Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][CH2:9][CH2:10][N:11]1[C:19]2[C:14](=[CH:15][CH:16]=[C:17]([C:20]([O:22][CH3:23])=[O:21])[CH:18]=2)[C:13]([CH:24]2[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]2)=[CH:12]1.C([O-])(=O)C.[K+].O>CN(C)C(=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH:24]1([C:13]2[C:14]3[CH:15]=[CH:16][C:17]([C:20]([O:22][CH3:23])=[O:21])=[CH:18][C:19]=3[N:11]3[CH2:10][CH2:9][CH2:8][C:3]4[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=4[C:12]=23)[CH2:25][CH2:26][CH2:27][CH2:28][CH2:29]1
Reactant: COC(=O)c1ccc2c(C3CCCCC3)cn(CCCc3ccccc3Br)c2c1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: CC(=O)[O-]
Agent: [K+]
Solvent: O
Solvent: CC(=O)N(C)C
Product: COC(=O)c1ccc2c(C3CCCCC3)c3n(c2c1)CCCc1ccccc1-3
Temperature: 160 °C
Reaction time: 5 h
Yield: 26.8 %

Procedure:
To a solution of methyl 1-[3-(2-bromophenyl)propyl]-3-cyclohexyl-1H-indole-6-carboxylate (250 mg, 0.550 mmol) in N,N-dimethylacetamide (7.5 ml) were added potassium acetate (59 mg, 0.605 mmol) and tetrakis(triphenylphosphine)palladium (32 mg, 0.0275 mmol), and the mixture was stirred at 160° C. for 5 hr. The reaction mixture was allowed to cool to room temperature. Water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed successively with water and saturated brine, and dried over anhydrous magnesium sulfate. After filtration, the solvent was evaporated under reduced pressure and the residue was purified by silica gel chromatography (hexane:ethyl acetate=8:1-4:1) to give methyl 13-cyclohexyl-6,7-dihydro-5H-benzo[3,4]azepino[1,2-a]indole-10-carboxylate (55 mg, yield 27%).
Reaction SMILES: Cl[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Cl:17])[C:7]=1[N:8]1[CH2:13][CH2:12][CH:11]([C:14]([NH2:16])=[O:15])[CH2:10][CH2:9]1.[CH3:18][N:19]1[CH:23]=[C:22](B2OC(C)(C)C(C)(C)O2)[CH:21]=[N:20]1.C(=O)([O-])[O-].[Na+].[Na+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(#N)C>[Cl:17][C:6]1[CH:5]=[N:4][CH:3]=[C:2]([C:22]2[CH:21]=[N:20][N:19]([CH3:18])[CH:23]=2)[C:7]=1[N:8]1[CH2:13][CH2:12][CH:11]([C:14]([NH2:16])=[O:15])[CH2:10][CH2:9]1
Reactant: NC(=O)C1CCN(c2c(Cl)cncc2Cl)CC1
Reactant: Cn1cc(B2OC(C)(C)C(C)(C)O2)cn1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CC#N
Product: Cn1cc(-c2cncc(Cl)c2N2CCC(C(N)=O)CC2)cn1
Yield: 28.4 %

Procedure:
General procedure D was followed using 1-(3,5-dichloropyridin-4-yl)piperidine-4-carboxamide 23 (24 mg, 0.088 mmol), 1-methyl-1H-pyrazole-4-boronic acid pinacol ester (20 mg, 0.11 mmol), tetrakis(triphenylphosphine)palladium(0) (5 mg, 5 mol %), acetonitrile (1 mL) and 0.5 M sodium carbonate (0.25 mL, 0.12 mmol) for 30 min. The crude product was purified by preparative tlc on silica gel (CH2Cl2, MeOH, 10:1) to furnish the title compound as a white solid (8 mg, 29%), LC-MS (ESI, 3.5 min) Rt 1.20 min, m/z 320 (100%, [M+H]+); m/z (ESI) C15H19ClN5O requires 320.1273 found [M+H]+ 320.1272.
Reaction SMILES: C(S(C1C=C(C2C=CC(O)=C3C=2C2C=C(C)C=NC=2N3)C=CC=1)(=O)=O)C.[CH2:27]([S:29]([C:32]1[CH:33]=[C:34]([C:38]2[CH:46]=[CH:45][C:44]([O:47][CH2:48][C@H:49]([OH:51])[CH3:50])=[C:43]3[C:39]=2[C:40]2[CH:55]=[C:54]([CH3:56])[CH:53]=[N:52][C:41]=2[NH:42]3)[CH:35]=[CH:36][CH:37]=1)(=[O:31])=[O:30])[CH3:28]>>[CH2:27]([S:29]([C:32]1[CH:33]=[C:34]([C:38]2[CH:46]=[CH:45][C:44]([O:47][CH2:48][C@@H:49]([OH:51])[CH3:50])=[C:43]3[C:39]=2[C:40]2[CH:55]=[C:54]([CH3:56])[CH:53]=[N:52][C:41]=2[NH:42]3)[CH:35]=[CH:36][CH:37]=1)(=[O:31])=[O:30])[CH3:28]
Reactant: CCS(=O)(=O)c1cccc(-c2ccc(OC[C@@H](C)O)c3[nH]c4ncc(C)cc4c23)c1
Agent: CCS(=O)(=O)c1cccc(-c2ccc(O)c3[nH]c4ncc(C)cc4c23)c1
Product: CCS(=O)(=O)c1cccc(-c2ccc(OC[C@H](C)O)c3[nH]c4ncc(C)cc4c23)c1

Procedure:
The title compound was prepared from Compound 157 using an analogous procedure to the procedure described for the preparation of Compound 233. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.17 (t, J=7.33 Hz, 3 H) 1.25 (d, J=6.06 Hz, 3 H) 2.27 (s, 3 H) 3.41 (q, J=7.33 Hz, 2 H) 3.94 (m, 1 H) 4.09-4.16 (m, 2 H) 4.97 (d, J=4.04 Hz, 1 H) 7.07-7.14 (m, 2 H) 7.57 (s, 1 H) 7.85 (t, J=7.71 Hz, 1 H) 7.96-8.00 (m, 2 H) 8.09 (s, 1 H) 8.28 (d, J=1.52 Hz, 1 H) 11.94 (s, 1 H); [M+H] calc'd for C23H25N2O4S, 425.2; found, 425.3.
Reaction SMILES: [C:1]([NH:8][CH2:9][CH:10]=[CH2:11])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].C([Li])(CC)C.N#N.[F:19][C:20]([F:34])([F:33])[C:21]1[CH:22]=[C:23]([CH:26]=[C:27]([C:29]([F:32])([F:31])[F:30])[CH:28]=1)[CH:24]=[O:25]>C1COCC1.[Cl-].[Cl-].[Zn+2]>[F:19][C:20]([F:33])([F:34])[C:21]1[CH:22]=[C:23]([CH:24]([OH:25])[CH:9]([NH:8][C:1](=[O:2])[O:3][C:4]([CH3:7])([CH3:6])[CH3:5])[CH:10]=[CH2:11])[CH:26]=[C:27]([C:29]([F:32])([F:30])[F:31])[CH:28]=1
Reactant: O=Cc1cc(C(F)(F)F)cc(C(F)(F)F)c1
Reactant: C=CCNC(=O)OC(C)(C)C
Agent: N#N
Agent: [Cl-]
Agent: [Li]C(C)CC
Solvent: C1CCOC1
Product: C=CC(NC(=O)OC(C)(C)C)C(O)c1cc(C(F)(F)F)cc(C(F)(F)F)c1
Temperature: -78 °C
Reaction time: 2 h
Yield: 44.9 %

Procedure:
To N-Boc-allylamine (50.0 g, 0.318 mol) in anhydrous THF (800 mL) at −78° C. was added sec-butyllithium (1.30 M in cyclohexane, 538.0 mL, 0.7 mol) dropwise under a stream of N2 gas. The resulting yellow solution was stirred at −78° C. for an additional 2 hours, after which time ZnCl2 (1.1 M in Et2O, 349.8 mL, 0.35 mol) was added. The solution was stirred for 1 hour before 3,5-bis-trifluoromethylbenzaldehyde (169.3 g, 0.700 mol) was added to the clear solution. The mixture was stirred at −78° C. for 1 hour before quenching with acetic acid (227 mL). The reaction was poured into ice water (2 L) and the organic layer was washed with aqueous saturated NaHCO3 (2 L×2) and brine (1 L), was dried (MgSO4), and concentrated. The crude material was recrystallized from petroleum ether (300 mL) to yield tert-butyl {1-[3,5-bis(trifluoromethyl)phenyl]-1-hydroxybut-3-en-2-yl}carbamate (57 g) as a white powder. In total this process yielded 2.8 kg of material. MS ESI calc'd. for C17H20F6NO3 [M+H]+ 400.1. found 400.0.
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([OH:8])[CH:5]=[CH:4][C:3]=1[C:9]([N:11]1[CH2:15][CH2:14][CH2:13][C@H:12]1[CH2:16][N:17]1[CH2:21][CH2:20][CH2:19][CH2:18]1)=[O:10].[CH3:22][S:23]([C:26]1[CH:33]=[CH:32][C:29]([CH2:30]Cl)=[CH:28][CH:27]=1)(=[O:25])=[O:24]>>[F:1][C:2]1[CH:7]=[C:6]([O:8][CH2:30][C:29]2[CH:28]=[CH:27][C:26]([S:23]([CH3:22])(=[O:25])=[O:24])=[CH:33][CH:32]=2)[CH:5]=[CH:4][C:3]=1[C:9]([N:11]1[CH2:15][CH2:14][CH2:13][C@H:12]1[CH2:16][N:17]1[CH2:21][CH2:20][CH2:19][CH2:18]1)=[O:10]
Reactant: O=C(c1ccc(O)cc1F)N1CCC[C@H]1CN1CCCC1
Reactant: CS(=O)(=O)c1ccc(CCl)cc1
Product: CS(=O)(=O)c1ccc(COc2ccc(C(=O)N3CCC[C@H]3CN3CCCC3)c(F)c2)cc1

Procedure:
The title compound is prepared in a manner substantially analogous to Procedure C from (2-Fluoro-4-hydroxy-phenyl)-(2-(S)-pyrrolidin-1-ylmethyl-pyrrolidin-1-yl)-methanone and 4-methylsulfonylbenzyl chloride. MS (ES+) 461.2
Reaction SMILES: [O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]1[C:7]2[NH:15][N:14]=[N:13][C:8]=2[N:9]=[C:10]([NH2:12])[N:11]=1.[CH3:16][O:17][C:18]1[CH:25]=[CH:24][C:23]([N+:26]([O-:28])=[O:27])=[CH:22][C:19]=1[CH2:20]Br>CN(C=O)C.O>[O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]1[C:7]2[N:15]=[N:14][N:13]([CH2:20][C:19]3[CH:22]=[C:23]([N+:26]([O-:28])=[O:27])[CH:24]=[CH:25][C:18]=3[O:17][CH3:16])[C:8]=2[N:9]=[C:10]([NH2:12])[N:11]=1
Reactant: COc1ccc([N+](=O)[O-])cc1CBr
Reactant: Nc1nc(-c2ccco2)c2[nH]nnc2n1
Solvent: O
Solvent: CN(C)C=O
Product: COc1ccc([N+](=O)[O-])cc1Cn1nnc2c(-c3ccco3)nc(N)nc21
Reaction time: 1 h
Yield: 25.3 %

Procedure:
A solution of 7-(2-furyl)-1H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine (606 mg, 3 mmol) in DMF (5 mL) at 0° C., was treated with CsCO3 (977 mg, 3 mmol), stirred for 1 h, treated with 2-methoxy-5-nitrobenzyl bromide (738 mg, 3 mmol) and stirred at room temperature for 1 h. The reaction mixture was diluted with water (10 mL), filtered and the resulting solid purified by chromatography [SiO2; EtOAc:Heptane (2:1)] to give the title compound (279 mg, 25%) as a yellow solid.
Reaction SMILES: [CH:1]([NH:4][CH2:5][CH2:6][OH:7])([CH3:3])[CH3:2].CC(C)([O-])C.[K+].F[C:15]1[CH:25]=[CH:24][C:23]([N+:26]([O-:28])=[O:27])=[CH:22][C:16]=1[NH:17][S:18]([CH3:21])(=[O:20])=[O:19].Cl>CN(C)C=O.O.C(OCC)(=O)C>[CH:1]([NH:4][CH2:5][CH2:6][O:7][C:15]1[CH:25]=[CH:24][C:23]([N+:26]([O-:28])=[O:27])=[CH:22][C:16]=1[NH:17][S:18]([CH3:21])(=[O:19])=[O:20])([CH3:3])[CH3:2]
Reactant: CS(=O)(=O)Nc1cc([N+](=O)[O-])ccc1F
Reactant: CC(C)NCCO
Agent: CC(C)(C)[O-]
Agent: Cl
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Solvent: CCOC(C)=O
Product: CC(C)NCCOc1ccc([N+](=O)[O-])cc1NS(C)(=O)=O
Temperature: 25 °C
Reaction time: 1 h
Yield: 88.4 %

Procedure:
2-(Isopropylamino)ethanol (24,0 g) solution in dimethylformamide (70 ml) was added with potassium tert-butoxide (21.9 g) in an ice bathing. After being stirred for 1 hour at room temperature, the reaction mixture was cooled down to 5° C. and added drop-wise with 2′-fluoro-5′-nitromethanesulfonanilide (21.8 g) in dimethylformamide (30 ml). After being stirred for 3 hours at room temperature, the reaction mixture was added into ethyl acetate (500 ml) and solids formed were collected by filtration and washed with ethyl acetate (100 ml). Solids obtained were dissolved into water (200 ml) and the solution was adjusted to pH=7 with 2N HCl . Resultant crystals were collected by filtration, washed with water, and dried under vacuum to obtain 2′-[2-(isopropylamino)ethoxy]-5′-nitromethanesulfonanilide (26.1 g) as white crystal.
Reaction SMILES: [C:1]([CH:6]1[C:11](=[O:12])[CH2:10][CH:9]([C:13]2[C:14](=[O:23])[NH:15][C:16]3[C:21]([CH:22]=2)=[CH:20][CH:19]=[CH:18][CH:17]=3)[CH2:8][C:7]1=[O:24])(=O)[CH2:2][CH2:3][CH3:4].[CH2:25]([O:27][NH2:28])[CH3:26]>CO>[CH2:25]([O:27][NH:28][C:1](=[C:6]1[C:11](=[O:12])[CH2:10][CH:9]([C:13]2[C:14](=[O:23])[NH:15][C:16]3[C:21]([CH:22]=2)=[CH:20][CH:19]=[CH:18][CH:17]=3)[CH2:8][C:7]1=[O:24])[CH2:2][CH2:3][CH3:4])[CH3:26]
Reactant: CCON
Reactant: CCCC(=O)C1C(=O)CC(c2cc3ccccc3[nH]c2=O)CC1=O
Solvent: CO
Product: CCCC(NOCC)=C1C(=O)CC(c2cc3ccccc3[nH]c2=O)CC1=O

Procedure:
10 parts by weight of 2-butyryl-5-(2-oxoquinol-3-yl)-cyclohexane-1,3-dione, 2.0 parts by weight of ethoxyamine and 100 parts of methanol were stirred for 8 hours at room temperature. The solvent was distilled off under reduced pressure, the residue was taken up in 200 parts of dichloromethane, and the solution was washed with 5% strength hydrochloric acid, dried over sodium sulfate and evaporated down under reduced pressure. 2-(1-Ethoxyaminobutylidene)-5-(2-oxoquinol-3-yl)-cyclohexane-1,3-dione of melting point 155°-157° C. was obtained (active ingredient No. 2).
Reaction SMILES: [O:1]1CCCO[CH:2]1[C:7]1[CH:14]=[CH:13][C:10]([C:11]#[N:12])=[CH:9][C:8]=1[S:15]([CH2:18][CH2:19][OH:20])(=[O:17])=[O:16].C1(C)C=CC(S([O-])(=O)=O)=CC=1.[NH+]1C=CC=CC=1.O>CC(C)=O.O>[OH:20][CH2:19][CH2:18][S:15]([C:8]1[CH:9]=[C:10]([CH:13]=[CH:14][C:7]=1[CH:2]=[O:1])[C:11]#[N:12])(=[O:17])=[O:16]
Reactant: N#Cc1ccc(C2OCCCO2)c(S(=O)(=O)CCO)c1
Agent: Cc1ccc(S(=O)(=O)[O-])cc1
Agent: c1cc[nH+]cc1
Solvent: O
Solvent: CC(C)=O
Product: N#Cc1ccc(C=O)c(S(=O)(=O)CCO)c1
Temperature: 160 °C
Reaction time: 0.08 h

Procedure:
In an Emrys microwave, 4-(1,3-dioxan-2-yl)-3-[(2-hydroxyethyl)sulfonyl]benzonitrile (1970 mg, 6.6 mmol) and pyridinium 4-toluenesulfonate (1249 mg, 4.97 mmol; 0.75 eq.) in acetone/water (1:1, 30 ml) were heated with stirring at 160° C. for 5 min. The reaction mixture was then added to water (200 ml) and extracted with ethyl acetate (8×50 ml). The combined organic phases were then washed with saturated sodium chloride solution (2×50 ml), dried over sodium sulfate, filtered and concentrated under reduced pressure. To increase the yield, the sodium chloride wash solution was reextracted with ethyl acetate. The title compound was obtained as a solid (1.57 g, 99% of theory).
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([CH:10]=[CH:11][CH:12]=1)[CH:7]=[N:8]O)([O-])=O.B(O)(O)O>[Ni].O1CCOCC1>[NH2:1][C:4]1[CH:5]=[C:6]([CH:10]=[CH:11][CH:12]=1)[CH2:7][NH2:8]
Reactant: O=[N+]([O-])c1cccc(C=NO)c1
Agent: [Ni]
Agent: OB(O)O
Solvent: C1COCCO1
Product: NCc1cccc(N)c1
Yield: 86.4 %

Procedure:
33.2 g (0.2 mol) of m-nitrobenzaldoxime obtained in Example 2, 3 g of Raney nickel, 30.9 g (0.5 mol) of boric acid and 150 ml of dioxane were charged into an autoclave and reaction was effected at 30° C. under a hydrogen pressure of 10 Kg/cm2 ·G for five hours while vigorously stirring. After completion of the reaction, the resulting mixture was filtered to remove the catalyst, concentrated under reduced pressure and thereafter, was subject to the same post-treatment as in Example 1. 21.1 g of m-aminobenzylamine of 99.96% in purity was obtained. Yield 86.3%; B.P. 131°-132° C./6 mmHg).
Reaction SMILES: [CH3:1][C:2]1[C:11]2[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=2[N:5]=[C:4]2[CH2:12][CH2:13][NH:14][CH2:15][CH2:16][C:3]=12.[N:17]#[C:18][NH2:19]>C(O)(=O)C.C(O)C>[C:18]([N:14]1[CH2:15][CH2:16][C:3]2[C:4](=[N:5][C:6]3[CH:7]=[CH:8][CH:9]=[CH:10][C:11]=3[C:2]=2[CH3:1])[CH2:12][CH2:13]1)(=[NH:17])[NH2:19]
Reactant: N#CN
Reactant: Cc1c2c(nc3ccccc13)CCNCC2
Solvent: CCO
Solvent: CC(=O)O
Product: Cc1c2c(nc3ccccc13)CCN(C(=N)N)CC2

Procedure:
5 gm (23.6 millimols) of 1,2,4,5-tetrahydro-11-methyl-3H-azepino[4,5-b]quinoline were dissolved in 2.7 ml of glacial acetic acid and 20 ml of ethanol, and the solution was stirred at room temperature with 1.12 gm (26.6 millimols) of cyanamide for 72 hours. Thereafter, the product which had crystallized out was dissolved in water and reprecipitated with sodium hydroxide. Yield: 0.6 gm, 10% of theory; m.p. 140° C.
Reaction SMILES: [OH:1][CH2:2][CH:3]1[CH2:8][CH2:7][CH:6]=[CH:5][CH2:4]1.[CH2:9]=[CH:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH3:21].C(OOC(C)(C)C)(C)(C)C.Cl.C1OC1C.C(=O)([O-])[O-].[Na+].[Na+].S(=O)(=O)=O.[OH-].[Na+]>>[CH2:21]([C:4]1[CH2:5][CH2:6][CH2:7][CH2:8][C:3]=1[CH2:2][OH:1])[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16][CH2:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][CH3:9]
Reactant: C=CCCCCCCCCCCC
Reactant: OCC1CC=CCC1
Agent: CC(C)(C)OOC(C)(C)C
Agent: CC1CO1
Agent: Cl
Product: CCCCCCCCCCCCCC1=C(CO)CCCC1
Temperature: 50 °C
Reaction time: 4 h

Procedure:
To prepare a desired anionic biodegradable detergent, 4-hydroxymethylcyclohexene which is prepared according to the method set forth in Example I above is treated in a similar manner by alkylating said substituted cyclohexene with 1-tridecene utilizing a catalyst comprising di-t-butyl peroxide and a promoter comprising concentrated hydrochloric acid in an autoclave under 30 atmospheres of nitrogen and a reaction temperature in the range of from 130° to 140° C. for a period of 1 hour. The n-tridecyl hydroxymethylcyclohexene which is prepared according to this method, after recovery from the reaction mixture, is alkoxylated by treatment with 3 moles of propylene oxide per mole of substituted cyclohexene, the alkoxylation step being effected in an autoclave in the presence of a catalytic amount of sodium carbonate, the autoclave being heated to a temperature of 50° C. and being maintained thereat for a period of 4 hours. Upon completion of the 4-hour period, the autoclave is allowed to return to room temperature, the excess pressure is discharged and the n-tridecyl hydroxypolypropoxymethylcyclohexene is recovered. This product is then placed in an autoclave provided with cooling means and a molar excess of sulfur trioxide is charged thereto. Upon completion of the addition of the sulfur trioxide, the mixture is again stirred for an additional period of 1 hour and neutralized by the addition of a sodium hydroxide solution, the addition of the sodium hydroxide accompanied by stirring and cooling of the reaction mixture during a 1 hour period. Upon completion of the addition of the sodium hydroxide and after an additional period of 1 hour during which the reaction mixture is continuously stirred, the desired product comprising the sodium sulfate ester of n-tridecyl hydroxypolypropoxymethylcyclohexene is separated and recovered.
Reaction SMILES: Cl[C:2]1[C:11]([CH:12]=[O:13])=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([CH3:14])[CH:8]=2)[N:3]=1.[CH2:15]([NH2:17])[CH3:16].Cl.C([O-])(O)=O.[Na+]>O1CCOCC1.C1COCC1>[CH2:15]([NH:17][C:2]1[C:11]([CH:12]=[O:13])=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([CH3:14])[CH:8]=2)[N:3]=1)[CH3:16]
Reactant: Cc1ccc2nc(Cl)c(C=O)cc2c1
Reactant: CCN
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: C1COCCO1
Solvent: C1CCOC1
Product: CCNc1nc2ccc(C)cc2cc1C=O
Temperature: 160 °C
Yield: 54 %

Procedure:
To a solution of 2-chloro-6-methylquinoline-3-carbaldehyde (1.0 g, 4.86 mmol) in dioxane (10 mL) in a 20 mL microwave vial was added ethylamine (4 mL, 70% in water) and the resulting mixture was heated at 160° C. under microwave irradiation for 45 min. After cooling to RT, the mixture was poured into a solution THF:1 N HCl=1:1 (25 mL) and stirred for 25 min at RT. The mixture was neutralized until pH=7 with a saturated solution of NaHCO3 and extracted with CH2Cl2 (50 mL). The organic layer was washed with H2O (3×30 mL), brine (30 mL), dried over Na2SO4, filtered and evaporated to give 2-(ethylamino)-6-methylquinoline-3-carbaldehyde RBO 35156 as a yellow solid (566 mg, 54% yield).
Reaction SMILES: [CH3:1][C:2]1[O:6][C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)=[N:4][C:3]=1[CH2:13][CH2:14][OH:15].[CH2:16]([O:23][C:24]1[CH:29]=[CH:28][C:27](O)=[CH:26][CH:25]=1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O.N#N>C1COCC1>[CH2:16]([O:23][C:24]1[CH:29]=[CH:28][C:27]([O:15][CH2:14][CH2:13][C:3]2[N:4]=[C:5]([C:7]3[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=3)[O:6][C:2]=2[CH3:1])=[CH:26][CH:25]=1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1
Reactant: Oc1ccc(OCc2ccccc2)cc1
Reactant: Cc1oc(-c2ccccc2)nc1CCO
Agent: CC(C)OC(=O)N=NC(=O)OC(C)C
Agent: N#N
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: Cc1oc(-c2ccccc2)nc1CCOc1ccc(OCc2ccccc2)cc1
Yield: 75.7 %

Procedure:
2-(5-Methyl-2-phenyloxazol-4-yl)ethanol [Hulin, et al., J. Med. Chem. (1992) 35(10), 1853-64] (7.42 g, 36.0 mmol), 4-benzyloxyphenol (7.3 g, 36.0 mmol) and triphenylphosphine (9.57 g, 36.0 mmol) were dissolved in anhydrous THF (500 mL) and treated with dropwise addition of diisopropyl azodicarboxylate (7.18 mL, 36.0 mmol). The reaction mixture was stirred at 20° C. for 18 h under a positive-pressure atmosphere of N2. The reaction was partitioned between EtOAc (100 mL) and 0.1 N NaOH (100 mL), and the organic phase washed with water (100 mL) and brine (100 mL). The organic layer was dried with Na2SO4 and concentrated to a residue which was purified by gradient column chromatography (silica column, 100% hexanes to 20% EtOAc/hexanes) to provide a white solid (10.5 g, 76%). Rf=0.3 (10% EtOAc/hexanes) 1H NMR (250 MHz, DMSO-d6) δ 7.86 (d, 2H), 7.41-7.48 (m, 3H), 7.22-7.38 (m, 5H), 6.86 (d, 2H), 6.80 (d, 2H), 4.97 (s, 2H), 4.07 (t, 2H), 2.84 (t, 2H), 2.30 (s, 3H).
Reaction SMILES: [H-].[Na+].[NH:3]1[CH2:8][CH2:7][O:6][CH2:5][CH2:4]1.Cl.Cl[CH2:11][C:12]([NH2:14])=[NH:13]>C1COCC1>[O:6]1[CH2:7][CH2:8][N:3]([CH2:11][C:12]([NH2:14])=[NH:13])[CH2:4][CH2:5]1
Reactant: N=C(N)CCl
Reactant: C1COCCN1
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: N=C(N)CN1CCOCC1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
Sodium hydride (2.4 g, 60 mmol, 60%) was added to a solution of morpholine (5.2 g, 60 mmol) in THF (40 mL, anhydrous) and stirred for 30 min at room temperature under nitrogen. Chloroacetamidine hydrochloride (2.58 g, 20 mmol) was added to this solution in one portion and stirred at 50° C. overnight. Solvent was removed under reduced pressure and the dark brown oily residue was directly used in the next step.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[S:8]([NH2:11])(=[O:10])=[O:9].C(N(CC)CC)C.Cl[C:20]([O:22][CH3:23])=[O:21]>C(#N)C>[CH3:23][O:22][C:20](=[O:21])[NH:11][S:8]([C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1[Cl:1])(=[O:10])=[O:9]
Reactant: COC(=O)Cl
Reactant: NS(=O)(=O)c1ccccc1Cl
Solvent: CC#N
Solvent: CCN(CC)CC
Product: COC(=O)NS(=O)(=O)c1ccccc1Cl
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To 25.0 g 2-chloro-benzenesulfonamide was added 75 mL acetonitrile and 45.2 mL (2.5 eq) triethylamine. The mixture was cooled with an ice bath and 15.1 mL methyl chloroformate was slowly added dropwise. The mixture was stirred overnight at room temperature and concentrated in vacuo. Water was added and de aqueous layer was washed two times with ether. Acidification of the aqueous layer with 2 M HCl led to formation of a white precipitate. The suspension was filtered, the residue was washed with H2O and dried in vacuo to yield 19.1 g of a white solid. 1H NMR (400 MHz, DMSO-d6) δ 3.58 (s, 3H), 7.52-7.61 (m, 1H), 7.62-7.72 (m, 2H), 8.10 (dd, J=8 and 1.5 Hz, 1H), 12.42 (br s, 1H).
Reaction SMILES: [H-].[Na+].[CH2:3]([N:6]1[C:14]2[N:13]=[CH:12][NH:11][C:10]=2[C:9](=[S:15])[NH:8][C:7]1=[O:16])[CH2:4][CH3:5].CI.[CH2:19](O)C>CCCCCC>[CH3:19][S:15][C:9]1[C:10]2[NH:11][CH:12]=[N:13][C:14]=2[N:6]([CH2:3][CH2:4][CH3:5])[C:7](=[O:16])[N:8]=1
Reactant: CCCn1c(=O)[nH]c(=S)c2[nH]cnc21
Reactant: CCO
Agent: [H-]
Agent: [Na+]
Solvent: CI
Solvent: CCCCCC
Product: CCCn1c(=O)nc(SC)c2[nH]cnc21
Reaction time: 0.5 h

Procedure:
Under an argon atmosphere, 9.77 g (244 mmol) of 60% sodium hydride was washed 3 times with n-hexane. The solvent was evaporated under reduced pressure to dry. To the residue was added 900 ml of dimethylformamide. Under ice cooling, 57.0 g (271 mmol) of 3-n-propyl-6-thioxanthine (Japanese Published Unexamined Patent Application No. 183287/86) was gently added to the mixture. 15 minutes after, 15.2 ml (244 mmol) of methyl iodide was dropwise added to the reaction solution. After stirring was continued for 30 minutes, 50 ml of ethanol was added and the mixture was concentrated under reduced pressure. After 400 ml of water was added to the residue, the precipitate was collected by filtration to afford 13.9 g (yield, 23%) of Compound b as a light yellow powder. The filtrate was extracted 5 times with 200 ml of chloroform. After washing with saturated sodium chloride aqueous solution, the filtrate was dried over anhydrous sodium sulfate and the solvent was evaporated under reduced pressure. The residue was isolated and purified by silica gel column chromatography (eluting solvent; 10% methanol/chloroform) to afford further 16.0 g (yield, 26%) of Compound b as a light yellow powder.