Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[CH2:2][C:3]1[CH:7]=[C:6]([Cl:8])[S:5][C:4]=1[Cl:9].[CH3:10][C:11]1[N:16]=[C:15]([SH:17])[N:14]=[C:13]([OH:18])[CH:12]=1.C(N(CC)CC)C>C(O)C>[Cl:9][C:4]1[S:5][C:6]([Cl:8])=[CH:7][C:3]=1[CH2:2][S:17][C:15]1[N:14]=[C:13]([OH:18])[CH:12]=[C:11]([CH3:10])[N:16]=1
Reactant: Cc1cc(O)nc(S)n1
Reactant: Clc1cc(CBr)c(Cl)s1
Solvent: CCO
Solvent: CCN(CC)CC
Product: Cc1cc(O)nc(SCc2cc(Cl)sc2Cl)n1
Temperature: 25 °C
Reaction time: 8 h
Yield: 70.5 %

Procedure:
A mixture of 3-(bromomethyl)-2,5-dichlorothiophene (125 mg, 0.51 mmol), 6-methyl-2-sulfanylpyrimidin-4-ol (60 mg, 0.42 mmol), and triethylamine (180 μL, 1.3 mmol) in absolute ethanol (5 mL) was stirred at room temperature overnight. The mixture was recovered and evaporated. The solid residue was treated with water (100 mL). The solid product was recovered by filtration, washed with water (1×15 mL), diethyl ether (2×15 mL), and hexanes (2×15 mL), and then dried in vacuo, affording 2-{[(2,5-dichlorothiophen-3-yl)methyl]sulfanyl}-6-methylpyrimidin-4-ol (91 mg, 71% yield); 1H NMR (400 MHz, DMSO-d6): δ 2.21 (s, 3H), 4.27 (s, 2H), 6.02 (s (br), 1H), 7.17 (s 1H); M+308.
Reaction SMILES: [CH3:1][O:2][CH2:3][CH:4]([OH:6])[CH3:5].[CH2:7]([C:15]1[CH:20]=[CH:19][C:18]([C:21]2[CH:29]=[CH:28][C:24]([C:25](Cl)=[O:26])=[CH:23][CH:22]=2)=[CH:17][CH:16]=1)[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH3:14].C1(C)C=CC=CC=1>N1C=CC=CC=1>[CH3:1][O:2][CH2:3][CH:4]([O:6][C:25](=[O:26])[C:24]1[CH:23]=[CH:22][C:21]([C:18]2[CH:19]=[CH:20][C:15]([CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH3:14])=[CH:16][CH:17]=2)=[CH:29][CH:28]=1)[CH3:5]
Reactant: CCCCCCCCc1ccc(-c2ccc(C(=O)Cl)cc2)cc1
Reactant: COCC(C)O
Solvent: c1ccncc1
Solvent: Cc1ccccc1
Product: CCCCCCCCc1ccc(-c2ccc(C(=O)OC(C)COC)cc2)cc1

Procedure:
0.8 g of 1-methoxy-2-propanol, 3.2 g of p-(p-n-octylphenyl)-benzoic acid chloride 20 ml of toluene and 2.1 ml of pyridine are boiled under reflux for 6 hours. The pyridinium chloride is filtered off hot with suction and the filtrate is worked up in the customary manner. Optically active 1-methoxy-2-[p-(p-n-octylphenyl)-benzoyloxy]-propane is obtained
Reaction SMILES: [OH:1][C:2]1([C:12]#[C:13][C:14]([C:16]2[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=2)=O)[CH2:11][CH2:10][C:5]2([O:9][CH2:8][CH2:7][O:6]2)[CH2:4][CH2:3]1.Cl.[CH3:25][O:26][C:27]1[CH:32]=[CH:31][C:30]([NH:33][NH2:34])=[CH:29][CH:28]=1.C(N(CC)CC)C>C(O)C>[CH3:25][O:26][C:27]1[CH:32]=[CH:31][C:30]([N:33]2[C:14]([C:16]3[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=3)=[CH:13][C:12]([C:2]3([OH:1])[CH2:11][CH2:10][C:5]4([O:9][CH2:8][CH2:7][O:6]4)[CH2:4][CH2:3]3)=[N:34]2)=[CH:29][CH:28]=1
Reactant: COc1ccc(NN)cc1
Reactant: COc1ccc(C(=O)C#CC2(O)CCC3(CC2)OCCO3)cc1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: CCO
Product: COc1ccc(-c2cc(C3(O)CCC4(CC3)OCCO4)nn2-c2ccc(OC)cc2)cc1
Temperature: 25 °C
Reaction time: 20 h
Yield: 88.4 %

Procedure:
To a solution of 3-(8-hydroxy-1,4-dioxaspiro[4.5]decan-8-yl)-1-(4-methoxyphenyl)-2-propyn-1-one (Reference Example 17) (700 mg, 2.24 mmol) in ethanol (4.5 mL), a solution of 4-methoxyphenylhydrazine hydrochloride (470 mg, 2.69 mmol) and triethylamine (0.74 mL, 5.41 mmol) in ethanol (4.5 mL) was added, and the obtained solution was stirred at room temperature for 20 hours. The reaction solution was concentrated under reduced pressure. Distilled water was added to the residue and the resultant was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by flash chromatography (silica gel, n-hexane/ethyl acetate) to obtain the captioned compound (864 mg, 1.98 mmol, 88%) as a white amorphous product.
Reaction SMILES: [NH2:1][C:2]1[CH:6]=[CH:5][O:4][C:3]=1[C:7](=[O:12])[C:8]([CH3:11])([CH3:10])[CH3:9].C(N(CC)CC)C.[Br:20][CH2:21][C:22](Br)=[O:23]>C(Cl)Cl.C(OCC)(=O)C.[Na+].[Cl-]>[Br:20][CH2:21][C:22]([NH:1][C:2]1[CH:6]=[CH:5][O:4][C:3]=1[C:7](=[O:12])[C:8]([CH3:9])([CH3:11])[CH3:10])=[O:23]
Reactant: CC(C)(C)C(=O)c1occc1N
Reactant: O=C(Br)CBr
Agent: [Cl-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(C)(C)C(=O)c1occc1NC(=O)CBr
Temperature: 0 °C
Yield: 94.6 %

Procedure:
The 3-amino-2-pivaloylfuran (1.33 g, 8.0 mmol) was dissolved in methylene chloride (15 ml) under nitrogen and the solution was cooled to 0° C. Triethylamine (1.34 ml, 9.6 mmol) was added followed by 2-bromoacetyl bromide (1.94 g, 9.6 mmol) added dropwise over 1/4 hour. The mixture was stirred at ambient temperature over night. The reaction was diluted with ethyl acetate (25 ml) and saturated NaCl (10 ml). The organic layer was separated, washed with saturated NaCl, dried over Na2SO4, filtered and concentrated in vacuo. A brown oil (2.18 g) was obtained in theoretical yield.
Reaction SMILES: C(O)(=O)C.CC(O)C.[CH3:9][N:10]([CH3:23])[C:11]1[C:16]([N+:17]([O-])=O)=[C:15]([N:20]([CH3:22])[CH3:21])[N:14]=[CH:13][N:12]=1.C(=O)([O-])[O-].[K+].[K+]>O.[Fe].CC(C)=O>[NH2:17][C:16]1[C:11]([N:10]([CH3:23])[CH3:9])=[N:12][CH:13]=[N:14][C:15]=1[N:20]([CH3:21])[CH3:22]
Reactant: CN(C)c1ncnc(N(C)C)c1[N+](=O)[O-]
Agent: [Fe]
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)O
Solvent: CC(C)=O
Solvent: O
Product: CN(C)c1ncnc(N(C)C)c1N
Temperature: 80 °C
Reaction time: 1 h
Yield: 91.7 %

Procedure:
A mixture of 5 g of iron dust, 0.5 g of acetic acid and 3.5 ml of water was refluxed under heating for 30 minutes, allowed to cool at 80° C. and mixed with 14 ml of 2-propanol and gradually mixed with 4.22 g of 4, 6-bis (dimethylamino)-5-nitropyrimidine. The resultant mixture was stirred at the same temperature for 1 hour, allowed to cool at 40° C., mixed with a solution of 1.5 g of potassium carbonate in 2.5 ml of water and stirred for 1 hour. Acetone was added to the mixture, which was filtered through Celite. The filtrate was concentrated in vacuo, and the residue was mixed with water and shaken with ether. The organic layer was washed with water and saturated saline in order, dried over anhydrous sodium sulfate and the solvent evaporated to give 3.32 g of the titled compound.
Reaction SMILES: [CH2:1]([N:8]1[CH2:12][CH:11]([N+:13]([O-])=O)[CH:10]([C:16]2[CH:21]=[CH:20][C:19]([Cl:22])=[C:18]([F:23])[CH:17]=2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O.O.Cl[Sn]Cl.C([O-])(O)=O.[Na+]>CCOC(C)=O>[CH2:1]([N:8]1[CH2:9][CH:10]([C:16]2[CH:21]=[CH:20][C:19]([Cl:22])=[C:18]([F:23])[CH:17]=2)[CH:11]([NH2:13])[CH2:12]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=[N+]([O-])C1CN(Cc2ccccc2)CC1c1ccc(Cl)c(F)c1
Agent: Cl[Sn]Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: CCOC(C)=O
Product: NC1CN(Cc2ccccc2)CC1c1ccc(Cl)c(F)c1
Temperature: 25 °C
Yield: 64.8 %

Procedure:
To a stirred solution of (3SR,4RS)-1-benzyl-3-(4-chloro-3-fluoro-phenyl)-4-nitro-pyrrolidine (0.78 g, 2.33 mmol) in EtOAc (15 ml) was added portion wise SnCl2.2H2O (2.63 g, 11.6 mmol). The reaction mixture was then heated at reflux for 4 hours, cooled down to RT and a saturated aqueous solution of NaHCO3 (500 ml) was added. The salts were filtered off and the product extracted with EtOAc. The organic phases were then dried over Na2SO4, and concentration under vacuum. A column chromatography (CH2Cl2/MeOH 95/5) gave 0.46 g (65%) of the title compound as a light brown oil. ES-MS m/e: 305.1 (M+H+).
Reaction SMILES: [C:1]([N:10]1[CH2:27][CH2:26][C@@:17]23[C:18]4[CH:19]=[C:20]([OH:25])[CH:21]=[CH:22][C:23]=4[CH2:24][C@@H:11]1[C@@H:12]2[CH2:13][CH2:14][O:15][CH2:16]3)([O:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)=[O:2].[CH2:28](I)[CH3:29].C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[C:1]([N:10]1[CH2:27][CH2:26][C@@:17]23[C:18]4[CH:19]=[C:20]([O:25][CH2:28][CH3:29])[CH:21]=[CH:22][C:23]=4[CH2:24][C@@H:11]1[C@@H:12]2[CH2:13][CH2:14][O:15][CH2:16]3)([O:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)=[O:2]
Reactant: O=C(Oc1ccccc1)N1CC[C@]23COCC[C@H]2[C@H]1Cc1ccc(O)cc13
Reactant: CCI
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: CCOc1ccc2c(c1)[C@]13CCN(C(=O)Oc4ccccc4)[C@H](C2)[C@@H]1CCOC3

Procedure:
A mixture of XXVIII (0.005 m) from Step (c) above, ethyl iodide (0.01 m) and potassium carbonate (2 g) in 20 ml acetonitrile is heated at reflux for 18 hours. The mixture is filtered and the filtrate concentrated. The residue is treated with water and extracted with methylene chloride. The extracts are dried (MgSO4), filtered and concentrated to give the title compound.
Reaction SMILES: C([O:8][C:9]1[CH:10]=[C:11]([CH2:18][CH2:19][C:20]2[N:21]=[C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][N:23]3[C:28]=2[CH3:29])[CH:12]=[CH:13][C:14]=1[N+:15]([O-])=O)C1C=CC=CC=1>[Pd].CO.O1CCCC1>[NH2:15][C:14]1[CH:13]=[CH:12][C:11]([CH2:18][CH2:19][C:20]2[N:21]=[C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][N:23]3[C:28]=2[CH3:29])=[CH:10][C:9]=1[OH:8]
Reactant: Cc1c(CCc2ccc([N+](=O)[O-])c(OCc3ccccc3)c2)nc2ccccn12
Agent: [Pd]
Solvent: CO
Solvent: C1CCOC1
Product: Cc1c(CCc2ccc(N)c(O)c2)nc2ccccn12
Reaction time: 3 h
Yield: 30.5 %

Procedure:
10% Palladium on carbon (3.0 g) was added to a mixture of 2-[2-(3-benzyloxy-4-nitrophenyl)ethyl]-3-methylimidazo[1,2-a]pyridine (6.5 g) in a mixture of methanol and tetrahydrofuran, and the mixture was subjected to catalytic reduction under. atmospheric pressure for 3 hours at ambient temperature. The catalyst was removed by filtration and the filtrate was evaporated in vacuo. The residue was purified by a column chromatography on silica gel, and eluted with a mixture of chloroform and methanol (9:1, V/V). The eluted fast fractions containing the desired product were collected and evaporated in vacuo to give 2-[2-(4-amino-3-hydroxyphenyl)ethyl]-3-methylimidazo[1,2-a]pyridine (1.37 g).
Reaction SMILES: [CH2:1](Cl)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:9]1([CH:15]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[NH:16][CH2:17][CH2:18][NH2:19])[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1>C(#N)C>[CH2:1]([N:19]([CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[CH2:18][CH2:17][NH:16][CH:15]([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: NCCNC(c1ccccc1)c1ccccc1
Reactant: ClCc1ccccc1
Solvent: CC#N
Product: c1ccc(CN(CCNC(c2ccccc2)c2ccccc2)Cc2ccccc2)cc1

Procedure:
A solution of 2.9 g of benzyl chloride in 25 ml of acetonitrile is added to 5.6 g of N-diphenylmethyl-ethylenediamine in 30 ml of boiling acetonitrile. The mixture is heated under reflux for 12 hours, concentrated and partitioned between diethyl ether and 10% sodium hydroxide solution. The organic phases are dried over sodium sulphate and concentrated by evaporation. The residue can be recrystallised from methanol or diisopropyl ether. N,N-dibenzyl-N'-diphenylmethyl-ethylenediamine having a melting point of 89°-91° C. is obtained.
Reaction SMILES: [CH3:1][N:2]([CH3:18])[S:3]([C:6]1[CH:7]=[CH:8][CH:9]=[C:10]2[C:15]=1[N:14]=[C:13]([CH3:16])[CH:12]=[C:11]2Cl)(=[O:5])=[O:4].[Cl:19][C:20]1[CH:21]=[C:22]([CH:25]=[CH:26][C:27]=1[Cl:28])[CH2:23][NH2:24]>CO>[CH3:1][N:2]([CH3:18])[S:3]([C:6]1[CH:7]=[CH:8][CH:9]=[C:10]2[C:15]=1[N:14]=[C:13]([CH3:16])[CH:12]=[C:11]2[NH:24][CH2:23][C:22]1[CH:25]=[CH:26][C:27]([Cl:28])=[C:20]([Cl:19])[CH:21]=1)(=[O:5])=[O:4]
Reactant: Cc1cc(Cl)c2cccc(S(=O)(=O)N(C)C)c2n1
Reactant: NCc1ccc(Cl)c(Cl)c1
Solvent: CO
Product: Cc1cc(NCc2ccc(Cl)c(Cl)c2)c2cccc(S(=O)(=O)N(C)C)c2n1
Yield: 12.6 %

Procedure:
4-Chloro-2-methylquinoline-8-sulfonic dimethylamide (80 mg, 0.281 mmole) and 3,4-dichlorobenzylamine (100 mg, 0.568 mmole) were stirred at 155° C. for 10 min in a microwave oven. Methanol was added and the mixture was concentrated, mixed with dichloromethane and then filtered. The residue was purified using silica gel chromatography, eluting with dichloromethane:methanol 95:5. Precipitation in ethyl acetate gave a pink solid (15 mg, 13%).
Reaction SMILES: [F:1][C:2]1[C:9]([CH:10]=[O:11])=[C:8]([F:12])[CH:7]=[CH:6][C:3]=1[C:4]#[N:5].[BH4-].[Na+].O>C(O)C>[F:1][C:2]1[C:9]([CH2:10][OH:11])=[C:8]([F:12])[CH:7]=[CH:6][C:3]=1[C:4]#[N:5]
Reactant: N#Cc1ccc(F)c(C=O)c1F
Agent: [BH4-]
Agent: [Na+]
Solvent: CCO
Solvent: O
Product: N#Cc1ccc(F)c(CO)c1F
Temperature: 0 °C
Reaction time: 1 h

Procedure:
A stirred solution of 300 mg (3.48 mmol) of 2,4-difluoro-3-formylbenzonitrile (CAS 149489-14-5) in 10 ml of ethanol at 0° C. was admixed with 34 mg (0.89 mmol) of sodium borohydride in portions. After stirring at 0° C. for 1 h, the reaction mixture was mixed with water and extracted three times with methyl tert-butyl ether. The combined organic extracts were washed with water and saturated aqueous sodium chloride solution, and dried with a phase separation cartridge. The solvent was drawn off to dryness under reduced pressure, which gave 280 mg (82% of theory) of the target compound.
Reaction SMILES: [N:1]#[N:2].Cl.C[O:5][C:6](=[O:31])[C@H:7]([CH2:24][CH2:25][CH2:26][NH:27][C:28](=[NH:30])[NH2:29])[NH:8][S:9]([C:12]1[CH:21]=[CH:20][C:19]2[C:14](=[CH:15][CH:16]=[C:17]([O:22][CH3:23])[CH:18]=2)[CH:13]=1)(=[O:11])=[O:10].C(OCC)C.[CH2:37]([NH2:41])[CH2:38][CH2:39][CH3:40]>C(O)(=O)C>[N:1]#[N:2].[C:6]([OH:31])(=[O:5])[CH3:7].[CH3:23][O:22][C:17]1[CH:18]=[C:19]2[C:14](=[CH:15][CH:16]=1)[CH:13]=[C:12]([S:9]([NH:8][C@H:7]([C:6]([NH:41][CH2:37][CH2:38][CH2:39][CH3:40])=[O:5])[CH2:24][CH2:25][CH2:26][NH:27][C:28](=[NH:30])[NH2:29])(=[O:11])=[O:10])[CH:21]=[CH:20]2
Reactant: COC(=O)[C@H](CCCNC(=N)N)NS(=O)(=O)c1ccc2cc(OC)ccc2c1
Reactant: CCCCN
Agent: Cl
Agent: N#N
Solvent: CC(=O)O
Solvent: CCOCC
Product: CCCCNC(=O)[C@H](CCCNC(=N)N)NS(=O)(=O)c1ccc2cc(OC)ccc2c1
Reaction time: 48 h
Yield: 74 %

Procedure:
A 1.0 gram amount of N2 -(6-methoxy-2-naphthalenesulfonyl)-L-arginine methyl ester hydrochloride was dissolved in 2 ml of butylamine with vigorous agitation. After the resulting solution was allowed to stand at room temperature for 2 days, the butylamine was removed in vacuo and the residual syrup was washed well with 5 ml of water to obtain a powdery product. And then this powder was dissolved in minimum volume of acetic acid. To this solution ethyl ether was added to precipitate the viscous oily product. Reprecipitation from ethanol-ethyl ether gave N2 -(6-methoxy-2-naphthalenesulfonyl)-N-butyl-L-argininamide acetate in a powder form in 74% yield.
Reaction SMILES: C([C@H]1COC(C2C=CC=C(C3OC[C@H](C(C)C)N=3)N=2)=N1)(C)C.[CH3:23][O:24][C:25]1[CH:30]=[CH:29][C:28]([C:31]([C:78]2[CH:83]=[CH:82][C:81]([O:84][CH3:85])=[CH:80][CH:79]=2)([C:72]2[CH:77]=[CH:76][CH:75]=[CH:74][CH:73]=2)[O:32][CH2:33][C@H:34]2[O:38][C@@H:37]([N:39]3[CH:69]=[CH:68][C:43]([NH:44][C:45]([C:60]4[CH:65]=[CH:64][C:63]([O:66][CH3:67])=[CH:62][CH:61]=4)([C:52]4[CH:57]=[CH:56][C:55]([O:58][CH3:59])=[CH:54][CH:53]=4)[C:46]4[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=4)=[N:42][C:40]3=[O:41])[C@H:36]([OH:70])[C@@H:35]2[OH:71])=[CH:27][CH:26]=1.[C:86]1([N:92]=[C:93]=[O:94])[CH:91]=[CH:90][CH:89]=[CH:88][CH:87]=1.COC1C=CC(C(C2C=CC(OC)=CC=2)(C2C=CC=CC=2)OC[C@H]2O[C@@H](N3C=CC(NC(C4C=CC(OC)=CC=4)(C4C=CC(OC)=CC=4)C4C=CC=CC=4)=NC3=O)[C@H](OC(=O)NC3C=CC=CC=3)[C@@H]2O)=CC=1>C(S([O-])(=O)=O)(F)(F)F.C(S([O-])(=O)=O)(F)(F)F.[Cu+2].O1CCOCC1>[CH3:23][O:24][C:25]1[CH:30]=[CH:29][C:28]([C:31]([C:78]2[CH:79]=[CH:80][C:81]([O:84][CH3:85])=[CH:82][CH:83]=2)([C:72]2[CH:73]=[CH:74][CH:75]=[CH:76][CH:77]=2)[O:32][CH2:33][C@H:34]2[O:38][C@@H:37]([N:39]3[CH:69]=[CH:68][C:43]([NH:44][C:45]([C:52]4[CH:57]=[CH:56][C:55]([O:58][CH3:59])=[CH:54][CH:53]=4)([C:60]4[CH:65]=[CH:64][C:63]([O:66][CH3:67])=[CH:62][CH:61]=4)[C:46]4[CH:47]=[CH:48][CH:49]=[CH:50][CH:51]=4)=[N:42][C:40]3=[O:41])[C@H:36]([OH:70])[C@@H:35]2[O:71][C:93](=[O:94])[NH:92][C:86]2[CH:91]=[CH:90][CH:89]=[CH:88][CH:87]=2)=[CH:27][CH:26]=1
Reactant: O=C=Nc1ccccc1
Reactant: COc1ccc(C(Nc2ccn([C@@H]3O[C@H](COC(c4ccccc4)(c4ccc(OC)cc4)c4ccc(OC)cc4)[C@@H](O)[C@H]3O)c(=O)n2)(c2ccccc2)c2ccc(OC)cc2)cc1
Agent: [Cu+2]
Agent: CC(C)[C@H]1COC(c2cccc(C3=N[C@@H](C(C)C)CO3)n2)=N1
Agent: COc1ccc(C(Nc2ccn([C@@H]3O[C@H](COC(c4ccccc4)(c4ccc(OC)cc4)c4ccc(OC)cc4)[C@@H](O)[C@H]3OC(=O)Nc3ccccc3)c(=O)n2)(c2ccccc2)c2ccc(OC)cc2)cc1
Solvent: C1COCCO1
Product: COc1ccc(C(Nc2ccn([C@@H]3O[C@H](COC(c4ccccc4)(c4ccc(OC)cc4)c4ccc(OC)cc4)[C@@H](OC(=O)Nc4ccccc4)[C@H]3O)c(=O)n2)(c2ccccc2)c2ccc(OC)cc2)cc1
Temperature: 25 °C
Reaction time: 1.25 h

Procedure:
The dioxane solution (4 ml) containing 2,6-bis[(4S)-isopropyl-2-oxazoline-2-yl]pyridine (0.02 mmol, 6.2 mg) and Cu(OTf)2 (II) (0.02 mmol, 7.4 mg) was stirred for 1.25 hours at room temperature. The dioxane solution (1 ml) of 5′-O-[bis(4-methoxyphenyl)phenylmethyl]-N4-[bis(4-methoxy-phenyl)phenylmethyl]cytidine (0.2 mmol, 169.6 mg) and the dioxane solution (1 ml) of phenyl isocyanate (0.2 mmol, 23.8 mg) were added thereto. After the mixture was continuously stirred for 4 hours at room temperature, the mixture was analyzed with high-performance liquid chromatography. As a result, it was found that 5′-O-[bis(4-methoxyphenyl)phenylmethyl]-N4-[bis(4-methoxy-phenyl)phenylmethyl]-2′-O-phenylcarbamoylcytidine and 5′-O-[bis(4-methoxyphenyl)phenylmethyl]-N4-[bis(4-methoxy-phenyl)phenylmethyl]-3′-O-phenylcarbamoylcytidine were produced at the ratio of 85:15, and the transformation ratio of the reaction was 93%.
Reaction SMILES: [ClH:1].[CH3:2][C:3]1[CH:4]=[C:5](/[CH:62]=[CH:63]/[CH2:64][CH2:65][N:66]2[CH2:71][CH2:70][CH2:69][C:68]3([CH2:76][CH2:75][N:74](C(OC(C)(C)C)=O)[CH2:73][CH2:72]3)[CH2:67]2)[CH:6]=[CH:7][C:8]=1[CH2:9][C:10]1[C:11]([O:18][C@@H:19]2[O:51][C@H:50]([CH2:52][O:53][C:54](=[O:61])[C:55]3[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=3)[C@@H:40]([O:41][C:42](=[O:49])[C:43]3[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=3)[C@H:30]([O:31][C:32](=[O:39])[C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)[C@H:20]2[O:21][C:22](=[O:29])[C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[N:12][NH:13][C:14]=1[CH:15]([CH3:17])[CH3:16]>ClCCl>[ClH:1].[ClH:1].[C:22]([O:21][C@@H:20]1[C@@H:30]([O:31][C:32](=[O:39])[C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[C@H:40]([O:41][C:42](=[O:49])[C:43]2[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=2)[C@@H:50]([CH2:52][O:53][C:54](=[O:61])[C:55]2[CH:56]=[CH:57][CH:58]=[CH:59][CH:60]=2)[O:51][C@H:19]1[O:18][C:11]1[C:10]([CH2:9][C:8]2[CH:7]=[CH:6][C:5](/[CH:62]=[CH:63]/[CH2:64][CH2:65][N:66]3[CH2:71][CH2:70][CH2:69][C:68]4([CH2:72][CH2:73][NH:74][CH2:75][CH2:76]4)[CH2:67]3)=[CH:4][C:3]=2[CH3:2])=[C:14]([CH:15]([CH3:17])[CH3:16])[NH:13][N:12]=1)(=[O:29])[C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1
Reactant: Cc1cc(/C=C/CCN2CCCC3(CCN(C(=O)OC(C)(C)C)CC3)C2)ccc1Cc1c(O[C@@H]2O[C@H](COC(=O)c3ccccc3)[C@@H](OC(=O)c3ccccc3)[C@H](OC(=O)c3ccccc3)[C@H]2OC(=O)c2ccccc2)n[nH]c1C(C)C
Agent: Cl
Solvent: ClCCl
Product: Cc1cc(/C=C/CCN2CCCC3(CCNCC3)C2)ccc1Cc1c(O[C@@H]2O[C@H](COC(=O)c3ccccc3)[C@@H](OC(=O)c3ccccc3)[C@H](OC(=O)c3ccccc3)[C@H]2OC(=O)c2ccccc2)n[nH]c1C(C)C
Reaction time: 18 h
Yield: 96 %

Procedure:
Add hydrogen chloride (4.0 M solution in 1,4-dioxane, 0.6 mL, 2.4 mmol) to a solution of tert-butyl 2-{(3E)-4-[3-methyl-4-({5-(propan-2-yl)-3-[(2,3,4,6-tetra-O-benzoyl-beta-D-glucopyranosyl)oxy]-1H-pyrazol-4-yl}methyl)phenyl]but-3-en-1-yl}-2,9-diazaspiro[5.5]undecane-9-carboxylate (275 mg, 0.25 mmol) in dichloromethane (5 mL). After overnight (18 hours) at room temperature, concentrate to remove the solvent under reduced pressure to yield the title compound as a solid (258 mg, 0.24 mmol). MS (m/z): 1015.6 (M+1).
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].[CH2:14]1[O:16][CH:15]1[CH2:17][OH:18]>>[OH:16][CH:15]([CH2:17][OH:18])[CH2:14][NH:13][CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12]
Reactant: OCC1CO1
Reactant: CCCCCCCCCCCCN
Product: CCCCCCCCCCCCNCC(O)CO
Reaction time: 8 h

Procedure:
Dodecylamine (25.02 g, 0.13 moles) was heated at 85° C., and glycidol (10 g, 0.13 moles) was added dropwise. The reaction was heated under nitrogen for 3 hours then allowed to stir overnight. A white solid was recovered (crude yield=33.27 g), and the solid was recrystallized in hot hexane to give pure neosphingosine (yield=10.86 g).
Reaction SMILES: [CH3:1][C:2]1([CH3:10])[CH2:8][C:7](=O)[O:6][C:4](=[O:5])[CH2:3]1.[H-].[Al+3].[Li+].[H-].[H-].[H-].O.[OH-].[Na+]>C1COCC1>[CH3:1][C:2]([CH3:10])([CH2:8][CH2:7][OH:6])[CH2:3][CH2:4][OH:5]
Reactant: CC1(C)CC(=O)OC(=O)C1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: O
Solvent: C1CCOC1
Product: CC(C)(CCO)CCO
Reaction time: 3 h

Procedure:
A solution of 3,3-dimethylglutaric anhydride in dry THF (60 cm3) was added over 30 min. to lithium aluminum hydride in dry THF (300 cm3) under nitrogen at 0° C. The mixture was then brought gradually up-to reflux. After 3 h, the mixture was cooled, treated with water (3.3 cm3), sodium hydroxide solution (15%, 3.3 cm3) and water (9.9 cm3). The mixture was then filtered, the precipitate extracted with EtOAc (×3), and the combined organics evaporated to afford 3,3-dimethyl-1,5-pentanediol (quantitative yield); 1H NMR (CDCl3) δ 0.95 (s, 6H), 1.57 (t, 4H, J=6.3 Hz), 3.75 (t, 4H, J=6.3 Hz).
Reaction SMILES: [C:1]1([O:7][CH3:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:9][O:10][C:11]1[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][C:12]=1[CH2:19][C:20](Cl)=[O:21].[Al+3].[Cl-].[Cl-].[Cl-]>ClC(Cl)C>[CH3:9][O:10][C:11]1[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][C:12]=1[CH2:19][C:20]([C:4]1[CH:5]=[CH:6][C:1]([O:7][CH3:8])=[CH:2][CH:3]=1)=[O:21]
Reactant: COc1ccc(OC)c(CC(=O)Cl)c1
Reactant: COc1ccccc1
Agent: [Al+3]
Agent: [Cl-]
Solvent: CC(Cl)Cl
Product: COc1ccc(C(=O)Cc2cc(OC)ccc2OC)cc1
Yield: 57.6 %

Procedure:
To a cooled solution (0° C.) of anisole (1.3 g, 12.4 mmol) and (2,5-Dimethoxyphenyl)acetyl chloride (2.2 g, 10.3 mmol) in dichloroethane (30 ml) was added AlCl3 (1.6 g, 12.4 mmol) and the reaction was stirred for thirty minutes. The reaction was then quenched with 2N HCl and the organic layer was then separated, dried, and concentrated. The resulting oil was taken up into MeOH and a solid crystallized which was collected by filtration to give a white solid (1.7 g, 58%): Mp=108–111° C.; 1H NMR (CDCl3) δ 8.01 (d, 2 H, J=9.0 Hz), 6.92 (d, 2 H, J=8.8 Hz), 6.80–6.70 (m, 3 H), 4.20 (s, 2 H), 3.86 (s, 3 H), 3.75 (s, 3 H), 3.74 (s, 3 H); MS 287 (M+H)+
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:31])[NH:10][C:11]2[CH:12]=[C:13]([C:17]3[CH:25]=[C:24]4[C:20]([C:21]([C:26](OCC)=[O:27])=[N:22][NH:23]4)=[CH:19][CH:18]=3)[CH:14]=[CH:15][CH:16]=2)=[CH:4][C:3]=1[C:32]([F:35])([F:34])[F:33].[BH4-].[Li+].C(=O)(O)[O-].[Na+].C(OCC)(=O)C>O1CCCC1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([NH:10][C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([C:17]3[CH:25]=[C:24]4[C:20]([C:21]([CH2:26][OH:27])=[N:22][NH:23]4)=[CH:19][CH:18]=3)[CH:12]=2)=[O:31])=[CH:4][C:3]=1[C:32]([F:34])([F:33])[F:35]
Reactant: CCOC(=O)c1n[nH]c2cc(-c3cccc(NC(=O)Nc4ccc(Cl)c(C(F)(F)F)c4)c3)ccc12
Agent: O=C([O-])O
Agent: [BH4-]
Agent: [Li+]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: O=C(Nc1cccc(-c2ccc3c(CO)n[nH]c3c2)c1)Nc1ccc(Cl)c(C(F)(F)F)c1
Temperature: 70 °C
Reaction time: 12 h
Yield: 47.5 %

Procedure:
To a stirred solution of ethyl 6-(3-(3-(4-chloro-3-(trifluoromethyl)phenyl)ureido)phenyl)-1H-indazole-3-carboxylate (73.7 mg) in tetrahydrofuran (5 Ml), was added lithium borohydride (0.44 Ml; LiBH4) at room temperature then, the mixture was stirred at 70° C. for 12 h. Saturated sodium bicarbonate solution and ethyl acetate were added. The aqueous layer was extracted with ethyl acetate and the combined organic layer was dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by flash column chromatography to give 1-(4-chloro-3-(trifluoromethyl)phenyl)-3-(3-(3-(hydroxymethyl)-1H-indazol-6-yl)phenyl)urea (32.1 mg).