Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH:1]1[CH2:4][CH:3]([N:5]2[CH2:10][CH2:9][N:8]([C:11]3[N:16]=[CH:15][CH:14]=[CH:13][N:12]=3)[CH2:7][CH2:6]2)[CH2:2]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[C:50]1([C:59]2[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=2)[CH:55]=[CH:54][C:53]([C:56](O)=[O:57])=[CH:52][CH:51]=1>CN(C=O)C.O>[C:50]1([C:59]2[CH:60]=[CH:61][CH:62]=[CH:63][CH:64]=2)[CH:51]=[CH:52][C:53]([C:56]([N:1]2[CH2:4][CH:3]([N:5]3[CH2:6][CH2:7][N:8]([C:11]4[N:12]=[CH:13][CH:14]=[CH:15][N:16]=4)[CH2:9][CH2:10]3)[CH2:2]2)=[O:57])=[CH:54][CH:55]=1
Reactant: c1cnc(N2CCN(C3CNC3)CC2)nc1
Reactant: O=C(O)c1ccc(-c2ccccc2)cc1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: O
Solvent: CN(C)C=O
Product: O=C(c1ccc(-c2ccccc2)cc1)N1CC(N2CCN(c3ncccn3)CC2)C1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To a solution of 2-(4-azetidin-3-yl-piperazin-1-yl)-pyrimidine (0.172 g, 0.87 mmol) and HATU (0.347 g, 0.913 mmol) in DMF (4 mL) was added DIPEA (0.607 mL, 3.48 mmol). The mixture was stirred at room temperature for 30 min and then biphenyl-4-carboxylic acid (0.87 mmol) was added. The resulting mixture was stirred at room temperature for 5 h. H2O (8 mL) was added and the resulting mixture extracted with EtOAc (3×). The organic layer was dried over MgSO4 and concentrated. The resulting residue was purified by HPLC to yield biphenyl-4-yl-[3-(4-pyrimidin-2-yl-piperazin-1-yl)-azetidin-1-yl]-methanone.
Reaction SMILES: COC1C=C(C=CC=1)C=O.[Cl:11][C:12]1[C:21]2[C:16](=[CH:17][C:18]([O:23][CH3:24])=[C:19](C)[CH:20]=2)[CH:15]=[CH:14][N:13]=1>>[Cl:11][C:12]1[C:21]2[C:16](=[CH:17][C:18]([O:23][CH3:24])=[CH:19][CH:20]=2)[CH:15]=[CH:14][N:13]=1.[Cl:11][C:12]1[C:21]2[C:16](=[CH:17][C:18]([OH:23])=[CH:19][CH:20]=2)[CH:15]=[CH:14][N:13]=1
Reactant: COc1cc2ccnc(Cl)c2cc1C
Agent: COc1cccc(C=O)c1
Product: COc1ccc2c(Cl)nccc2c1
Product: Oc1ccc2c(Cl)nccc2c1

Procedure:
The 1-chloro-6-methoxyisoquinoline was prepared according to Example 1A or from 3-methoxybenzaldehyde using the same procedure as in Example 5A. The 1-chloro-6-methoxy-7-methylisoquinoline was then demethylated according Example 1E to afford 1-chloro isoquinolin-6-ol.
Reaction SMILES: [C:1]1([S:7][C:8]2[CH:15]=[CH:14][C:11]([CH:12]=[O:13])=[CH:10][CH:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.S(=O)(=O)([OH:18])N.Cl([O-])=O.[Na+].[OH2:25]>CC(C)=O>[C:1]1([S:7]([C:8]2[CH:15]=[CH:14][C:11]([C:12]([OH:18])=[O:13])=[CH:10][CH:9]=2)=[O:25])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: NS(=O)(=O)O
Reactant: O=Cc1ccc(Sc2ccccc2)cc1
Reactant: O
Agent: [Na+]
Agent: [O-][Cl+][O-]
Solvent: CC(C)=O
Product: O=C(O)c1ccc(S(=O)c2ccccc2)cc1
Reaction time: 0.08 h

Procedure:
The solution of 4-phenylsulfanyl-benzaldehyde (0.2 g, 0.93 mmol) in acetone (10 mL) was cooled to 0° C. in an ice bath. A solution of sulfamic acid (0.272 g, 2.8 mmol) in water (1 mL) was added and allowed to stir for 5 minutes at same temperature. An aq. solution of sodium chlorite (0.338 g, 3.7 mmol in 1 mL) was added and thew reaction mixture was allowed to stir for 30 minutes. The progress of the reaction was monitored by TLC. The reaction mixture was diluted with water and the resulting precipitate was filtered, washed with water and dried to get the title compound.
Reaction SMILES: P(Cl)(Cl)(Cl)=O.[NH:6]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][C:13]=2[C:15]([O:17][CH3:18])=[O:16])[CH:8]=[CH:7]1.[Cl-].O[NH3+].O.[CH3:23][N:24](C)C=O>>[C:23]([C:8]1[C:9]2[C:14](=[C:13]([C:15]([O:17][CH3:18])=[O:16])[CH:12]=[CH:11][CH:10]=2)[NH:6][CH:7]=1)#[N:24]
Reactant: CN(C)C=O
Reactant: COC(=O)c1cccc2cc[nH]c12
Agent: [Cl-]
Agent: [NH3+]O
Solvent: O
Solvent: O=P(Cl)(Cl)Cl
Product: COC(=O)c1cccc2c(C#N)c[nH]c12
Temperature: 120 °C
Reaction time: 1 h

Procedure:
9.1 g of phosphoryl chloride are added to 30 ml of dimethylformamide with ice cooling at a reaction temperature of 20-30°. A solution of 8 g of methyl indole-7-carboxylate in dimethylformamide is added dropwise, during which the temperature rises to 40°. After one hour at 125°, the solution is added dropwise while still hot to a solution of 6.3 g of hydroxylammonium chloride in 40 ml of dimethylformamide, and the mixture is stirred at 120° C. for a further 15 minutes. The mixture is poured into water, extracted with ethyl acetate, filtered through neutral aluminium oxide and evaporated, giving 4.5 g of methyl 3-cyanoindole-7-carboxylate having a melting range of 212-213.5° (48.9% of theory).
Reaction SMILES: [NH2:1][C:2]1[CH:12]=[CH:11][C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])=[CH:4][CH:3]=1.[CH2:13](Br)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.CC1C(C)=C(C)C(C)=C(C)C(C)=[C-]PC=1>O>[CH2:13]([NH:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])=[CH:11][CH:12]=1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1
Reactant: CCOC(=O)c1ccc(N)cc1
Reactant: BrCc1ccccc1
Agent: Cc1[c-][pH]cc(C)c(C)c(C)c(C)c1C
Solvent: O
Product: CCOC(=O)c1ccc(NCc2ccccc2)cc1

Procedure:
A mixture of 16.5 g. of ethyl p-aminobenzoate, 8.55 g. of benzyl bromide and 45 ml. of hexamethylphosphorimide are heated in an oil bath at 110° C. for 20 hours. The mixture is diluted with water, chilled, filtered and the solid washed with water to give tan crystals, m.p. 90°-93° C. A sample is recrystallized from ethanol to give tan crystals, m.p. 96°-97° C.
Reaction SMILES: CON(C)[C:4](=[O:12])[C:5]1[C:6](=[CH:8][CH:9]=[CH:10][CH:11]=1)[NH2:7].[CH2:14]([O:21][C:22]1[CH:27]=[CH:26][C:25](Br)=[CH:24][CH:23]=1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.[Li]CCCC.Cl>O1CCCC1>[CH2:14]([O:21][C:22]1[CH:27]=[CH:26][C:25]([C:4](=[O:12])[C:5]2[CH:11]=[CH:10][CH:9]=[CH:8][C:6]=2[NH2:7])=[CH:24][CH:23]=1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1
Reactant: Brc1ccc(OCc2ccccc2)cc1
Reactant: CON(C)C(=O)c1ccccc1N
Agent: Cl
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: Nc1ccccc1C(=O)c1ccc(OCc2ccccc2)cc1
Reaction time: 0.33 h

Procedure:
To a mixture of N-methoxy-N-methyl anthranilic acid amide prepared as in Example 1(A)(2.00 g, 11.1 mmol) and 4-benzyloxy-bromobenzene (2.92 g, 11.1 mmol) in anhydrous tetrahydrofuran (65 ml) at -78° C. under nitrogen is added, with vigorous stirring, n-BuLi in hexanes (13.8 ml, 1.6M, 22.2 mmol) at 0.60 ml/min. After 20 min, aqueous hydrochloric acid is added (1N, 20 ml), the mixture extracted with ethyl acetate (150 ml), ethyl acetate washed with water, brine, dried over magnesium sulfate, and concentrated. Recrystallization from hexanes gave 4'-benzyloxy-2-aminobenzophenone as yellow crystals; yield: 2.35 g, (70%); m.p. 99°-101° C.
Reaction SMILES: FC(F)(F)S(OS(C(F)(F)F)(=O)=O)(=O)=O.[Si:16]([O:23][CH2:24][C:25]1([CH2:39][O:40][Si:41]([C:44]([CH3:47])([CH3:46])[CH3:45])([CH3:43])[CH3:42])[O:30][C:29]2[CH:31]=[CH:32][C:33]([N+:35]([O-:37])=[O:36])=[CH:34][C:28]=2[NH:27][C:26]1=O)([C:19]([CH3:22])([CH3:21])[CH3:20])([CH3:18])[CH3:17].[N-:48]=[N+:49]=[N-:50].[Na+]>CC#N>[Si:41]([O:40][CH2:39][C:25]1([CH2:24][O:23][Si:16]([C:19]([CH3:20])([CH3:21])[CH3:22])([CH3:17])[CH3:18])[O:30][C:29]2[CH:31]=[CH:32][C:33]([N+:35]([O-:37])=[O:36])=[CH:34][C:28]=2[N:27]2[N:48]=[N:49][N:50]=[C:26]12)([C:44]([CH3:45])([CH3:46])[CH3:47])([CH3:43])[CH3:42]
Reactant: CC(C)(C)[Si](C)(C)OCC1(CO[Si](C)(C)C(C)(C)C)Oc2ccc([N+](=O)[O-])cc2NC1=O
Reactant: [N-]=[N+]=[N-]
Agent: O=S(=O)(OS(=O)(=O)C(F)(F)F)C(F)(F)F
Agent: [Na+]
Solvent: CC#N
Product: CC(C)(C)[Si](C)(C)OCC1(CO[Si](C)(C)C(C)(C)C)Oc2ccc([N+](=O)[O-])cc2-n2nnnc21
Temperature: 25 °C
Reaction time: 8 h
Yield: 48.5 %

Procedure:
Trifluoromethanesulfonic anhydride (650 μL, 3.9 mmol) was added dropwise over 5 min to a stirred solution of 2,2-bis(((tert-butyldimethylsilyl)oxy)methyl)-6-nitro-2H-benzo[b][1,4]oxazin-3(4H)-one (0.62 g, 1.3 mmol) and NaN3 (0.50 g, 7.7 mmol) in MeCN (15 mL) at −10° C. (ice/MeOH bath) under nitrogen. The mixture was allowed to warm to room temperature slowly, then stirred at room temperature overnight. The mixture was then re-cooled to −10° C. and quenched by the addition of cold EtOAc (30 mL) followed by cold saturated NaHCO3 (30 mL) [note: saturated NaHCO3 solution was added over ca. 5 min]. Further EtOAc (50 mL) and H2O (30 mL) was added and the aqueous and organic layers were partitioned. The organic layer was dried (Na2SO4), filtered and the solvent removed under vacuum to leave a crude residue. The residue was dry-loaded on to silica gel and then purified by column chromatography on silica gel using hexane/DCM as eluent (1:0 to 0:1) to give the product (320 mg, 49% yield).
Reaction SMILES: [H-].[Na+].Cl[C:4]1[C:13]2[C:8](=[CH:9][C:10]([O:16][CH2:17][CH2:18]CN3CCOCC3)=C(OC)[CH:12]=2)N=CN=1>O1CCCC1.ClCCl.CO>[CH3:10][CH2:9][CH2:8][CH:13]([CH3:4])[CH3:12].[CH3:9][CH2:10][O:16][CH2:17][CH3:18]
Reactant: COc1cc2c(Cl)ncnc2cc1OCCCN1CCOCC1
Agent: [H-]
Agent: [Na+]
Solvent: CO
Solvent: C1CCOC1
Solvent: ClCCl
Product: CCCC(C)C
Product: CCOCC
Temperature: 70 °C
Yield: 353.5 %

Procedure:
Sodium hydride (500 mg of a 60% suspension in mineral oil, 10 mmol) was added to a solution of with 4-chloro-6-methoxy-7-(3-morpholinopropoxy)quinazoline (2.02 g, 6.0 mmol) 2-diethyoxymethyl-5-aminopyrimidine (1.0 g, 5.0 mmol) in tetrahydrofuran (25 ml) and the reaction was heated at 70° C. for 2 hours. The reaction was cooled and excess sodium hydride quenched by the addition of methanol (1 ml) followed by concentration to dryness. The residue was dissolved in dichloromethane/methanol 20:1 (30 ml) and poured quickly through silica gel (20 g in a sinter funnel). Elution with dichloromethane/methanol 20:1 yielded 4-(2-diethoxymethyl-5-aminopyrimidine)-6-methoxy-7-(3-morpholinopropoxy)quinazoline after trituration with isohexane/ether (1:1) as an off-white solid (1.7 g, 70% yield):
Reaction SMILES: [OH:1][CH:2]([CH:8]([N:15]([CH3:22])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[C:3](OCC)=[O:4].[CH3:23][NH2:24]>>[OH:1][CH:2]([CH:8]([N:15]([CH3:22])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[C:3]([NH:24][CH3:23])=[O:4]
Reactant: CCOC(=O)C(O)C(c1ccccc1)N(C)c1ccccc1
Reactant: CN
Product: CNC(=O)C(O)C(c1ccccc1)N(C)c1ccccc1
Temperature: 80 °C
Reaction time: 5 h
Yield: 99 %

Procedure:
A mixture of ethyl (2RS,3RS)-2-hydroxy-3-[methyl(phenyl)amino]-3-phenylpropanoate (Example 1, Step 1, 375 mg, 1.25 mmol) and ethanolic methylamine solution (33 weight % in absolute ethanol, 5 mL) was stirred at 80° C. in a sealed tube for 5 hours. After cooling, all volatiles were removed under reduced pressure. The resulting solid was recrystallized (warm chloroform/hexane/−25° C.) to yield 350 mg (99%) (2RS,3RS)-2-hydroxy-N-methyl-3-[methyl(phenyl)amino]-3-phenylpropanamide as white needles. MS (ESI) m/z 285 ([M+H]+); HRMS: calculated for C17H20N2O2+H, 285.1598; found (ESI, [M+H]+), 285.1592.
Reaction SMILES: [CH2:1]([C@@H:8]1[O:12][C:11]([CH3:14])([CH3:13])[O:10][C:9]1=[O:15])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Li+].CC([N-]C(C)C)C.[C:24]([O:28][CH3:29])(=[O:27])[CH:25]=[CH2:26]>C1COCC1>[CH3:29][O:28][C:24](=[O:27])[CH2:25][CH2:26][C:8]1([CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[C:9](=[O:15])[O:10][C:11]([CH3:13])([CH3:14])[O:12]1
Reactant: C=CC(=O)OC
Reactant: CC1(C)OC(=O)[C@H](Cc2ccccc2)O1
Agent: CC(C)[N-]C(C)C
Agent: [Li+]
Solvent: C1CCOC1
Product: COC(=O)CCC1(Cc2ccccc2)OC(C)(C)OC1=O
Yield: 53.6 %

Procedure:
To a solution of compound 56 (3.180 g, 15.42 mmol) in THF was added 9.42 mL LDA (1.8 M in THF, 16.96 mmol) at −78° C. Methyl acrylate (1.460 g, 16.96 mmol) was added to the solution at −78° C. after 15 min. After 1 h the reaction was quenched with saturated NH4Cl aqueous solution, extracted with EtOAc 3×30 mL, dried with MgSO4 and purified on silica gel with 8-17% EtOAc-PE which gave the title compound (2.418 g, 54%) as colorless oil.
Reaction SMILES: [C:1]1([N:7]2[C:19]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[C:13]3[C:8]2=[CH:9][CH:10]=[CH:11][CH:12]=3)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Br:20]N1C(=O)CCC1=O>C(O)(=O)C.CO>[Br:20][C:16]1[CH:17]=[CH:18][C:19]2[N:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)[C:8]3[C:13]([C:14]=2[CH:15]=1)=[CH:12][CH:11]=[CH:10][CH:9]=3
Reactant: O=C1CCC(=O)N1Br
Reactant: c1ccc(-n2c3ccccc3c3ccccc32)cc1
Solvent: CC(=O)O
Solvent: CO
Product: Brc1ccc2c(c1)c1ccccc1n2-c1ccccc1
Temperature: 25 °C
Reaction time: 12 h
Yield: 88.1 %

Procedure:
24.3 g (100 mmol) of 9-phenylcarbazole was put into a 2 L Meyer flask, and dissolved in 600 mL of glacial acetic acid. Then, 17.8 g (100 mmol) of N-bromosuccinimide was slowly added thereto, and the solution was stirred for about 12 hours at room temperature. This glacial acetic acid solution was dropped into 1 L of ice water while being stirred. A white solid precipitated was collected by suction filtration, and then washed with water three times. This solid was dissolved in 150 mL of diethyl ether, and the solution was washed with a saturated aqueous solution of sodium bicarbonate and then with water. The organic layer was dried with magnesium sulfate, the mixture was filtered, and the filtrate was concentrated. Thus, an oily substance was obtained. The oily substance was dissolved in about 50 mL of methanol. A precipitate of a white solid was produced by keeping this solution still. This solid was collected by suction filtration and dried. Then, 28.4 g (88% yield) of 3-bromo-9-phenylcarbazole was obtained as white powder.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[C:16](=[O:17])[C:15]2[C@@H:14]3[C:18]([CH3:20])([CH3:19])[C@@:11]([CH3:21])([CH2:12][CH2:13]3)[C:10]=2[NH:9]1.[CH3:22]I>CN(C)C=O.O.C(=O)(O)[O-].[Na+]>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[C:16](=[O:17])[C:15]2[C@@H:14]3[C:18]([CH3:20])([CH3:19])[C@@:11]([CH3:21])([CH2:12][CH2:13]3)[C:10]=2[N:9]1[CH3:22]
Reactant: CC1(C)[C@@H]2CC[C@@]1(C)c1[nH]n(-c3ccccc3Cl)c(=O)c12
Reactant: CI
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: Cn1c2c(c(=O)n1-c1ccccc1Cl)[C@H]1CC[C@]2(C)C1(C)C
Temperature: 80 °C
Yield: 4.4 %

Procedure:
A mixture of (4S,7R)-2-(2-chloro-phenyl)-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (Intermediate 10; 5.11 g, 16.9 mmol) and methyl iodide (1.05 mL, 16.9 mmol) in N,N-dimethylformamide (20 mL) was heated to 80° C. for 2 h. The reaction mixture was diluted with water (50 mL) and saturated sodium bicarbonate (150 mL) and extracted with ethyl acetate (2×200 mL). The organic extracts were combined, washed with brine, dried (sodium sulfate), filtered, evaporated, and purified using an ISCO CombiFlash® Sg100c chromatography system eluting with 10-100% ethyl acetate/hexanes to give (4S,7R)-2-(2-chloro-phenyl)-1,7,8,8-tetramethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (233 mg, 4%). ES(+)-MS (M+H) 317.
Reaction SMILES: [NH2:1][CH:2]([C:4]([OH:6])=[O:5])[CH3:3].C(N(CC)CC)C.C[Si](Cl)(C)C.[CH2:19]([CH:21]([CH2:25][CH3:26])[C:22](Cl)=[O:23])[CH3:20].[OH-].[Na+]>ClCCl.O>[CH3:20][CH2:19][CH:21]([CH2:25][CH3:26])[C:22]([NH:1][CH:2]([CH3:3])[C:4]([OH:6])=[O:5])=[O:23]
Reactant: CCC(CC)C(=O)Cl
Reactant: CC(N)C(=O)O
Agent: C[Si](C)(C)Cl
Agent: [Na+]
Agent: [OH-]
Solvent: ClCCl
Solvent: CCN(CC)CC
Solvent: O
Product: CCC(CC)C(=O)NC(C)C(=O)O
Temperature: 0 °C
Reaction time: 1 h

Procedure:
24.5 g (0.275 mol) of D,L-alanine are initially charged in 250 ml of dichloromethane, and 61.2 g (0.605 mol) of triethylamine are added. The mixture is cooled to 0° C., and 65.7 g (0.605 mol) of trimethylsilyl chloride are added. The mixture is stirred at room temperature for one hour and at 40° C. for one hour. The mixture is cooled to −10° C., and 37 g (0.275 mol) of 2-ethylbutyryl chloride are slowly added dropwise. The mixture is stirred at −10° C. for two hours and at room temperature overnight. The mixture is cooled in an ice bath, and 150 ml of water are added. 50 g (1.25 mol) of NaOH, dissolved in 100 ml of water, are added and the aqueous phase is separated off and concentrated. The residue is again taken up in water and acidified with concentrated hydrochloric acid, the aqueous solution is extracted repeatedly with dichloromethane and the organic phase is dried over Na2SO4 and concentrated.
Reaction SMILES: CS(O[C@H:6]([C@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14]1[CH:19]=[CH:18][N:17]=[C:16]([NH:20][C@H:21]([C:23]2[S:27][C:26]([C:28]3[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][CH:29]=3)=[N:25][CH:24]=2)[CH3:22])[N:15]=1)[CH3:7])(=O)=O.[N-:35]=[N+:36]=[N-:37].[Na+]>CN(C=O)C.O>[N:35]([C@@H:6]([C@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14]1[CH:19]=[CH:18][N:17]=[C:16]([NH:20][C@H:21]([C:23]2[S:27][C:26]([C:28]3[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][CH:29]=3)=[N:25][CH:24]=2)[CH3:22])[N:15]=1)[CH3:7])=[N+:36]=[N-:37]
Reactant: [N-]=[N+]=[N-]
Reactant: C[C@H](Nc1nccc(N2C(=O)OC[C@@H]2[C@H](C)OS(C)(=O)=O)n1)c1cnc(-c2ccc(Cl)cc2)s1
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: C[C@H](Nc1nccc(N2C(=O)OC[C@@H]2[C@@H](C)N=[N+]=[N-])n1)c1cnc(-c2ccc(Cl)cc2)s1
Temperature: 50 °C
Reaction time: 42 h
Yield: 75 %

Procedure:
To a microwave vial containing (S)-1-((R)-3-(2-(((S)-1-(2-(4-chlorophenyl)thiazol-5-yl)ethyl)amino)pyrimidin-4-yl)-2-oxooxazolidin-4-yl)ethyl methanesulfonate (21 mg, 0.04 mmol) in DMF (1 mL) was added sodium azide (13 mg, 0.20 mmol). Resulting reaction mixture heated to 50° C. for 1 hr in a sand bath then to 80° C. for 42 hr. Reaction mixture was diluted with water and extracted with EtOAc. Organic phases combined, washed with brine, dried (Na2SO4), filtered and concentrated to a yellow residue of (S)-4-((R)-1-azidoethyl)-3-(2-(((S)-1-(2-(4-chlorophenyl)thiazol-5-yl)ethyl)amino)pyrimidin-4-yl)oxazolidin-2-one (14 mg, 0.030 mmol, 74.2% yield). LCMS m/z 471.2 (M+H)+, Rt 0.92 min.
Reaction SMILES: [C:1]([C:9]1[CH:10]=[N:11][C:12]2[C:17]([C:18]=1[C:19]1[CH:20]=[C:21]([CH:24]=[CH:25][CH:26]=1)[CH:22]=O)=[CH:16][CH:15]=[CH:14][C:13]=2[C:27]([F:30])([F:29])[F:28])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([O:33][C:34](=[O:43])[CH2:35][C:36]1[CH:41]=[CH:40][C:39]([NH2:42])=[CH:38][CH:37]=1)C>>[C:1]([C:9]1[CH:10]=[N:11][C:12]2[C:17]([C:18]=1[C:19]1[CH:20]=[C:21]([CH:24]=[CH:25][CH:26]=1)[CH2:22][NH:42][C:39]1[CH:38]=[CH:37][C:36]([CH2:35][C:34]([OH:33])=[O:43])=[CH:41][CH:40]=1)=[CH:16][CH:15]=[CH:14][C:13]=2[C:27]([F:30])([F:29])[F:28])(=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=Cc1cccc(-c2c(C(=O)c3ccccc3)cnc3c(C(F)(F)F)cccc23)c1
Reactant: CCOC(=O)Cc1ccc(N)cc1
Product: O=C(O)Cc1ccc(NCc2cccc(-c3c(C(=O)c4ccccc4)cnc4c(C(F)(F)F)cccc34)c2)cc1

Procedure:
The title compound was prepared from 3-[3-benzoyl-8-(trifluoromethyl)quinolin-4-yl]benzaldehyde and (4-amino-phenyl)-acetic acid ethyl ester according to the procedure of Example 66. MS m/z 541.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([OH:14])=[CH:10][CH:9]=2)=[CH:4][CH:3]=1.C1(NC2CCCCC2)CCCCC1.[P:28]([O-:33])([O:31]C)[O:29][CH3:30]>CC(C)=O>[CH3:30][O:29][P:28]([OH:33])([O:14][CH3:11])=[O:31].[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=2)=[CH:4][CH:3]=1
Reactant: Cc1ccc(-c2ccc(O)cc2)cc1
Reactant: COP([O-])OC
Agent: C1CCC(NC2CCCCC2)CC1
Solvent: CC(C)=O
Product: COP(=O)(O)OC
Product: Cc1ccc(-c2ccccc2)cc1
Temperature: 25 °C
Yield: 188.8 %

Procedure:
A mixture of 4′-methyl-4-hydroxybiphenyl (4.3 g, 23.4 mmol) and dicyclohexylamine (5.2 mL, 26.1 mmol) in acetone (30 mL) was refluxed for 1 h. Solvent was then evaporated in vacuo. The residue was dissolved in CCl4 (120 mL) and mixed with dimethyl phosphite (2.4 mL, 26.2 mmol). The mixture was refluxed for 4 h., cooled to r.t. and filtered. The filtrate was concentrated and chromatographed over silica gel eluting with hexanes:EtOAc (2:3) to give 6.5 g (95%) of the title compound as a white solid.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[CH:17]=[CH:16][CH:15]=[C:14]3[C:10]=2[CH2:11][C:12](=[O:18])[NH:13]3)[CH:5]=[CH:6][C:7]=1[F:8].[N:19]1([CH2:24][CH2:25][NH:26][C:27]([C:29]2[CH:33]=[C:32]([CH3:34])[NH:31][C:30]=2[CH:35]=O)=[O:28])[CH:23]=[CH:22][N:21]=[N:20]1>C(O)C.N1CCCCC1>[N:19]1([CH2:24][CH2:25][NH:26][C:27]([C:29]2[CH:33]=[C:32]([CH3:34])[NH:31][C:30]=2[CH:35]=[C:11]2[C:10]3[C:14](=[CH:15][CH:16]=[CH:17][C:9]=3[C:4]3[CH:5]=[CH:6][C:7]([F:8])=[C:2]([Cl:1])[CH:3]=3)[NH:13][C:12]2=[O:18])=[O:28])[CH:23]=[CH:22][N:21]=[N:20]1
Reactant: Cc1cc(C(=O)NCCn2ccnn2)c(C=O)[nH]1
Reactant: O=C1Cc2c(cccc2-c2ccc(F)c(Cl)c2)N1
Solvent: CCO
Solvent: C1CCNCC1
Product: Cc1cc(C(=O)NCCn2ccnn2)c(C=C2C(=O)Nc3cccc(-c4ccc(F)c(Cl)c4)c32)[nH]1
Temperature: 25 °C
Reaction time: 72 h
Yield: 69.3 %

Procedure:
To a solution of 4-(3-chloro-4-fluoro-phenyl)-1,3-dihydro-indol-2-one (65.4 mg, 0.25 mmol) and 2-formyl-5-methyl-1H-pyrrole-3-carboxylic acid (2-[1,2,3]triazol-1-yl-ethyl)-amide (61.8 mg, 0.26 mmol) in ethanol (2 mL) was added piperidine (3 drops). The reaction mixture was stirred at room temperature for three days. A yellow solid product was precipitated out, filtered, washed by ethanol for three times, and dried under high vacuum to provide pure product 2-[4-(3-chloro-4-fluoro-phenyl)-2-oxo-1,2-dihydro-indol-3-ylidenemethyl]-5-methyl-1H-pyrrole-3-carboxylic acid (2-[1,2,3]triazol-1-yl-ethyl)-amide as a yellow solid (85 mg, 69%).
Reaction SMILES: [F:1][C:2]([F:9])([F:8])[CH:3]([F:7])[CH:4](F)[F:5].[OH-].[K+:11]>O>[F:5][CH:4]=[C:3]([F:7])[C:2]([F:9])([F:8])[F:1].[F-:1].[K+:11]
Reactant: FC(F)C(F)C(F)(F)F
Agent: [K+]
Agent: [OH-]
Solvent: O
Product: FC=C(F)C(F)(F)F
Product: [F-]

Procedure:
According to a particularly preferred embodiment (FIG. 1) of the invention, (i) hexafluoropropylene (1) is reacted continuously with hydrogen (2) in the gas phase in a superstoichiometric amount, in an adiabatic reactor (100), in the presence of a catalyst, to give 1,1,1,2,3,3-hexafluoropropane, and a portion (13) of the gaseous output stream resulting from this reaction is recycled; (ii) the nonrecycled part (3) of the output stream resulting from stage (i), comprising 1,1,1,2,3,3-hexafluoropropane, is reacted with potassium hydroxide (4) present in an aqueous reaction medium (200), in an amount of between 20 and 75% by weight and preferably of between 55 and 70% by weight, with respect to the weight of the water and KOH mixture of the reaction medium, maintained at a temperature of between 80 and 180° C., preferably of between 145 and 165° C., to give 1,2,3,3,3-pentafluoro-1-propene and potassium fluoride; (iii) the 1,2,3,3,3-pentafluoro-1-propene (6) obtained in stage (ii) is reacted with hydrogen (2) in the gas phase in a superstoichiometric amount, in an adiabatic reactor (300), in the presence of a catalyst, to give 1,1,1,2,3-penta-fluoropropane and a portion (14) of the gaseous output stream resulting from this reaction is recycled; (iv) the nonrecycled portion (7) of the output stream resulting from stage (iii), comprising 1,1,1,2,3-pentafluoropropane, is subjected to a purification stage (400) in order to remove impurities (8) and thus to obtain 1,1,1,2,3-pentafluoropropane, with a purity preferably of greater than 98% by weight; (v) the 1,1,1,2,3-pentafluoropropane obtained after the purification of stage (iv) is reacted with potassium hydroxide (4) present in an aqueous reaction medium (500), in an amount of between 20 and 75% by weight and preferably of between 55 and 70% by weight, with respect to the weight of the water and KOH mixture of the reaction medium, maintained at a temperature of between 80 and 180° C., preferably of between 145 and 165° C., to give 2,3,3,3-tetrafluoro-1-propene and potassium fluoride; and (vi) the gas stream (9) resulting from the dehydrofluorination stage (v), comprising HFO-1234yf, the unreacted HFC-245eb and the by products, is subjected to a purification stage (600) in order to obtain HFO-1234yf (12) having a purity of greater than 99.5% by weight, preferably of greater than 99.8% by weight. The light by products (10) separated from HFO-1234yf can be subjected to a treatment and the unreacted HFC-245eb (11) can be recycled in (500).