Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[CH:27]=[CH:26][CH:25]=[CH:24][C:3]=1[C:4]([NH:6][CH2:7][CH2:8][N:9]1[CH2:14][CH2:13][CH:12]([C:15](=[O:23])[C:16]2[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=2)[CH2:11][CH2:10]1)=[O:5].C=O.[CH2:30](O)C>[OH-].[Na+].O>[F:22][C:19]1[CH:18]=[CH:17][C:16]([C:15]([CH:12]2[CH2:11][CH2:10][N:9]([CH2:8][CH2:7][N:6]3[C:4](=[O:5])[C:3]4[C:2](=[CH:27][CH:26]=[CH:25][CH:24]=4)[NH:1][CH2:30]3)[CH2:14][CH2:13]2)=[O:23])=[CH:21][CH:20]=1
Reactant: Nc1ccccc1C(=O)NCCN1CCC(C(=O)c2ccc(F)cc2)CC1
Reactant: CCO
Agent: C=O
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: O=C(c1ccc(F)cc1)C1CCN(CCN2CNc3ccccc3C2=O)CC1
Temperature: 25 °C
Yield: 50 %

Procedure:
A mixture of 6.5 parts of 2-amino-N-[2-[4-(4-fluorobenzoyl)-1-piperidinyl]ethyl]benzamide, 0.5 parts of paraformaldehyde, 3 drops of sodium hydroxide solution 50%, 80 parts of ethanol and 10 parts of water is stirred and refluxed overnight. The reaction mixture is allowed to cool to room temperature while stirring. The precipitated product if filtered off, washed with ethanol and crystallized from 200 parts of ethanol, yielding 3.3 parts (50%) of 3-[2-[4-(4-fluorobenzoyl)-1-piperidinyl]ethyl]-2,3-dihydro-4(1H)-quinazolinone; mp. 203.4° C.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C@H:11]([NH:14][C@@H](C2C=CC=CC=2)C)[C@@H:10]([CH3:23])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]>CO.[OH-].[Pd+2].[OH-]>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C@H:11]([NH2:14])[C@@H:10]([CH3:23])[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: C[C@@H](N[C@H]1CCN(C(=O)OC(C)(C)C)C[C@@H]1C)c1ccccc1
Agent: [Pd+2]
Agent: [OH-]
Solvent: CO
Product: C[C@H]1CN(C(=O)OC(C)(C)C)CC[C@@H]1N
Reaction time: 8 h

Procedure:
(3S, 4S)-3-Methyl-4-(1-(R)-phenyl-ethylamino)-piperidine-1-carboxylic acid tert-butyl ester (510 mg, 1.60 mmol) was dissolved in methanol (15 mL). Palladium hydroxide (20%, 100 mg) was added and the mixture was shaken under a hydrogen atmosphere overnight at 55 psi. The reaction was filtered and concentrated in vacuo to provide the title compound as a clear oil. Wt.: 320 mg (88%). NMR (300 MHz, CDCl3) δ4.06 (m, 1H), 3.96 (m, 1H), 2.73 (m, 1H), 2.34 (m, 2H), 1.77 (m, 1H), 1.43 (s, 9H), 1.27 (m, 2H), 0.94 (d, 3H); LC/MS m/z 215 (M+H)+.
Reaction SMILES: C([O:3][C:4]([C:6]1[NH:7][C:8]2[C:13]([CH:14]=1)=[CH:12][C:11]([C:15]1[CH:20]=[C:19]([Cl:21])[CH:18]=[C:17]([Cl:22])[CH:16]=1)=[CH:10][CH:9]=2)=[O:5])C.[CH:23]([O:26][C:27]1[CH:32]=[CH:31][C:30](B(O)O)=[CH:29][CH:28]=1)([CH3:25])[CH3:24]>>[Cl:22][C:17]1[CH:16]=[C:15]([C:11]2[CH:12]=[C:13]3[C:8](=[CH:9][CH:10]=2)[N:7]([C:30]2[CH:31]=[CH:32][C:27]([O:26][CH:23]([CH3:25])[CH3:24])=[CH:28][CH:29]=2)[C:6]([C:4]([OH:3])=[O:5])=[CH:14]3)[CH:20]=[C:19]([Cl:21])[CH:18]=1
Reactant: CC(C)Oc1ccc(B(O)O)cc1
Reactant: CCOC(=O)c1cc2cc(-c3cc(Cl)cc(Cl)c3)ccc2[nH]1
Product: CC(C)Oc1ccc(-n2c(C(=O)O)cc3cc(-c4cc(Cl)cc(Cl)c4)ccc32)cc1

Procedure:
The title compound was prepared in accordance with Example 8(c) from 5-(3,5-dichlorophenyl)-1H-indole-2-carboxylic acid ethyl ester (see step (a) above) and 4-isopropoxyphenylboronic acid, followed by ester hydrolysis in accordance with the procedure described in Example 35, Method 3, step (b).
Reaction SMILES: [C:1]1([SH:7])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(N(CC)CC)C.[F:15][C:16]([F:34])([F:33])[C:17]([N:19]([CH2:26][P:27]([O:31]Cl)([O:29]Cl)=[O:28])[CH2:20][C:21]([O:23][CH2:24][CH3:25])=[O:22])=[O:18].[CH:35]([NH2:38])([CH3:37])[CH3:36]>CCOCC>[F:15][C:16]([F:34])([F:33])[C:17]([N:19]([CH:26]([S:7][C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)[P:27]([OH:31])([O:29][NH:38][CH:35]([CH3:37])[CH3:36])=[O:28])[CH2:20][C:21]([O:23][CH2:24][CH3:25])=[O:22])=[O:18]
Reactant: CC(C)N
Reactant: CCOC(=O)CN(CP(=O)(OCl)OCl)C(=O)C(F)(F)F
Reactant: Sc1ccccc1
Solvent: CCOCC
Solvent: CCN(CC)CC
Product: CCOC(=O)CN(C(=O)C(F)(F)F)C(Sc1ccccc1)P(=O)(O)ONC(C)C
Temperature: 0 °C
Reaction time: 3 h
Yield: 13.4 %

Procedure:
A solution of thiophenol (2.9 ml, 0.0285 mole) and triethylamine (3.97 ml) in 50 ml. of ether was added to a solution of ethyl N-trifluoroacetyl-N-(dichlorophosphonomethyl)glycinate (9.9 g, 0.03 mole) in 150 ml. of ether at 0° C. After three hours, the solution was filtered and the cooled (0° C.) filtrate was treated with a solution of isopropylamine (4.85 ml, 0.057 mole) in 50 ml. of ether. After stirring overnight, the solution was filtered, washed with 1.5% aqueous hydrochloric acid, 1.5% ammonium hydroxide and saturated aqueous sodium chloride. Concentration in vacuo afforded an oil which was chromatographed on silica gel eluting with ethyl acetate-cyclohexane (1:1) to yield ethyl N-trifluoroacetyl-N-(phenylthio(isopropylamino)phosphonomethyl)glycinate (1.75 g) as a white solid, m.p. 102°-103° C.
Reaction SMILES: [F:1][C:2]1[CH:9]=[C:8]([N:10]2[CH2:15][CH2:14][O:13][CH2:12][CH2:11]2)[CH:7]=[CH:6][C:3]=1[C:4]#N.CC(C[AlH]CC(C)C)C.C1(C)C=CC=CC=1.[O:32]1CCCC1>>[F:1][C:2]1[CH:9]=[C:8]([N:10]2[CH2:15][CH2:14][O:13][CH2:12][CH2:11]2)[CH:7]=[CH:6][C:3]=1[CH:4]=[O:32]
Reactant: N#Cc1ccc(N2CCOCC2)cc1F
Reactant: C1CCOC1
Agent: CC(C)C[AlH]CC(C)C
Solvent: Cc1ccccc1
Product: O=Cc1ccc(N2CCOCC2)cc1F
Temperature: 25 °C
Reaction time: 23.5 h
Yield: 68 %

Procedure:
To a solution of 2-fluoro-4-(morpholino)-benzonitrile (2.82 g, 13.7 mmol) in tetrahydrofuran (27 ml) under a nitrogen atmosphere was added dropwise a 1.5 M solution of DIBAL-H in toluene (18.3 ml, 27.3 mmol) during 13 minutes and the resulting mixture stirred for 23.5 hr at room temperature. The mixture was cooled to −50° C. and the excess DIBAL-H destroyed by careful addition of methanol (27 ml). The mixture was then stirred at room temperature for 10 mins, saturated ammonium chloride (27 ml) added and the resulting mixture stirred at room temperature for 40 mins., and then evaporated under reduced pressure to a yellow solid. This solid was partitioned between dichloromethane (120 ml) and water (120 ml) and solid potassium carbonate added until the aqueous phase was pH 10. The phases were separate via a hydrophobic frit and the organic phase evaporated and the residue purified by a Biotage™ column (40 g, silica) eluting with cyclohexane:ethyl acetate: (7:3) to give 2-fluoro-4-(morpholino)-benzaldehyde (1.96 g, 68%) as a white solid.
Reaction SMILES: N([Si:4]([CH3:7])([CH3:6])[CH3:5])=[N+]=[N-].[CH:8]12[O:15][CH:9]1[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14]2.C([Br:19])C=C>ClC1C=CC=CC=1>[Br:19][C@@H:8]1[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][C@H:9]1[O:15][Si:4]([CH3:7])([CH3:6])[CH3:5]
Reactant: C[Si](C)(C)N=[N+]=[N-]
Reactant: C1CCC2OC2CC1
Reactant: C=CCBr
Solvent: Clc1ccccc1
Product: C[Si](C)(C)O[C@@H]1CCCCC[C@H]1Br
Yield: 82 %

Procedure:
To a vial containing 0.03 grams of (R)-catalyst prepared as in Example 1 was added a solution of azidotrimethylsilane (0.34 g, 2.95 mmol) and cycloheptene oxide (0.28 g, 2.50 mmol) in a mixture of allyl bromide (4.0 mL) and chlorobenzene (4.0 ml). After 48 h the volatiles were removed at reduced pressure and the residue was purified by flash chromatography on 220-400 mesh silica with 98% hexane and 2% ether as eluant. The product (1R,2R)-1-bromo-2-trimethylsiloxycycloheptane (0.54 g, 82%) was isolated by distillation of the solvent at reduced pressure. Anal. for C10H21OSiBr. Calcd: C, 45.28; H, 7.98; Br. 30.12; found: C, 45.26; H, 8.12; Br 30.55. 1H NMR: d 0.17 (s, 9 H), 1.45-1.89 (m, 8 H), 2.03 (M, 1 H), 2.28 (m, 1 H), 4.01 (m, 1 H), 4.12 (m, 1 H). 13C NMR: d 0.33, 21.62, 24.26, 27.49, 33.78, 34.13, 62.41, 78.90. [a]D25=−28.2, c=1.24 g/100 mL chloroform. Chiral capillary gas chromatographic analysis at 120° C. on Cyclodex B stationary phase indicated that the enantiomeric excess of the product was 80%.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[C:6]([CH:8]2[CH2:12][CH2:11][CH2:10][O:9]2)[C:5]([NH:13]C(=O)C(F)(F)F)=[C:4]([N+:20]([O-:22])=[O:21])[CH:3]=1.[OH-].[Na+]>O1CCOCC1.CC(OC)(C)C>[Br:1][C:2]1[CH:7]=[C:6]([CH:8]2[CH2:12][CH2:11][CH2:10][O:9]2)[C:5]([NH2:13])=[C:4]([N+:20]([O-:22])=[O:21])[CH:3]=1
Reactant: O=C(Nc1c(C2CCCO2)cc(Br)cc1[N+](=O)[O-])C(F)(F)F
Agent: [Na+]
Agent: [OH-]
Solvent: C1COCCO1
Solvent: COC(C)(C)C
Product: Nc1c(C2CCCO2)cc(Br)cc1[N+](=O)[O-]
Yield: 101.3 %

Procedure:
Dissolved N-(4-bromo-2-nitro-6-tetrahydrofuran-2-yl-phenyl)-2,2,2-trifluoro-acetamide (6) (54.00 g, 140.9 mmol) in 1,4-dioxane (162 mL) and added aqueous 6 M NaOH (70.45 mL, 422.7 mmol, JT-Baker 567202). The reaction mixture was stirred at reflux for 2 days (HPLC showed complete conversion), allowed to cool, diluted with MTBE (800 mL), washed with water (2×200 mL), saturated aqueous NH4Cl, water and brine. The mixture was dried over MgSO4, filtered, and concentrated under reduced pressure to give (6a) as a dark amber oil (40.96 g, 93% yield; overall 92% HPLC plus NMR purity). LCMS (C18 column eluting with 10-90% MeOH/water gradient from 3-5 minutes with formic acid modifier) M+1: 287.28 (3.44 min). 1H NMR (300 MHz, CDCl3) δ 8.24 (d, J=2.4 Hz, 1H), 7.41 (d, J2.3 Hz, 1H), 6.91 (s, 2H), 4.80 (t, J7.2 Hz, 1H), 4.14-4.05 (m, 1H), 3.98-3.90 (m, 1H), 2.36-2.19 (m, 1H), 2.15-2.01 (m, 3H) ppm.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[C:7](F)[C:6]([CH3:10])=[CH:5][C:4]=1[N+:11]([O-:13])=[O:12].[CH3:14][O:15][CH2:16][CH2:17][N:18]1[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]1.C([O-])([O-])=O.[K+].[K+].O>CS(C)=O>[CH3:10][C:6]1[CH:5]=[C:4]([N+:11]([O-:13])=[O:12])[C:3]([O:2][CH3:1])=[CH:8][C:7]=1[N:21]1[CH2:22][CH2:23][N:18]([CH2:17][CH2:16][O:15][CH3:14])[CH2:19][CH2:20]1
Reactant: COCCN1CCNCC1
Reactant: COc1cc(F)c(C)cc1[N+](=O)[O-]
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CS(C)=O
Product: COCCN1CCN(c2cc(OC)c([N+](=O)[O-])cc2C)CC1
Temperature: 130 °C
Yield: 86.1 %

Procedure:
To 1-fluoro-2-methyl-5-(methyloxy)-4-nitrobenzene (prepared according to Example 113, Step B) (1 g, 5.4 mmol) in 10 mL of DMSO was added, 1-[2-(methyloxy)ethyl]piperazine (1 g, 7 mmol), and K2CO3 (1.27 g, 4.2 mmol). The mixture was heated to 130° C. for 24 h. The mixture was then poured into 100 mL of H2O and extracted with EtOAc. The product was isolated by flash chromatography to give the title compound of step A (1.44 g, 4.65 mmol, 86%). 1H NMR (400 MHz, DMSO-d6) δ ppm 7.74 (s, 1H), 6.68 (s, 1H), 3.88 (s, 3H), 3.44 (t, J=5.68 Hz, 2H), 3.22 (s, 3H), 2.95-3.01 (m, 4H), 2.50-2.58 (m, 6H), 2.17 (s, 3H).
Reaction SMILES: [S:1]1[CH:5]=[CH:4][N:3]=[C:2]1[O:6][C:7]1[CH:14]=[CH:13][C:10]([CH2:11][OH:12])=[CH:9][CH:8]=1>CCCCCC.CCOC(C)=O>[S:1]1[CH:5]=[CH:4][N:3]=[C:2]1[O:6][C:7]1[CH:8]=[CH:9][C:10]([CH:11]=[O:12])=[CH:13][CH:14]=1
Reactant: OCc1ccc(Oc2nccs2)cc1
Solvent: CCCCCC
Solvent: CCOC(C)=O
Product: O=Cc1ccc(Oc2nccs2)cc1

Procedure:
Using the alcohol prepared above and the procedures described in Example 84E, except chromatography using 4:1 hexane-EtOAc was used for purification, provided 4-(thiazol-2-yloxy)benzaldehyde. 1H NMR (CDCl3) δ10.00 (s, 1H), 7.95 (m, 2H), 7.46 (m, 2H), 7.30 (d, 1H), 6.95 (d, 1H). MS (DCl/NH3) (M+H)+ 206 and (M+H+NH3)+ 223.
Reaction SMILES: [OH:1][C:2]1[CH2:7][C:6]([CH:15]([CH3:17])[CH3:16])([CH2:8][CH2:9][CH:10]2[CH2:14][CH2:13][CH2:12][O:11]2)[O:5][C:4](=[O:18])[CH:3]=1.[C:19]([C:23]1[CH:28]=[C:27]([CH2:29][OH:30])[C:26]([CH3:31])=[CH:25][C:24]=1[S:32]S(C1C=CC(C)=CC=1)(=O)=O)([CH3:22])([CH3:21])[CH3:20].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[C:19]([C:23]1[CH:28]=[C:27]([CH2:29][OH:30])[C:26]([CH3:31])=[CH:25][C:24]=1[S:32][C:3]1[C:4](=[O:18])[O:5][C:6]([CH:15]([CH3:16])[CH3:17])([CH2:8][CH2:9][CH:10]2[CH2:14][CH2:13][CH2:12][O:11]2)[CH2:7][C:2]=1[OH:1])([CH3:22])([CH3:21])[CH3:20]
Reactant: Cc1ccc(S(=O)(=O)Sc2cc(C)c(CO)cc2C(C)(C)C)cc1
Reactant: CC(C)C1(CCC2CCCO2)CC(O)=CC(=O)O1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: Cc1cc(SC2=C(O)CC(CCC3CCCO3)(C(C)C)OC2=O)c(C(C)(C)C)cc1CO

Procedure:
The title compound was prepared as described in General Method 16a using 4-hydroxy-6-isopropyl-6-[2-(tetrahydro-furan-2-yl)-ethyl]-5,6-dihydro-pyran-2-one (Example E-19; 0.98 mmol), toluene-4-thiosulfonic acid S-(2-tert-butyl-4-hydroxymethyl-5-methyl-phenyl)ester (Example BB-; 1.18 mmol), potassium carbonate (3.93 mmol) in DMF (5 mL). Flash chromatographed over silica gel using 10:90 EtOAc:CH2Cl2, mp 57-59° C. MS (APCI): 461 (M−H).
Reaction SMILES: C[O-].[Na+].[C:4]([O:11][CH3:12])(=[O:10])[CH2:5][C:6]([O:8][CH3:9])=[O:7].Br[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH3:19].O>CO>[CH2:14]([CH:5]([C:4]([O:11][CH3:12])=[O:10])[C:6]([O:8][CH3:9])=[O:7])[CH2:15][CH2:16][CH2:17][CH2:18][CH3:19]
Reactant: COC(=O)CC(=O)OC
Reactant: CCCCCCBr
Agent: C[O-]
Agent: [Na+]
Solvent: O
Solvent: CO
Product: CCCCCCC(C(=O)OC)C(=O)OC
Yield: 78.3 %

Procedure:
350.1 g of 30 percent sodium methylate solution in methanol were diluted with 550 ml of methanol under nitrogen and while stirring. 264.2 g of dimethyl malonate were added dropwise. After warming the suspension to 4020 321.0 g of 1-bromohexane were added dropwise. After stirring at 40° for 1 hour, under reflux for 2 hours, at 65°-69° for 2.5 hours and cooling the suspension to room temperature water was added and the mixture was stirred. The organic phase was separated. The aqueous phase was extracted with methylene chloride, the combined organic extracts were dried and filtered, the filter cake was washed with methylene chloride and the combined filtrates were concentrated. After distillation of the product there were obtained 329.3 g (78.3%) of dimethyl n-hexylmalonate.
Reaction SMILES: [CH2:1]([C:5]1[N:6]=[C:7]2[C:16]([N:17]([CH2:27][C:28]3[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[CH:30][CH:29]=3)[CH2:18][C:19]3[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=3)=[N:15][C:14]3[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=3)[N:8]2[CH:36]=1)[CH:2]([CH3:4])[CH3:3].C([Li])CCC.[O:42]1[C:44]([CH3:46])([CH3:45])[CH2:43]1>O1CCCC1>[CH3:26][O:25][C:22]1[CH:23]=[CH:24][C:19]([CH2:18][N:17]([CH2:27][C:28]2[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[CH:30][CH:29]=2)[C:16]2[C:7]3[N:8]([C:36]([CH2:43][C:44]([CH3:46])([OH:42])[CH3:45])=[C:5]([CH2:1][CH:2]([CH3:4])[CH3:3])[N:6]=3)[C:9]3[C:14]([N:15]=2)=[CH:13][CH:12]=[CH:11][CH:10]=3)=[CH:20][CH:21]=1
Reactant: CC1(C)CO1
Reactant: COc1ccc(CN(Cc2ccc(OC)cc2)c2nc3ccccc3n3cc(CC(C)C)nc23)cc1
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: COc1ccc(CN(Cc2ccc(OC)cc2)c2nc3ccccc3n3c(CC(C)(C)O)c(CC(C)C)nc23)cc1
Reaction time: 1 h
Yield: 22.6 %

Procedure:
To a solution of the 2-isobutyl-N,N-bis(4-methoxybenzyl)imidazo[1,2-a]quinoxalin-4-amine (134 mg, 0.28 mmol) (Example 1, D) in 2 mL of tetrahydrofuran was added n-butyl lithium (2.5M, 0.2 mL, 0.50 mmol) at −78° C. After being stirred at that temperature for 1 hour, 1,2-epoxy-2-methylpropane (72 mg, 1.0 mmol) was added. The reaction mixture was stirred at −78° C. for 2 hours, and then at room temperature for 4 hours. The reaction was quenched with 10 mL of saturated aqueous ammonium chloride. The resulting mixture was extracted with 100 mL of ethyl acetate. The organic layer was separated and washed with water (20 mL), brine (20 mL), dried over MgSO4, filtered and concentrated. The crude product was purified by flash column chromatography eluted with ethyl acetate and hexanes to give the titled compound (35 mg, 19%) and recovered starting material (100 mg, 63%). MS: MH+=553. 1H NMR (300 MHz, CDCl3): δ 8.41 (dd, 1H), 7.67 (dd, 1H), 7.20-7.37 (m, 6H), 6.84 (m, 4H), 5.31 (brs, 4H), 3.79 (s, 6H), 3.51 (s, 2H), 2.58 (d, 2H), 2.14 (m, 1H), 1.37 (s, 6H), 0.88 (d, 6H).
Reaction SMILES: [C:1](O[O:13][C:14](=[O:24])[CH2:15][CH2:16][CH2:17]CCCCCC)(=O)CCCCCCCCC.[CH2:25]([OH:27])[CH3:26]>>[C:14]1(=[O:24])[O:13][C:17](=[O:27])[CH:16]=[CH:15]1.[CH:25]([O:27][CH3:1])=[CH2:26]
Reactant: CCCCCCCCCC(=O)OOC(=O)CCCCCCCCC
Reactant: CCO
Product: C=COC
Product: O=C1C=CC(=O)O1

Procedure:
Zamora, U.S. Pat. No. 5,233,367, Example 1 (which used decanoyl peroxide as the polymerization initiator) was repeated to provide the ethyl half-ester copolymer of maleic anhydride and methyl vinyl ether as a 50% solution in ethanol. A hair spray composition was prepared at 55% VOC using this copolymer solution, and its properties were determined in comparative testing with similar hair spray compositions containing the copolymer solution of the invention.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[O:12][CH3:13])[NH:8][C:7](=[O:14])[CH:6]=[C:5]2[C:15]([F:18])([F:17])[F:16].[F-].[Cs+].[CH:21](I)([CH3:23])[CH3:22]>CN(C=O)C>[NH2:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[O:12][CH3:13])[N:8]=[C:7]([O:14][CH:21]([CH3:23])[CH3:22])[CH:6]=[C:5]2[C:15]([F:18])([F:16])[F:17]
Reactant: CC(C)I
Reactant: COc1cc2[nH]c(=O)cc(C(F)(F)F)c2cc1N
Agent: [Cs+]
Agent: [F-]
Solvent: CN(C)C=O
Product: COc1cc2nc(OC(C)C)cc(C(F)(F)F)c2cc1N
Yield: 54 %

Procedure:
This compound was prepared according to General Method 12 (EXAMPLE 22) from 6-amino-7-methoxy-4-(trifluoromethyl)-1H-quinolin-2-one (500 mg, 1.9 mmol), CsF (1.18 g, 7.7 mmol), isopropyl iodide (1.31 g, 7.7 mmol) in 8 mL DMF to afford 308 mg (53%) of 6-amino-2-isopropyloxy-7-methoxy-4-(trifluoromethyl)quinoline, a light yellow oil, and 190 mg (29%) of 2-isopropyloxy-7-methoxy-6N-(isopropyl)amino-4-(trifluoromethyl)quinoline, after flash chromatography (7:3 hexanes:EtOAc). Data for 6-amino-2-isopropyloxy-7-methoxy-4-(trifluoromethyl)quinoline: Rf 0.51 (4:1 hexanes:EtOAc); 1H NMR (500 MHz, CDCl3) δ 7.18 (s, 1H), 7.13 (broad s, 1H), 7.00 (s, 1H), 5.48 (hept, 1H, J=6.3), 4.11 (broad s, 2H), 4.01 (s, 3H), 1.40 (d, 6H, J=6.3).
Reaction SMILES: C(O)(=O)C.CCC(C)=O.[CH3:10][O:11][C:12]1[CH:17]=[C:16]([O:18][CH3:19])[N:15]=[C:14]([O:20][C:21]2[CH:26]=[CH:25][CH:24]=[C:23]([N+:27]([O-])=O)[C:22]=2[C:30]2[O:34][CH:33]=[N:32][CH:31]=2)[N:13]=1>[Ag].C(OCC)(=O)C>[NH2:27][C:23]1[CH:24]=[CH:25][CH:26]=[C:21]([O:20][C:14]2[N:15]=[C:16]([O:18][CH3:19])[CH:17]=[C:12]([O:11][CH3:10])[N:13]=2)[C:22]=1[C:30]1[O:34][CH:33]=[N:32][CH:31]=1
Reactant: COc1cc(OC)nc(Oc2cccc([N+](=O)[O-])c2-c2cnco2)n1
Agent: [Ag]
Solvent: CCC(C)=O
Solvent: CCOC(C)=O
Solvent: CC(=O)O
Product: COc1cc(OC)nc(Oc2cccc(N)c2-c2cnco2)n1
Temperature: 50 °C

Procedure:
0.24 g silver powder was suspended in 60% aqueous solution of acetic acid in a volume of 3.2 ml, and MEK solution of 0.6 g 5-[2-(4,6-dimethoxypyrimidine-2-yloxy)-6-nitrophenyl]oxazole was fed dropwise thereto at 50° C. while stirring, then the resulting solution was further stirred for 2 hours at 60-70° C. After completing the reaction, the solution reacted was added with ethyl acetate and was filtrated. The filtrate was washed with water and saturated saline solution in turn and was then dried by using anhydrous magnesium sulfate, and the solvent used was removed by distillation under reduced pressure. The residue obtained was purified by using silica gel column chromatography, affording the objective substance in an amount of 0.45 g.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:11]([CH3:17])[C:12](OCC)=[O:13])[C:5]2[O:9][CH:8]=[CH:7][C:6]=2[CH:10]=1.C([NH2:20])=O.C[O-].[Na+]>CN(C)C=O.C(OCC)(=O)C>[F:1][C:2]1[CH:3]=[C:4]([CH:11]([CH3:17])[C:12]([NH2:20])=[O:13])[C:5]2[O:9][CH:8]=[CH:7][C:6]=2[CH:10]=1
Reactant: CCOC(=O)C(C)c1cc(F)cc2ccoc12
Reactant: NC=O
Agent: C[O-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CC(C(N)=O)c1cc(F)cc2ccoc12
Temperature: 100 °C
Yield: 25 %

Procedure:
To a solution of 0.27 gm (1.15 mMol) ethyl 2-(5-fluorobenzofur-7-yl)propionate in 4 mL dimethylformamide were added sequentially 0.16 mL (3.91 mMol) freshly distilled formamide and 0.81 mL (0.80 mMol) sodium methoxide (1 M in methanol) dropwise and the resulting mixture was heated at 100° C. for 45 minutes. The reaction mixture was cooled to room temperature and was then diluted with 25 volumes of ethyl acetate. The mixture was then washed sequentially with water and saturated aqueous sodium chloride, and concentrated under reduced pressure. The residue was subjected to flash silica gel chromatography, eluting with 2:1 ethyl acetate:hexane. Fractions containing product were combined and concentrated under reduced pressure to provide 0.060 gm (25%) of the desired compound.
Reaction SMILES: [O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1/[C:6](=[N:24]/[O:25][CH3:26])/[C:7]([NH:9][C@@H:10]1[C:22](=[O:23])[N:12]2[C:13]([C:19]([OH:21])=[O:20])=[C:14]([CH2:17][OH:18])[CH2:15][S:16][C@H:11]12)=[O:8].[N-:27]=[C:28]=[O:29].C([O-])(O)=O.[Na+].CCOCC>O1CCOCC1>[CH3:26][O:25]/[N:24]=[C:6](\[C:7]([NH:9][C@@H:10]1[C:22](=[O:23])[N:12]2[C:13]([C:19]([OH:21])=[O:20])=[C:14]([CH2:17][O:18][C:28]([NH2:27])=[O:29])[CH2:15][S:16][C@H:11]12)=[O:8])/[C:2]1[O:1][CH:5]=[CH:4][CH:3]=1
Reactant: CO/N=C(\C(=O)N[C@@H]1C(=O)N2C(C(=O)O)=C(CO)CS[C@H]12)c1ccco1
Reactant: [N-]=C=O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCOCC
Solvent: C1COCCO1
Product: CO/N=C(\C(=O)N[C@@H]1C(=O)N2C(C(=O)O)=C(COC(N)=O)CS[C@H]12)c1ccco1
Reaction time: 0.12 h

Procedure:
A solution of (6R,7R)-7-[Z-2-(fur-2-yl)-2-methoxyiminoacetamido]-3-hydroxymethylceph-3-em-4carboxylic acid (3.8 g) in dioxan (35 ml) was added to the above isocyanate reagent in one portion and the resulting solution was stirred at ca 22° for 7 minutes. The reaction mixture was poured into 3% aqueous NaHCO3 solution (170 ml) and the pH was adjusted to 5 by the addition of more aqueous NaHCO3 solution. After heating to 40° for 2 hours and allowing to cool to 22° over 14 hours, the reaction mixture was washed (at pH 5.9) with ethyl acetate (2×200 ml), the aqueous layer was separated, layered with ethyl acetate (200 ml), and acidified with concentrated hydrochloric acid to pH 1.9. The organic layer was separated and the aqueous layer re-extracted with ethyl acetate (200 ml). The organic extracts were combined, washed with brine (2×400 ml), dried (MgSO4) and evaporated to give a white solid which, on trituration with ether (100 ml) afforded the title compound (3.18 g, 75% m.p. (MSO2) 175°; [α]D +42° (c 1.02, DMSO).
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][CH:4]([N:7]2[C:15]3[C:10](=[N:11][CH:12]=[CH:13][CH:14]=3)[NH:9][C:8]2=[O:16])[CH2:3][CH2:2]1.Cl[C:18]1[CH:23]=[C:22]([C:24]([C:26]2[CH:36]=[C:35]([CH3:37])[C:29]3[N:30]([CH3:34])[C:31](=[O:33])[O:32][C:28]=3[CH:27]=2)=[O:25])[C:21]([CH3:38])=[CH:20][N:19]=1>CN(C=O)C>[CH3:34][N:30]1[C:29]2[C:35]([CH3:37])=[CH:36][C:26]([C:24]([C:22]3[C:21]([CH3:38])=[CH:20][N:19]=[C:18]([N:1]4[CH2:2][CH2:3][CH:4]([N:7]5[C:15]6[C:10](=[N:11][CH:12]=[CH:13][CH:14]=6)[NH:9][C:8]5=[O:16])[CH2:5][CH2:6]4)[CH:23]=3)=[O:25])=[CH:27][C:28]=2[O:32][C:31]1=[O:33]
Reactant: O=c1[nH]c2ncccc2n1C1CCNCC1
Reactant: Cc1cnc(Cl)cc1C(=O)c1cc(C)c2c(c1)oc(=O)n2C
Solvent: CN(C)C=O
Product: Cc1cnc(N2CCC(n3c(=O)[nH]c4ncccc43)CC2)cc1C(=O)c1cc(C)c2c(c1)oc(=O)n2C
Temperature: 250 °C

Procedure:
0.26 g (1.2 mmol) 1-piperidin-4-yl-1,3-dihydroimidazo[4,5-b]pyridin-2-one and 0.13 g (0.40 mmol) 6-(2-chloro-5-methyl-pyridine-4-carbonyl)-3,4-dimethyl-3H-benzoxazol-2-one (mixture) were combined and heated to 250° C. for approx. 10 min. Then the mixture was dissolved in DMF and purified by preparative HPLC-MS. The fractions containing the product were combined and the organic solvent was evaporated down. The residue was neutralised with 1N aqueous sodium hydroxide solution, the precipitate formed was suction filtered, washed with water and dried.