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH2:7][CH:6]([CH3:14])[N:5]=1)[NH2:17]
Reactant: NN
Reactant: CCOC1=NC(C)Cc2ccccc21
Agent: Cl
Product: CC1Cc2ccccc2C(NN)=N1

Procedure:
In a manner similar to that of Step B of Example 1, condensation of 1-ethoxy-3-methyl-3,4-dihydroisoquinoline (1.0 g.) and hydrazine monohydrochloride (0.36 g.) and three recrystallizations of the resulting product from ethanol-ether afforded 1-hydrazino-3-methyl-3,4-dihydroisoquinoline (V: Y=CH3, Y'= Z=Z'=H) hydrochloride (m.p. 174°-176° C.).
Reaction SMILES: [Br:1][C:2]1[S:6][C:5]([C:7]2[CH:15]=[CH:14][C:10]([C:11]([OH:13])=O)=[CH:9][CH:8]=2)=[CH:4][CH:3]=1.[NH:16]1[CH2:20][CH2:19][CH2:18][C@H:17]1[CH2:21][N:22]1[CH2:26][CH2:25][CH2:24][CH2:23]1>>[Br:1][C:2]1[S:6][C:5]([C:7]2[CH:8]=[CH:9][C:10]([C:11]([N:16]3[CH2:20][CH2:19][CH2:18][C@H:17]3[CH2:21][N:22]3[CH2:26][CH2:25][CH2:24][CH2:23]3)=[O:13])=[CH:14][CH:15]=2)=[CH:4][CH:3]=1
Reactant: O=C(O)c1ccc(-c2ccc(Br)s2)cc1
Reactant: C1CN[C@H](CN2CCCC2)C1
Product: O=C(c1ccc(-c2ccc(Br)s2)cc1)N1CCC[C@H]1CN1CCCC1

Procedure:
The title compound is prepared in a manner substantially analogous to General Procedure D using 4-(5-Bromo-thiophen-2-yl)-benzoic acid (CAS 1545208-54-4) and (S)(+)-1-(2-pyrrolidinylmethyl)pyrrolidine to give the title compound (5.42 g). MS (ES+) 419.0 (M+H)+
Reaction SMILES: [C:1]([CH:3]([C:11]1[C:16]([C:17]([F:20])([F:19])[F:18])=[CH:15][C:14]([N+:21]([O-:23])=[O:22])=[CH:13][N:12]=1)C(OC(C)(C)C)=O)#[N:2].Cl>CO>[N+:21]([C:14]1[CH:15]=[C:16]([C:17]([F:20])([F:18])[F:19])[C:11]([CH2:3][C:1]#[N:2])=[N:12][CH:13]=1)([O-:23])=[O:22]
Reactant: CC(C)(C)OC(=O)C(C#N)c1ncc([N+](=O)[O-])cc1C(F)(F)F
Agent: Cl
Solvent: CO
Product: N#CCc1ncc([N+](=O)[O-])cc1C(F)(F)F
Reaction time: 10 h
Yield: 54.3 %

Procedure:
To a solution of tert-butyl 2-cyano-2-(5-nitro-3-(trifluoromethyl)pyridin-2-yl)acetate (1.06 g, 3.20 mmol) in MeOH (80 mL) was added HCl (20 mL, 3.20 mmol). The mixture was at 70° C. for 10 h. Then the solution was concentrated and distributed between EA and saturated NaHCO3 solution. The combined organic extract was washed with brine, dried over MgSO4, filtered and concentrated. The resulting 2-(5-nitro-3-(trifluoromethyl)pyridin-2-yl)acetonitrile (402 mg, 1.739 mmol, 54.4% yield) was used in the next step without further purification. TLC (PE/EA=5:1, Rf=0.6): 1H NMR (400 MHz, CDCl3) δ 9.56 (d, J=2.21 Hz, 1H), 8.63-8.87 (m, 1H), 4.20 (br. s., 2H); ES-LCMS m/z 232.0 (M+H).
Reaction SMILES: [H-].[Na+].[CH3:3][O:4][C:5]1[C:6]([NH2:11])=[N:7][CH:8]=[CH:9][N:10]=1.[Cl:12][C:13]1[C:18]([Cl:19])=[C:17]([F:20])[CH:16]=[CH:15][C:14]=1[S:21](Cl)(=[O:23])=[O:22]>CN1CCCC1=O>[Cl:12][C:13]1[C:18]([Cl:19])=[C:17]([F:20])[CH:16]=[CH:15][C:14]=1[S:21]([NH:11][C:6]1[C:5]([O:4][CH3:3])=[N:10][CH:9]=[CH:8][N:7]=1)(=[O:23])=[O:22]
Reactant: O=S(=O)(Cl)c1ccc(F)c(Cl)c1Cl
Reactant: COc1nccnc1N
Agent: [H-]
Agent: [Na+]
Solvent: CN1CCCC1=O
Product: COc1nccnc1NS(=O)(=O)c1ccc(F)c(Cl)c1Cl
Reaction time: 0.5 h

Procedure:
Sodium hydride (0.4 g of a 60% dispersion in oil) was added to a solution of 3-methoxy-2-pyrazinamine (0.25 g) in N-methylpyrrolidinone (10 mL). After 0.5 h, 2,3-dichloro-4-fluorobenzenesulphonyl chloride (Example 185a) (0.63 g) was added. After 16 h at room temperature the reaction mixture was quenched with 2M aqueous HCl, extracted with ethyl acetate, dried (MgSO4) and evaporated. Purification was by silica gel chromatography eluting with ethyl acetate/iso-hexane mixtures. Yield 0.16 g.
Reaction SMILES: [CH3:1][O:2][CH2:3][O:4][C:5]1[CH:12]=[CH:11][C:8]([CH:9]=[O:10])=[CH:7][CH:6]=1.[OH:13][CH2:14][C:15]([CH3:19])([CH2:17]O)[CH3:16].C1(C)C=CC(S([O-])(=O)=O)=CC=1.[NH+]1C=CC=CC=1.C1C=CC=CC=1>O>[CH3:1][O:2][CH2:3][O:4][C:5]1[CH:12]=[CH:11][C:8]([CH:9]2[O:13][CH2:14][C:15]([CH3:19])([CH3:17])[CH2:16][O:10]2)=[CH:7][CH:6]=1
Reactant: CC(C)(CO)CO
Reactant: COCOc1ccc(C=O)cc1
Agent: Cc1ccc(S(=O)(=O)[O-])cc1
Agent: c1cc[nH+]cc1
Solvent: c1ccccc1
Solvent: O
Product: COCOc1ccc(C2OCC(C)(C)CO2)cc1

Procedure:
A solution of 4-methoxymethoxybenzaldehyde, neopentyl glycol (10.3 g, 98.9 mmol), pyridinium para-toluenesulfonate (1.0 g, 3.98 mmol), and benzene (500 ml) was refluxed with azeotropic removal of water for several hours, under argon. The cooled reaction mixture was quenched with 2 ml of triethylamine, and concentrated on rotary evaporator. The product was chromatographed (silica gel, 5% ethyl acetate in hexanes), yielding about 14.83 g of the product.
Reaction SMILES: CC(C)([O-])C.[K+].[N+:7]([C:10]1[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[CH:12][CH:11]=1)([O-:9])=[O:8].ClC1C=CC(O[CH2:24][C:25]#[N:26])=CC=1.Cl>CN(C=O)C>[CH3:17][O:16][C:13]1[CH:14]=[CH:15][C:10]([N+:7]([O-:9])=[O:8])=[C:11]([CH2:24][C:25]#[N:26])[CH:12]=1
Reactant: COc1ccc([N+](=O)[O-])cc1
Reactant: N#CCOc1ccc(Cl)cc1
Agent: CC(C)(C)[O-]
Agent: Cl
Agent: [K+]
Solvent: CN(C)C=O
Product: COc1ccc([N+](=O)[O-])c(CC#N)c1
Temperature: -10 °C
Reaction time: 0.5 h
Yield: 39.3 %

Procedure:
24.0 g (214 mmol) potassium-tert-butoxide in 100 mL DMF were slowly added dropwise to a solution of 13.17 g (86.0 mmol) 4-nitroanisole and 18.0 g (107 mmol) 4-chlorophenoxyacetonitrile in 50 mL DMF. The reaction mixture was stirred for 30 min at −10° C. and then poured into 300 g of a 1:1 mixture of conc. HCl and ice. After extraction with EtOAc the organic phase was washed with water, dried and concentrated to dryness by rotary evaporation in vacuo with gentle heating. The residue was treated with a 1:1 mixture of PE/EtOAc and the product that crystallised out was suction filtered. After washing with a 1:1 mixture of PE/EtOAc the crystals were dried in the air. 6.5 g of the desired product was obtained.
Reaction SMILES: [Br:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][NH2:7])=[CH:4][CH:3]=1.[OH-].[Na+].Cl[C:13]([O:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[O:14].CCOC(C)=O>C1COCC1.O.[Cl-].[Na+].O>[CH2:16]([O:15][C:13](=[O:14])[NH:7][CH2:6][C:5]1[CH:8]=[CH:9][C:2]([Br:1])=[CH:3][CH:4]=1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1
Reactant: O=C(Cl)OCc1ccccc1
Reactant: NCc1ccc(Br)cc1
Agent: [Cl-]
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Solvent: CCOC(C)=O
Product: O=C(NCc1ccc(Br)cc1)OCc1ccccc1
Temperature: 0 °C
Reaction time: 18 h
Yield: 107.6 %

Procedure:
A solution of 4-bromobenzylamine (5 g, 26.9 mmol) in THF (50 ml) and water (50 ml) was cooled down to 0° C. with sodium hydroxide (1.13 g, 28.2 mmol). Benzyl chloroformate (4.0 ml, 28.2 mmol) was added slowly and the reaction mixture was stirred at 0° C. for 1 h and at r.t. for 18 hours. Brine (50 ml) and EtOAc (50 mL) were added and the phases were separated. The aqueous phase was extracted with EtOAc (40 mL). The organic phase was dried over magnesium sulfate, filtered and concentrated to dryness to yield a light pink solid (9.27 g, 100%). 1H NMR (300 MHz, CDCl3), δ: 4.34 (2 H, d, J=6.0 Hz, CH2NH), 5.14 (2 H, s, OCH2), 7.17 (2 H, d, J=8.1 Hz, Ar), 7.33-7.40 (5 H, m, Ar), 7.46 (2 H, d, J=8.3 Hz, Ar)
Reaction SMILES: [H-].[Al+3].[Li+].[H-].[H-].[H-].[C:7]1([CH3:14])[C:8](C)=[CH:9][CH:10]=[CH:11][CH:12]=1.C([O:17][CH2:18]C)C.CCCCCC.C1(C)C=CC=CC=1.C[CH2:34][O:35]CC>O1CCCC1>[C:7]1([CH:14]([CH2:18][OH:17])[CH2:34][OH:35])[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1
Reactant: CCOCC
Reactant: Cc1ccccc1C
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Solvent: CCCCCC
Solvent: Cc1ccccc1
Product: OCC(CO)c1ccccc1
Temperature: 0 °C
Yield: 72 %

Procedure:
The reaction is carried out in a nitrogen atmosphere in a predried 250 ml RB flask with a side arm and a distillation apparatus leading to a nitrogen outlet. 180 mmoles of lithium aluminum hydride is added to the flask in sufficient tetrahydrofuran to dissolve the lithium aluminum hydride. The solution is cooled with rapid stirring to about 0° C. and 30 mmoles of diethyl phenylmalonic acid ester is slowly added followed by four ml of dry xylene which functions as a heat transfer material and prevents the contents of the flask from "bumping". The solution is heated to about 135° C. and maintained at such temperature for approximately two hours. The reaction mixture is cooled to about 0° C. and an extract solvent composed of equal parts tetrahydrofuran and ethyl ether is added and residual hydride is quenched with water. 90 ml of 2N hydrochloric acid is added to complete hydrolysis. The solution is then extracted twice with ether, the aqueous phase is made alkaline (pH 9-10) with a saturated potassium carbonate solution and extracted with ether. The organic phases are combined, washed with saturated potassium carbonate solution, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to yield crude 2-phenyl-1,3-propanediol. Purified 2-phenyl-1,3-propanediol (mp 51°-53° C.) was obtained by recrystallization from a mixture of hexane/toluene/ether (10:5:1) in a yield of 72%.
Reaction SMILES: [OH:1][C:2]1[CH:15]=[CH:14][CH:13]=[CH:12][C:3]=1[C:4]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)=[O:5].C([O-])([O-])=O.[K+].[K+].[CH2:22](Cl)[O:23][CH3:24]>CC(C)=O.CCOC(C)=O>[CH3:22][O:23][CH2:24][O:1][C:2]1[CH:15]=[CH:14][CH:13]=[CH:12][C:3]=1[C:4]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)=[O:5]
Reactant: COCCl
Reactant: O=C(c1ccccc1)c1ccccc1O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Solvent: CCOC(C)=O
Product: COCOc1ccccc1C(=O)c1ccccc1
Temperature: 23 °C
Reaction time: 8 h
Yield: 16.5 %

Procedure:
To a stirring solution of 2-hydroxybenzophenone (3.0 g, 15.1 mmol) and K2CO3 (9.94 g, 71.9 mmol) in acetone (80 mL) under reflux was added MOMCl (2.9 mL, 37.8 mmol) and allowed to stir overnight. The reaction was then cooled to 23° C., diluted with EtOAc, washed with 2N NaOH (3×), the organic phase dried (Na2SO4), filtered and concentrated to provide the product (605 mg) as an oil: 1H NMR (400 MHz, DMSO-d6) δ ppm 7.67-7.72 (2H, m), 7.63 (1H, d, J=7.07 Hz), 7.48-7.54 (3H, m), 7.34 (1H, dd, J=7.33, 1.52 Hz), 7.24 (1H, d, J=8.34 Hz), 7.13 (1H, t, J=7.45 Hz), 5.08 (2H, s), 3.13 (3H, s).
Reaction SMILES: Cl.[NH:2]1[CH2:7][CH2:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([N:14]3[CH2:18][C@H:17]([CH2:19][N:20]4[CH:24]=[CH:23][N:22]=[N:21]4)[O:16][C:15]3=[O:25])=[CH:10][C:9]=2[F:26])=[CH:4][CH2:3]1.C(N(CC)CC)C.[CH:34](OCC)=[O:35]>C(OCC)(=O)C>[CH:34]([N:2]1[CH2:7][CH2:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([N:14]3[CH2:18][C@H:17]([CH2:19][N:20]4[CH:24]=[CH:23][N:22]=[N:21]4)[O:16][C:15]3=[O:25])=[CH:10][C:9]=2[F:26])=[CH:4][CH2:3]1)=[O:35]
Reactant: CCOC=O
Reactant: O=C1O[C@@H](Cn2ccnn2)CN1c1ccc(C2=CCNCC2)c(F)c1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: CCOC(C)=O
Product: O=CN1CC=C(c2ccc(N3C[C@H](Cn4ccnn4)OC3=O)cc2F)CC1

Procedure:
(5R)-3-(4-(1,2,5,6-Tetrahydropyridin-4-yl)-3-fluorophenyl)-5-(1,2,3-triazol-1-ylmethyl)-oxazolidin-2-one hydrochloride (450 mg, 1.19 mM) and triethylamine (156 mg, 1.56 mM) were heated under reflux for 48 hours in ethyl formate (20 ml). The reaction mixture was diluted with ethyl acetate (30 ml) and washed with water and brine. Drying (sodium sulfate) and evaporation gave a gum which crystallised on trituration with diethyl ether to give the desired product (358 mg).
Reaction SMILES: [C:1]([NH:4][C:5]1[CH:6]([CH2:13][CH2:14][CH2:15][CH2:16][C:17]([N:19]2[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]2)=[O:18])[S:7][CH2:8][C:9]=1[C:10]([OH:12])=O)(=[O:3])[CH3:2].C(N(CC)CC)C.Cl[C:33]([O:35][CH2:36][CH3:37])=[O:34]>CC(C)=O.O>[C:1]([NH:4][C:5]1[CH:6]([CH2:13][CH2:14][CH2:15][CH2:16][C:17]([N:19]2[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]2)=[O:18])[S:7][CH2:8][C:9]=1[C:10]([C:33]([O:35][CH2:36][CH3:37])=[O:34])=[O:12])(=[O:3])[CH3:2]
Reactant: CCOC(=O)Cl
Reactant: CC(=O)NC1=C(C(=O)O)CSC1CCCCC(=O)N1CCCCC1
Solvent: CC(C)=O
Solvent: O
Solvent: CCN(CC)CC
Product: CCOC(=O)C(=O)C1=C(NC(C)=O)C(CCCCC(=O)N2CCCCC2)SC1
Temperature: 0 °C
Reaction time: 1 h

Procedure:
2.12 g (0.0060 moles) of 3-acetamido-4-carboxy-2,5-dihydro-2-thiophenevaleric acid piperidide was dissolved in 25 ml acetone to which 1.3 ml water had been added, and the solution was cooled in an ice bath for 15 min. At this point 1.8 ml (.0063 mole) of triethylamine was added in 25 ml acetone, followed immediately by the dropwise addition of 1.23 ml. (0.0063 mole) of ethyl chloroformate in 2.7 ml of acetone over a 10 minute period. The reaction was stirred at 0°C. for one hour to form 3-acetamido-4-carbethoxycarbonyl-2,5-dihydro-2-thiophenevaleric acid piperidide, which was converted to 3-(N-carbethoxyacetamido)-4-carboxy-2,5-dihydro-2-thiophenevaleric acid piperidide, and which was converted to 3-(N-carbethoxyacetamido)-4-carbethoxycarbonyl-2,5-dihydro-2-thiophenevaleric acid piperidide. A solution of 0.8 g. (0.0063 mole) sodium azide in 5 ml. water was added dropwise over a period of 5 minutes. The reaction was further stirred at 0° C. for 2 hrs. The reaction mixture was then partitioned between 100 ml. of dichloromethane and 75 ml. of ice water. The aqueous phase was extracted three times with anhydrous sodium sulfate to yield 2.8 g. (0.0060 mole, 100%) of 4-azidocarbonyl-3-(N-carbethoxyacetamido)-2,5-dihydro-2-thiophenevaleric acid piperidide as a colorless oil.