Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([NH2:13])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12].[O:14]1[CH:18]([CH2:19][OH:20])[CH:15]1[CH2:16][OH:17]>>[CH2:1]([NH:13][CH:18]([CH:15]([OH:14])[CH2:16][OH:17])[CH2:19][OH:20])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12]
Reactant: CCCCCCCCCCCCN
Reactant: OCC1OC1CO
Product: CCCCCCCCCCCCNC(CO)C(O)CO

Procedure:
Dodecylamine (185 g, 1.0 mole) was charged into a 500 ml round bottom flask equipped with a stirrer, thermometer (with temperature controller) and powder dropping funnel. Then 2,3-epoxy-1,4 butandiol (26 g, 0.4 moles) was placed in the dropping funnel. The mixture was stirred and heated while epoxide was being added so that suitable dissolution and reaction could occur. Upon completion of such addition the temperature of the reaction mixture was 100° C. The resulting mixture was stirred for 3 hours at 100° C. and distilled with a molecular still at 125° C. and <1 mm to remove excess dodecylamine. The resultant non-volatile product was cooled to give a light tan solid whose IR and NMR spectra were consistent with the formula ##STR8## where n=1.
Reaction SMILES: [Cl:1][CH2:2][CH2:3][O:4][C:5]1[C:21]([O:22][CH3:23])=[CH:20][C:8]2[CH:9]=[C:10]3[C:15](=[CH:16][C:7]=2[CH:6]=1)[NH:14][CH:13]=[C:12]([C:17]#[N:18])[C:11]3=O.N1C2C(=CC=CC=2)C=C(C#N)C=1.P(Cl)(Cl)([Cl:38])=O>CN(C)C=O>[Cl:38][C:11]1[C:10]2[C:15](=[CH:16][C:7]3[CH:6]=[C:5]([O:4][CH2:3][CH2:2][Cl:1])[C:21]([O:22][CH3:23])=[CH:20][C:8]=3[CH:9]=2)[N:14]=[CH:13][C:12]=1[C:17]#[N:18]
Reactant: COc1cc2cc3c(=O)c(C#N)c[nH]c3cc2cc1OCCCl
Reactant: O=P(Cl)(Cl)Cl
Agent: N#Cc1cnc2ccccc2c1
Solvent: CN(C)C=O
Product: COc1cc2cc3c(Cl)c(C#N)cnc3cc2cc1OCCCl
Yield: 87 %

Procedure:
To a slurry of 1.11 g of 8-(2-chloroethoxy)-7-methoxy-4-oxo-1,4-dihydrobenzo[g]quinoline-3-carbonitrile and 7-(2-chloroethoxy)-8-methoxy-4-oxo-1,4-dihydrobenzo]quinoline-3-carbonitrile (1:1 mixture) and 5 mL of phosphorus oxychloride is added 0.15 mL of anhydrous dimethylformamide. This is stirred and heated to reflux for 20 minutes using an oil bath, followed concentration in vacuo. The dark residue is quenched with 30 mL of cold water. The solid formed is collected, washed with water and dried to give 1.02 g (87%) of 4-chloro-7-methoxy-8(2-chloroethoxy)benzo[g]quinoline-3-carbonitrile and 4-chloro-8-methoxy-7(2-chloroethoxy)benzo[g]quinoline-3-carbonitrile (1:1 mixture) as a greenish yellow solid, m.p. 195–209° C. dec.
Reaction SMILES: [CH:1]1([CH2:4][N:5]2[C:10](=[O:11])[C:9]([CH2:12][NH:13][CH3:14])=[CH:8][C:7]([C:15]3[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[C:17]([F:23])[CH:16]=3)=[N:6]2)[CH2:3][CH2:2]1.C1(CN2[C:33](=[O:34])C(COS(C)(=O)=O)=CC(C3C=CC(OC)=C(F)C=3)=N2)CC1.NCCO>>[CH:1]1([CH2:4][N:5]2[C:10](=[O:11])[C:9]([CH2:12][NH:13][CH2:14][CH2:33][OH:34])=[CH:8][C:7]([C:15]3[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[C:17]([F:23])[CH:16]=3)=[N:6]2)[CH2:3][CH2:2]1
Reactant: COc1ccc(-c2cc(COS(C)(=O)=O)c(=O)n(CC3CC3)n2)cc1F
Reactant: CNCc1cc(-c2ccc(OC)c(F)c2)nn(CC2CC2)c1=O
Solvent: NCCO
Product: COc1ccc(-c2cc(CNCCO)c(=O)n(CC3CC3)n2)cc1F
Yield: 72.1 %

Procedure:
Following the procedure of Example 9 (4), 2-cyclopropylmethyl-6-(3-fluoro-4-methoxyphenyl)-4-methane-sulfonyloxymethyl-2H-pyridazin-3-one and 2-aminoethanol were reacted to yield the title compound as a yellow oil (yield: 72.1%).
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[O:10][CH:11]([F:13])[F:12])[CH:5]=[O:6].C(=O)([O-])[O-].[K+].[K+].Br[CH2:21][CH:22]1[CH2:24][CH2:23]1>CN(C)C=O>[CH:22]1([CH2:21][O:1][C:2]2[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=2[O:10][CH:11]([F:12])[F:13])[CH:5]=[O:6])[CH2:24][CH2:23]1
Reactant: O=Cc1ccc(OC(F)F)c(O)c1
Reactant: BrCC1CC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: O=Cc1ccc(OC(F)F)c(OCC2CC2)c1
Temperature: 65 °C
Reaction time: 1.5 h
Yield: 104.8 %

Procedure:
To a mixture of 3-hydroxy-4-difluoromethoxybenzaldehyde (19.55 g, 104 mmol) and potassium carbonate (21.56 g, 156 mmol) in dimethylformamide (150 mL) under an argon atmosphere at 60° C. was added bromomethylcyclopropane (15.13 mL, 156 mmol) and the mixture was stirred and heated at 65° C. After 1.5 h, the mixture was allowed to cool and was filtered. The filtrate was concentrated under reduced pressure and the residue was partitioned between ethyl acetate and water and was extracted four times with ethyl acetate. The organic extract was washed twice with water and was dried (sodium sulfate). The solvent was removed in vacuo to provide an oil (26.4 g).
Reaction SMILES: Br[CH2:2][CH2:3][C:4]1[CH:16]=[CH:15][C:7]([C:8]([NH:10][S:11]([CH3:14])(=[O:13])=[O:12])=[O:9])=[CH:6][CH:5]=1.N12CCCN=C1CCCCC2>C1COCC1>[CH:3]([C:4]1[CH:16]=[CH:15][C:7]([C:8]([NH:10][S:11]([CH3:14])(=[O:12])=[O:13])=[O:9])=[CH:6][CH:5]=1)=[CH2:2]
Reactant: CS(=O)(=O)NC(=O)c1ccc(CCBr)cc1
Solvent: C1CCC2=NCCCN2CC1
Solvent: C1CCOC1
Product: C=Cc1ccc(C(=O)NS(C)(=O)=O)cc1

Procedure:
N-(4-vinylbenzoyl)methanesulfonarnide was prepared according to step 2 of Example 1 from N-[4-(2-bromoethyl)benzoyl]methanesulfonamide and 1,8-diazabicyclo-[5.4.0]undec-7-ene (DBU) in THF.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:17]=[CH:16][C:6]([C:7]([NH:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[O:8])=[CH:5][C:4]=1[CH2:18][NH2:19].[Cl:20][C:21]1[CH:22]=[C:23]([N:28]=[C:29]=[S:30])[CH:24]=[C:25]([Cl:27])[CH:26]=1>C(N(CC)CC)C>[Cl:20][C:21]1[CH:22]=[C:23]([NH:28][C:29](=[S:30])[NH:19][CH2:18][C:4]2[CH:5]=[C:6]([CH:16]=[CH:17][C:3]=2[O:2][CH3:1])[C:7]([NH:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[O:8])[CH:24]=[C:25]([Cl:27])[CH:26]=1
Reactant: COc1ccc(C(=O)Nc2ccccc2)cc1CN
Reactant: S=C=Nc1cc(Cl)cc(Cl)c1
Solvent: CCN(CC)CC
Product: COc1ccc(C(=O)Nc2ccccc2)cc1CNC(=S)Nc1cc(Cl)cc(Cl)c1
Temperature: 50 °C
Yield: 27 %

Procedure:
A mixture of the product from Step C (0.1585 g, 0.54 mmol), triethylamine (0.5 mL) and 3,5-dichlorophenyl isothiocyanate (Lancaster) (0.138 g, 0.68 mmol) was heated briefly to 50° C. and then allowed to stand at room temperature over-night. The reaction mixture was then re-warmed to 50° C., filtered, and concentrated to an oil which was triturated in hexanes/ethyl acetate (2:1) and filtered through silica gel in ethyl acetate to afford the product (0.067 g); m.p. 208-210° C.
Reaction SMILES: [CH:1]1([CH:4]2[C:13]3[C:8](=[CH:9][C:10]([O:16][CH3:17])=[C:11]([O:14][CH3:15])[CH:12]=3)[CH2:7][CH2:6][NH:5]2)[CH2:3][CH2:2]1.COCC(Cl)=O.[CH:24]1(C(Cl)=O)[CH2:26][CH2:25]1>>[CH2:1]([CH:4]1[C:13]2[C:8](=[CH:9][C:10]([O:16][CH3:17])=[C:11]([O:14][CH3:15])[CH:12]=2)[CH2:7][CH2:6][NH:5]1)[CH2:3][CH2:2][CH2:25][CH2:24][CH3:26]
Reactant: COc1cc2c(cc1OC)C(C1CC1)NCC2
Reactant: O=C(Cl)C1CC1
Agent: COCC(=O)Cl
Product: CCCCCCC1NCCc2cc(OC)c(OC)cc21

Procedure:
1,2,3,4-Tetrahydro-1-hexyl-6,7-dimethoxyisoquinoline was prepared by a procedure analogous to that described in example 4 for 1,2,3,4-tetrahydro-1-cyclopropyl-6,7- dimethoxyisoquinoline but substituting in the first step 2-methoxyacetyl chloride for cyclopropylcarbonyl chloride.
Reaction SMILES: [Li]N1C(C)(C)CCC[C:3]1(C)C.[CH3:12][O:13][C:14]1[C:23]2[C:18](=[C:19]([CH3:28])[C:20]([O:26][CH3:27])=[C:21]([O:24][CH3:25])[CH:22]=2)[CH:17]=[C:16]([C:29]([OH:31])=[O:30])[CH:15]=1.CI.O>C1COCC1>[CH2:28]([C:19]1[C:20]([O:26][CH3:27])=[C:21]([O:24][CH3:25])[CH:22]=[C:23]2[C:18]=1[CH:17]=[C:16]([C:29]([OH:31])=[O:30])[CH:15]=[C:14]2[O:13][CH3:12])[CH3:3]
Reactant: [Li]N1C(C)(C)CCCC1(C)C
Reactant: COc1cc2c(OC)cc(C(=O)O)cc2c(C)c1OC
Solvent: CI
Solvent: O
Solvent: C1CCOC1
Product: CCc1c(OC)c(OC)cc2c(OC)cc(C(=O)O)cc12
Temperature: 0 °C
Reaction time: 2 h
Yield: 90 %

Procedure:
LTMP (7.5 mmol) is added at 0° C. to a solution of 4,6,7-trimethoxy-8-methyl-2-naphthoic acid (0.414 g, 1.5 mmol) in anhydrous THF (30 mL). The mixture is stirred for 2 h at 0° C. then trapped with MeI (0.943 mL, 15 mmol). After 2 h at 0° C., the reaction mixture is heated to ambient temperature and then hydrolysed with 30 mL of water. The aqueous phase is washed with ethyl ether (2×20 mL), acidified with 2M HCl (pH 1-2), then extracted with ethyl ether (3×30 mL). The combined organic phases are dried over MgSO4, filtered, then concentrated under reduced pressure. The residue is recrystallized (cyclohexane/ethyl acetate) to give 8-ethyl-4,6,7-trimethoxy-2-naphthoic acid (3) (0.392 g, 90%). 1H NMR (200 MHz, acetone-d6): 8.22 (s, 1H), 7.44 (s, 1H), 7.29 (s, 1H), 3.96 (s, 3H, OCH3), 3.89 (s, 3H, OCH3), 3.78 (s, 3H, OCH3), 3.02 (q, 2H, CH2), 1.16 (t, 3H, CH3). 13C NMR (100 MHz, DMSO-d6): 167.8, 154.2, 153.2, 146.9, 132.9, 127.0, 126.5, 125.0, 118.5, 102.6, 99.6, 60.6, 55.6, 55.4, 18.6, 15.4. IR (cm−1): 2940, 2826, 2637, 1682, 1464. SMHR, [M+H]+ calculated for C16H19O5: 291.1232. Found: 291.1230.
Reaction SMILES: [C:1]([O:4][CH2:5][C@H:6]1[C@@H:11]([N:12]2[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[CH2:14][CH2:13]2)[CH2:10][CH2:9][NH:8][CH2:7]1)(=[O:3])[CH3:2].C(N(CC)CC)C.[F:28][C:29]1[CH:37]=[CH:36][C:32]([CH2:33][CH2:34]Br)=[CH:31][CH:30]=1.O>CN(C)C=O.CO>[F:28][C:29]1[CH:37]=[CH:36][C:32]([CH2:33][CH2:34][N:8]2[CH2:9][CH2:10][C@H:11]([N:12]3[C:20]4[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=4)[CH2:14][CH2:13]3)[C@H:6]([CH2:5][O:4][C:1](=[O:3])[CH3:2])[CH2:7]2)=[CH:31][CH:30]=1
Reactant: CC(=O)OC[C@@H]1CNCC[C@@H]1N1CCc2ccccc21
Reactant: Fc1ccc(CCBr)cc1
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Solvent: O
Product: CC(=O)OC[C@@H]1CN(CCc2ccc(F)cc2)CC[C@@H]1N1CCc2ccccc21
Temperature: 50 °C
Reaction time: 2 h
Yield: 24.7 %

Procedure:
cis-1-(3-Acetoxymethylpiperidin-4-yl)indoline (280 mg) was dissolved in dimethylformamide (4 ml) and methanol (1 ml). To the resultant solution were added triethylamine (222 mg) and 4-fluorophenethyl bromide (285 mg) followed by stirring at 50° C. for 2 hr. Then the reaction mixture was cooled and water (50 ml) was added thereto. After extracting with ether (50 ml) twice, the organic phase was washed with water (20 ml) twice and a 2 N aqueous solution (50 ml) of sodium hydroxide once and dried over anhydrous magnesium sulfate. Then the solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography (hexane/ethyl acetate system) to give the title compound (100 mg) as a colorless oil (yield: 28%).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:17])[C:4]1[CH:9]=[C:8]([C:10]#[C:11][Si:12]([CH3:15])([CH3:14])[CH3:13])[C:7]([NH2:16])=[N:6][CH:5]=1.N1C=CC=CC=1.[C:24](Cl)(=[O:26])[CH3:25]>ClCCl>[CH3:1][O:2][C:3](=[O:17])[C:4]1[CH:9]=[C:8]([C:10]#[C:11][Si:12]([CH3:15])([CH3:14])[CH3:13])[C:7]([NH:16][C:24](=[O:26])[CH3:25])=[N:6][CH:5]=1
Reactant: CC(=O)Cl
Reactant: COC(=O)c1cnc(N)c(C#C[Si](C)(C)C)c1
Solvent: ClCCl
Solvent: c1ccncc1
Product: COC(=O)c1cnc(NC(C)=O)c(C#C[Si](C)(C)C)c1
Temperature: 25 °C
Reaction time: 12 h

Procedure:
To a solution of 6-amino-5-trimethylsilanylethynyl-nicotinic acid methyl ester (6.05 g, 24.4 mmol) and pyridine (4 mL, 49.4 mmol) in dichloromethane (80 mL) was added acetyl chloride (2.6 mL, 35.6 mmol) at 0° C. The mixture was allowed to warm up to 25° C. and stirred for 12 h. The reaction mixture was extracted with ethyl acetate, washed with brine and dried over sodium sulfate. The solvent was evaporated in vacuo to afford 6-acetylamino-5-trimethylsilanylethynyl nicotinic acid methyl ester which was used without further purification.
Reaction SMILES: [OH:1][C:2]1[C:7]2[O:8][C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=3[C:6]=2[C:5]([CH:15]=[O:16])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[CH:23](Br)([CH3:25])[CH3:24]>CN(C=O)C.O>[CH:23]([O:1][C:2]1[C:7]2[O:8][C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=3[C:6]=2[C:5]([CH:15]=[O:16])=[CH:4][CH:3]=1)([CH3:25])[CH3:24]
Reactant: CC(C)Br
Reactant: O=Cc1ccc(O)c2oc3ccccc3c12
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: CC(C)Oc1ccc(C=O)c2c1oc1ccccc12
Temperature: 80 °C
Reaction time: 0.17 h
Yield: 100.1 %

Procedure:
Intermediate 19 (500 mg, 2.358 mmol) was dissolved in dry DMF (5 ml). Anhydrous potassium carbonate (650 mg, 4.716 mmol) was added to the above solution and was stirred for 10 min. at 80° C. To this was added isopropyl bromide (431 mg, 3.537mmol) and the reaction mixture was stirred for 4 hrs. The reaction mixture was cooled to room temperature and diluted with water (100 ml) and extracted with ethyl acetate (3×50 ml). The organic extract was washed with water (50 ml) and brine solution (25 ml) and dried over anhydrous sodium sulfate. Removal of solvent gave the product as a white solid (600 mg).
Reaction SMILES: [Sb:1]=[O:2].O=[Si]=O.[O-2].[O-2].[O-2].[Sb+3].[Sb+3].[CH2:11]=[CH:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[C:19](#[N:22])[CH:20]=[CH2:21]>>[Sb:1]=[O:2].[CH3:11][C:12]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[CH2:19].[C:19](#[N:22])[CH:20]=[CH2:21]
Reactant: C=Cc1ccccc1
Agent: O=[Sb]
Agent: O=[Si]=O
Agent: [O-2]
Solvent: C=CC#N
Product: C=C(C)c1ccccc1

Procedure:
An aqueous colloidal dispersion of antimony oxide sold by Nyacol, Inc., Ashland, Mass. under the trade name Nyacol A-1530, containing 30 weight percent antimony oxide was added to an aqueous anionic latex containing 40 weight percent of polybutadiene grafted with 20 parts of an interpolymer containing 70 percent styrene and 30 percent acrylonitrile per 100 parts of polybutadiene and was stirred to provide a uniform blend. The procedure of Example 1 was then carried out to obtain a blend of rubber-occluded antimony oxide in an interpolymer of α-methylstyrene and acrylonitrile. The ratio of styrenic interpolymer to "ungrafted" polybutadiene to colloidal antimony was 22:8:1.
Reaction SMILES: C(N(CC)CC)C.[OH:8][CH2:9][CH2:10][C:11]1([C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[C:19]([Cl:24])[CH:18]=2)[CH2:16][CH2:15][CH2:14][NH:13][CH2:12]1.[CH:25]([O:28][C:29]1[CH:30]=[C:31]([CH2:35][C:36](O)=[O:37])[CH:32]=[CH:33][CH:34]=1)([CH3:27])[CH3:26].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>C(Cl)Cl>[OH:8][CH2:9][CH2:10][C:11]1([C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[C:19]([Cl:24])[CH:18]=2)[CH2:16][CH2:15][CH2:14][N:13]([C:36](=[O:37])[CH2:35][C:31]2[CH:32]=[CH:33][CH:34]=[C:29]([O:28][CH:25]([CH3:26])[CH3:27])[CH:30]=2)[CH2:12]1
Reactant: CC(C)Oc1cccc(CC(=O)O)c1
Reactant: OCCC1(c2ccc(Cl)c(Cl)c2)CCCNC1
Agent: CN(C)[P+](On1nnc2ccccc21)(N(C)C)N(C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(C)Oc1cccc(CC(=O)N2CCCC(CCO)(c3ccc(Cl)c(Cl)c3)C2)c1
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
22.5 ml of triethylamine and then 22 g of the 3-(2-hydroxyethyl)-3-(3,4-dichlorophenyl)piperidine (-) prepared above according to PREPARATION III (f) are added to a solution of 16 g of 3-isopropoxyphenylacetic acid in 500 ml of CH2Cl2. The mixture is cooled to 0° C., 42.6 g of BOP are then added and the reaction mixture is allowed to warm up to room temperature. After 30 minutes, the mixture is concentrated under vacuum and the residue is taken up in ether and washed successively with water, a dilute solution of NaOH, a saturated solution of NaCl, a dilute solution of HCl, a saturated solution of NaCl and a solution of NaHCO3. The ether phase is dried over MgSO4, filtered and concentrated under vacuum to give 36 g of optically pure product.
Reaction SMILES: [CH:1](Cl)([F:3])[F:2].[OH:5][C:6]1[CH:7]=[C:8]2[C:12](=[CH:13][CH:14]=1)[N:11]([C:15]1[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=1)[C:10]([CH3:23])=[C:9]2[C:24]([O:26][CH2:27][CH3:28])=[O:25].[OH-].[Na+].O>C(Cl)Cl.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC>[F:2][CH:1]([F:3])[O:5][C:6]1[CH:7]=[C:8]2[C:12](=[CH:13][CH:14]=1)[N:11]([C:15]1[CH:16]=[CH:17][C:18]([O:21][CH3:22])=[CH:19][CH:20]=1)[C:10]([CH3:23])=[C:9]2[C:24]([O:26][CH2:27][CH3:28])=[O:25]
Reactant: FC(F)Cl
Reactant: CCOC(=O)c1c(C)n(-c2ccc(OC)cc2)c2ccc(O)cc12
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [Br-]
Agent: [Na+]
Solvent: O
Solvent: ClCCl
Product: CCOC(=O)c1c(C)n(-c2ccc(OC)cc2)c2ccc(OC(F)F)cc12
Temperature: 0 °C
Reaction time: 2 h
Yield: 40 %

Procedure:
Freon-22 (HCF2Cl) gas is bubbled into a solution of ethyl 5-hydroxy-1-(4-methoxyphenyl)-2-methyl-1H-indole-3-carboxylate (250 mg, 0.77 mmol) in CH2Cl2 (5 mL) at 0° C. containing a small amount of tetrabutylammonium bromide as a phase transfer catalyst. A 50% solution of NaOH is added dropwise at 0° C. After the addition, the mixture is stirred at 0° C. for 2 h. After the addition of H2O, the organic phase is separated and washed with brine and dried over Na2SO4. The solvent is then concentrated and the residue is purified by column chromatography over silica gel using EtOAc/petroleum ether (1/2) as eluent to yield the desired product in 40% yield.
Reaction SMILES: Br[CH2:2][C:3]([NH:5][C:6]1[CH:11]=[C:10]([O:12][C:13]([F:16])([F:15])[F:14])[CH:9]=[CH:8][C:7]=1[OH:17])=[O:4].C(=O)([O-])[O-].[K+].[K+].CC#N.O.FC(F)(F)C(O)=O>CN(C)C=O.C(OCC)(=O)C>[F:14][C:13]([F:16])([F:15])[O:12][C:10]1[CH:9]=[CH:8][C:7]2[O:17][CH2:2][C:3](=[O:4])[NH:5][C:6]=2[CH:11]=1
Reactant: O=C(CBr)Nc1cc(OC(F)(F)F)ccc1O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Solvent: CC#N
Product: O=C1COc2ccc(OC(F)(F)F)cc2N1
Temperature: 85 °C
Yield: 91.1 %

Procedure:
2-bromo-N-{2-hydroxy-5-[(trifluoromethyl)oxy]phenyl}acetamide (4.23 g, 13.5 mmol), was dissolved in 140 mL of anhydrous dimethylformamide under argon. Potassium carbonate was added and suspended in the solution at room temperature. The mixture was warmed to 85° C. and was refluxed for one hour. HPLC (Eclipse XDB-C18, 4.6×250 mm, 5 micron, 1-99% CH3CN/H2O with 0.1% trifluoroacetic acid) indicated that all of the starting material (Rt=6.5 min) was consumed and a new single peak formed (Rt=6.2 min). The mixture was allowed to cool to room temperature before it was diluted with 600 mL of ethyl acetate and washed with water (2×150 mL) and brine (2×150 mL). The organic phase was dried over Na2SO4, filtered and concentrated to give 6-[(trifluoromethyl)oxy]-2H-1,4-benzoxazin-3(4H)-one (2.86 g, 12.3 mmol, 91%) as a brown amorphous solid. MS (ES) m/e 233 [M+H]+.
Reaction SMILES: [CH:1]1([C:4]2[N:8]([C:9]3[CH:14]=[CH:13][CH:12]=[C:11]([O:15][C:16]([F:19])([F:18])[F:17])[CH:10]=3)[N:7]=[C:6]([C:20]3[CH:25]=[CH:24][N:23]=[CH:22][CH:21]=3)[C:5]=2[C:26]([OH:28])=O)[CH2:3][CH2:2]1.[N:29]1([CH:34]2[CH2:39][CH2:38][NH:37][CH2:36][CH2:35]2)[CH2:33][CH2:32][CH2:31][CH2:30]1>>[CH:1]1([C:4]2[N:8]([C:9]3[CH:14]=[CH:13][CH:12]=[C:11]([O:15][C:16]([F:18])([F:17])[F:19])[CH:10]=3)[N:7]=[C:6]([C:20]3[CH:21]=[CH:22][N:23]=[CH:24][CH:25]=3)[C:5]=2[C:26]([N:37]2[CH2:38][CH2:39][CH:34]([N:29]3[CH2:33][CH2:32][CH2:31][CH2:30]3)[CH2:35][CH2:36]2)=[O:28])[CH2:2][CH2:3]1
Reactant: O=C(O)c1c(-c2ccncc2)nn(-c2cccc(OC(F)(F)F)c2)c1C1CC1
Reactant: C1CCN(C2CCNCC2)C1
Product: O=C(c1c(-c2ccncc2)nn(-c2cccc(OC(F)(F)F)c2)c1C1CC1)N1CCC(N2CCCC2)CC1
Yield: 91 %

Procedure:
In analogy to the procedure described in Example 160E], 5-cyclopropyl-3-pyridin-4-yl-1-(3-trifluoromethoxy-phenyl)-1H-pyrazole-4-carboxylic acid and 4-(1-pyrrolidinyl)piperidine gave the title compound as a light yellow gum (91%). MS: 526.0 (MH+).
Reaction SMILES: [CH2:1]([S:8]([NH:11][C:12](=[O:17])[C:13](OC)=[O:14])(=[O:10])=[O:9])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC(C)([O-])C.[K+]>CN(C)C=O>[OH:14][C:13]1[C:12](=[O:17])[NH:11][S:8](=[O:10])(=[O:9])[C:1]=1[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: COC(=O)C(=O)NS(=O)(=O)Cc1ccccc1
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: O=C1NS(=O)(=O)C(c2ccccc2)=C1O
Temperature: 0 °C
Reaction time: 8 h
Yield: 2.9 %

Procedure:
To a solution of methyl N-benzylsulfonyloxamate (2.0 g., 0.077 mol) in dimethyl formamide (15 ml.) was added in portions potassium tert-butoxide (1.74 g., 0.016 md). After stirring overnight, the solids were removed by filtration and washed with ether. The filtrate was evaporated to dryness. The solid residue, combined with the first fraction, was dissolved in a small volume of water. The aqueous solution was made strongly acidic by the addition of concentrated hydrochloric acid. After cooling at 0° C. for one hour, there was obtained on filtration the title compound (0.51 g.) m.p. 240°-251° C. (dec.). Anal. Calc'd. for C9H7NO4S: % C, 48.00; % H, 3.13; % N, 6.22. Found: % C, 48.00; % H, 3.12; % N, 6.45. When 4-chlorobenzylsulfonamide is employed as the starting material in Example 1 in place of benzylsulfonamide, and the procedures of Steps A and B are followed, there is obtained 5-(4-chlorophenyl)-4-hydroxy-3(2H)-isothiazolone-1,1-dioxide. Similarly, when 4-methylbenzylsulfonamide is employed as the starting material in Example 1, there is obtained 4-hydroxy-5-(4-methylphenyl)-3(2H)-isothiazolone-1,1-dioxide. When 3,4-dichlorobenzylsulfonamide is employed as the starting material in Example 1, there is obtained 5-(3,4-dichlorophenyl)-4-hydroxy-3(2H)-isothiazolone-1,1-dioxide. And when 3,5-diethylbenzylsulfonamide is employed as the starting material in Example 1, there is obtained 5-(3,5-diethylphenyl)-4-hydroxy-3(2H)-isothiazolone-1,1-dioxide.
Reaction SMILES: [NH2:1][CH:2]([C:4]1[CH:12]=[C:11]([C:13]([CH3:16])([CH3:15])[CH3:14])[CH:10]=[C:9]2[C:5]=1[CH2:6][CH2:7][C:8]2([CH3:18])[CH3:17])[CH3:3].[ClH:19].C[CH:21]([NH2:36])[C:22]1C=[CH:26][C:25](CCC2C=CC=CC=2)=[CH:24][CH:23]=1>>[ClH:19].[C:13]([C:11]1[CH:10]=[C:9]2[C:5]([CH2:6][CH2:7][C:8]2([CH3:17])[CH3:18])=[C:4]([CH:2]([N:1]=[C:21]2[CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][NH:36]2)[CH3:3])[CH:12]=1)([CH3:16])([CH3:15])[CH3:14]
Reactant: CC(N)c1cc(C(C)(C)C)cc2c1CCC2(C)C
Reactant: CC(N)c1ccc(CCc2ccccc2)cc1
Agent: Cl
Product: CC(N=C1CCCCCN1)c1cc(C(C)(C)C)cc2c1CCC2(C)C

Procedure:
Following essentially the same procedure described in Example IV above and substituting 4-(α-aminoethyl)1,1-dimethyl-6-tert.-butylindane for the α-methyl-ρ-phenethylbenzylamine hydrochloride above, results in the formation of 2-[1-(6-tert.-butyl-1,1-dimethyl-4-indanyl)ethylimino]hexahydro-1H-azepine hydrochloride, having a M.P. of 257°-8° C. (dec.)
Reaction SMILES: [CH3:1][CH:2]([CH3:14])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12]Br.[CH:15]1([P:21]([CH:24]2[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]2)([SH:23])=[S:22])[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]1>>[CH:15]1([P:21]([CH:24]2[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]2)([S:23][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH:2]([CH3:14])[CH3:1])=[S:22])[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20]1
Reactant: CC(C)CCCCCCCCCCBr
Reactant: S=P(S)(C1CCCCC1)C1CCCCC1
Product: CC(C)CCCCCCCCCCSP(=S)(C1CCCCC1)C1CCCCC1

Procedure:
11-Methyldodecyl bromide was reacted with the ammonium salt of dicyclohexylphosphinodithioic acid to obtain isotridecyl dicyclohexylphosphinodithioate, a viscous colorless liquid, which on testing lasted 750 hours longer than the control. The total number of hours required to reach failure was 2.6 times that of the control.
Reaction SMILES: [Cl-].[Na+].[C:3]([C:5]1[CH:6]=[C:7]([CH:31]=[CH:32][CH:33]=1)[O:8][C:9]1[CH:26]=[C:25]([C:27]([F:30])([F:29])[F:28])[CH:24]=[CH:23][C:10]=1[CH2:11][CH:12](C(OCC)=O)[C:13]([O:15]CC)=[O:14])#[N:4]>CS(C)=O.O>[C:3]([C:5]1[CH:6]=[C:7]([CH:31]=[CH:32][CH:33]=1)[O:8][C:9]1[CH:26]=[C:25]([C:27]([F:29])([F:30])[F:28])[CH:24]=[CH:23][C:10]=1[CH2:11][CH2:12][C:13]([OH:15])=[O:14])#[N:4]
Reactant: CCOC(=O)C(Cc1ccc(C(F)(F)F)cc1Oc1cccc(C#N)c1)C(=O)OCC
Agent: [Cl-]
Agent: [Na+]
Solvent: CS(C)=O
Solvent: O
Product: N#Cc1cccc(Oc2cc(C(F)(F)F)ccc2CCC(=O)O)c1
Temperature: 120 °C

Procedure:
Sodium chloride (0.1 g) was added to a solution of the product from step (iv) (0.6 g) in DMSO (5 ml) and water (1 ml) then heated at 120° C. for 12 hours. The mixture was cooled and partitioned between 2M sodium hydroxide and diethylether. The aqueous layer was acidified with 2M hydrochloric acid, extracted with ethyl acetate and the organic layer dried and evaporated under reduced pressure. The residue was purified by reverse phase HPLC. Yield 0.108 g.