Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C@@H:2]1[CH2:6][N:5]([C:7]2[N:15]=[C:14]3[C:10]([N:11]=[CH:12][N:13]3[CH:16]([CH3:18])[CH3:17])=[C:9]([NH:19][C:20]3[CH:21]=[N:22][N:23]([CH3:25])[CH:24]=3)[N:8]=2)[CH2:4][C@H:3]1[NH:26]C(=O)OCC1C=CC=CC=1.C([O-])=O.[NH4+].O>C(O)C>[NH2:26][C@H:3]1[C@H:2]([F:1])[CH2:6][N:5]([C:7]2[N:15]=[C:14]3[C:10]([N:11]=[CH:12][N:13]3[CH:16]([CH3:18])[CH3:17])=[C:9]([NH:19][C:20]3[CH:21]=[N:22][N:23]([CH3:25])[CH:24]=3)[N:8]=2)[CH2:4]1
Reactant: CC(C)n1cnc2c(Nc3cnn(C)c3)nc(N3C[C@@H](F)[C@H](NC(=O)OCc4ccccc4)C3)nc21
Agent: O=C[O-]
Agent: [NH4+]
Solvent: O
Solvent: CCO
Product: CC(C)n1cnc2c(Nc3cnn(C)c3)nc(N3C[C@@H](N)[C@H](F)C3)nc21
Yield: 94.6 %

Procedure:
A mixture of benzyl ((3R,4R)-4-fluoro-1-(9-isopropyl-6-((1-methyl-1H-pyrazol-4-yl)amino)-9H-purin-2-yl)pyrrolidin-3-yl)carbamate (390 mg, 0.8 mmol), ammonium formate (514 mg, 8 mmol) in ethanol (20 mL) was degassed for 3 min and 10%-Pd/C (50 mg) was then added. The reaction was stirred and heated to gentle reflux for 45 min. The catalyst was removed by filtration and washed well with ethanol (40 mL). The combined liquors were concentrated to give a residue, which was taken into water (5 mL) and extracted with DCM-isopropanol (9:1, 2×70 mL). The combined organic extracts were washed with saturated NaHCO3 (5 mL), dried over Na2SO4 and evaporated to give the title compound as a light yellow solid (272 mg, 96% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 9.58 (s, 1 H) 8.00 (s, 2 H) 7.90 (s, 2 H) 7.73 (s, 1 H) 4.89-5.08 (m, 1 H) 4.56-4.66 (m, 1 H) 3.86-4.00 (m, 1 H) 3.81-3.85 (m, 3 H) 3.58-3.80 (m, 3 H) 3.53 (d, J=11.13 Hz, 1 H) 1.51 (d, J=6.72 Hz, 6 H). 19F NMR (376 MHz, DMSO-d6) δ ppm −177.42 (s, 1F). m/z (APCI+) for C16H22FN9 360.2 (M+H)+. Chiral purity was determined as below (using racemic sample to compare):
Reaction SMILES: Br[CH:2]([CH:8](Br)[C:9]([C:11]1[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[C:13]([O:19][CH3:20])[CH:12]=1)=[O:10])[C:3]([O:5][CH2:6][CH3:7])=[O:4].COC1C=C(C(=O)C=CC(OCC)=O)C=CC=1OC.BrBr>C(Cl)Cl>[CH3:20][O:19][C:13]1[CH:12]=[C:11]([C:9](=[O:10])[C:8]#[C:2][C:3]([O:5][CH2:6][CH3:7])=[O:4])[CH:16]=[CH:15][C:14]=1[O:17][CH3:18]
Reactant: CCOC(=O)C(Br)C(Br)C(=O)c1ccc(OC)c(OC)c1
Agent: BrBr
Agent: CCOC(=O)C=CC(=O)c1ccc(OC)c(OC)c1
Solvent: ClCCl
Product: CCOC(=O)C#CC(=O)c1ccc(OC)c(OC)c1

Procedure:
The procedure as described above in connection with Intermediate 1 was repeated to prepare ethyl 2,3-dibromo-4-(3,4-dimethoxyphenyl)-4-oxobutanoate (7.3 g, 95%) in the form of a diastereo mixture as a colorless foam (mixing ratio=63:37) from, a solution of ethyl 4-(3,4-dimethoxyphenyl)-4-oxo-2-butenoate (4.8 g, 18 mmol) in methylene chloride (500 ml) and a solution of bromine (1.1 ml) in methylene chloride (100 ml). The diastereo mixture was used in the next reaction without separation.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11]2([CH2:21][CH:22]3[O:24]C3)[S:16](=[O:18])(=[O:17])[CH2:15][CH2:14][CH2:13][S:12]2(=[O:20])=[O:19])[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].[CH2:25](O)C.C(Cl)(Cl)Cl.[C:32]([OH:37])(=[O:36])[C:33]([OH:35])=[O:34]>CC(C)=O>[C:32]([OH:37])(=[O:36])[C:33]([OH:35])=[O:34].[CH3:25][CH:15]1[CH2:14][CH2:13][S:12](=[O:19])(=[O:20])[C:11]([C:5]2[CH:6]=[CH:7][C:8]([O:9][CH3:10])=[C:3]([O:2][CH3:1])[CH:4]=2)([CH2:21][CH2:22][OH:24])[S:16]1(=[O:17])=[O:18]
Reactant: COc1ccc(C2(CC3CO3)S(=O)(=O)CCCS2(=O)=O)cc1OC
Reactant: CCO
Agent: O=C(O)C(=O)O
Solvent: ClC(Cl)Cl
Solvent: CC(C)=O
Product: COc1ccc(C2(CCO)S(=O)(=O)CCC(C)S2(=O)=O)cc1OC

Procedure:
3.76 g of 2-(3,4-dimethoxyphenyl)-2-(2,3-epoxypropyl)-m-dithiane-1,1,3,3-tetraoxide are heated at reflux for 18 hours under argon with 50 ml of ethanol, 30 ml of chloroform and 1.95 g of N-methyl-homovetratrylamine. After evaporation of the solvent, the residue is chromatographed on silica gel with chloroform/ethanol (98:2). The oil obtained is dissolved in acetone and treated with an equivalent amount of anhydrous oxalic acid. The precipitate is filtered off and recrystallized from methanol/acetone. The racemic α- (3,4-dimethoxyphenethyl)-methylamino!-methyl-2-(3,4-dimethoxyphenyl)-m-dithiane-2-ethanol-1,1,3,3-tetraoxide oxalate (1:1) obtained crystallizes with 1 mol of acetone and melts at 162°-164° C.
Reaction SMILES: [OH-].[Na+].[Cl:3][C:4]1[CH:5]=[C:6]([CH:24]=[CH:25][C:26]=1[NH:27][C:28]([NH:30][CH3:31])=[O:29])[O:7][C:8]1[C:17]2[C:12](=[CH:13][C:14]([O:22][CH3:23])=[C:15]([C:18]([O:20]C)=[O:19])[CH:16]=2)[N:11]=[CH:10][CH:9]=1.Cl>CO>[Cl:3][C:4]1[CH:5]=[C:6]([CH:24]=[CH:25][C:26]=1[NH:27][C:28]([NH:30][CH3:31])=[O:29])[O:7][C:8]1[C:17]2[C:12](=[CH:13][C:14]([O:22][CH3:23])=[C:15]([C:18]([OH:20])=[O:19])[CH:16]=2)[N:11]=[CH:10][CH:9]=1
Reactant: CNC(=O)Nc1ccc(Oc2ccnc3cc(OC)c(C(=O)OC)cc23)cc1Cl
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: CNC(=O)Nc1ccc(Oc2ccnc3cc(OC)c(C(=O)O)cc23)cc1Cl
Temperature: 25 °C
Yield: 100 %

Procedure:
After adding methanol (14 ml) and a 2N sodium hydroxide aqueous solution (7 ml) to methyl 4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxylate (1.31 g, 3.15 mmol), the mixture was stirred at 60° C. for 30 minutes. The reaction solution was cooled to room temperature, 2N hydrochloric acid was added for neutralization, the methanol was distilled off, and the precipitated white crystals were filtered out, thoroughly washed with water and dried at 60° C. to obtain the title compound (1.26 g, 3.15 mmol, 100%).
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6](Cl)=[O:7])=[CH:4][C:3]=1[S:11](=[O:14])(=[O:13])[NH2:12].[CH3:15][C:16]1[C:17]2[CH:24]=[CH:23][CH:22]=[CH:21][C:18]=2[S:19][CH:20]=1.[Cl-].[Al+3].[Cl-].[Cl-]>ClC1C=CC=CC=1>[Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([C:20]2[S:19][C:18]3[CH:21]=[CH:22][CH:23]=[CH:24][C:17]=3[C:16]=2[CH3:15])=[O:7])=[CH:4][C:3]=1[S:11](=[O:14])(=[O:13])[NH2:12]
Reactant: Cc1csc2ccccc12
Reactant: NS(=O)(=O)c1cc(C(=O)Cl)ccc1Cl
Agent: [Al+3]
Agent: [Cl-]
Solvent: Clc1ccccc1
Product: Cc1c(C(=O)c2ccc(Cl)c(S(N)(=O)=O)c2)sc2ccccc12

Procedure:
is obtained as described in Example 1 from 2.5 g 4-chloro-3-sulfamoylbenzoyl chloride, 1.6 g 3-methylbenzo[b]thiophene and 3 g aluminum chloride in 50 ml chlorobenzene. Colorless crystals, m.p. 210° C.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8](=[O:15])[CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11].[H-].[Na+].[F:18][C:19]([F:29])([F:28])[C:20]1[CH:27]=[CH:26][C:23]([CH2:24]Br)=[CH:22][CH:21]=1.O>COCCOC>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8](=[O:15])[CH:9]([CH2:24][C:23]1[CH:22]=[CH:21][C:20]([C:19]([F:18])([F:28])[F:29])=[CH:27][CH:26]=1)[C:10]([O:12][CH2:13][CH3:14])=[O:11]
Reactant: FC(F)(F)c1ccc(CBr)cc1
Reactant: CCOC(=O)CC(=O)c1ccccc1F
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: COCCOC
Product: CCOC(=O)C(Cc1ccc(C(F)(F)F)cc1)C(=O)c1ccccc1F
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 73.4 %

Procedure:
To a solution of ethyl 3-(2-fluorophenyl)-3-oxopropionate (20 g, 95 mmol) in 1,2-dimethoxyethane (100 ml) was added sodium hydride (60% in oil, 3.80 g, 95 mmol) under ice-cooling and the mixture was stirred at room temperature for 30 min. To the reaction solution was dropwise added a solution of 4-trifluoromethylbenzyl bromide (22.7 g, 95 mmol) in 1,2-dimethoxyethane (50 ml) and the reaction solution was stirred at room temperature for 4 hrs. The reaction solution was poured into water (300 ml) and extracted with ethyl acetate (500 ml×2). The extract was washed with water and saturated brine, dried over anhydrous magnesium sulfate and evaporated under reduced pressure. The residue was purified by silica gel column chromatography (toluene:hexane=1:1-toluene) to give ethyl 3-(2-fluorophenyl)-3-oxo-2-((4-(trifluoromethyl)phenyl)methyl)propionate (25.7 g, 73%) as a colorless oil.
Reaction SMILES: Cl[CH2:2][CH2:3][C:4]([C:9]1[CH:14]=[CH:13][C:12]([F:15])=[CH:11][CH:10]=1)([OH:8])[CH2:5][CH:6]=[CH2:7].[CH3:16][N:17]([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[NH2:18]>[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[F:15][C:12]1[CH:13]=[CH:14][C:9]([C:4]([OH:8])([CH2:5][CH:6]=[CH2:7])[CH2:3][CH2:2][NH:18][N:17]([CH3:16])[C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[CH:10][CH:11]=1
Reactant: CN(N)c1ccccc1
Reactant: C=CCC(O)(CCCl)c1ccc(F)cc1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [I-]
Product: C=CCC(O)(CCNN(C)c1ccccc1)c1ccc(F)cc1
Temperature: 63 °C
Yield: 7.6 %

Procedure:
1-chloro-3-(4-fluorophenyl)hex-5-en-3-ol (58 mg, 0.25 mmol), 1-methyl-1-phenylhydrazine (500 mg, 4.09 mmol), and tetrabutylammonium iodide (92 mg, 0.25 mmol) were combined and heated in a microwave for 50 min at 63° C. The crude mixture was filtered and purified twice by chromatography on a silica gel cartridge eluted with an EtOAc/hexanes gradient to remove 1-methyl-1-phenylhydrazine. The residue was dissolved in Et2O and washed with 1 M aq HCl. The aqueous layer was treated with 1 M aq NaOH until a pH of 4 was reached, then extracted with Et2O. The organic layer was evaporated and the residue was further purified by preparative HPLC to provide 3-(4-fluorophenyl)-1-(2-methyl-2-phenylhydrazinyl)hex-5-en-3-ol (6 mg). LC-MS Method 1 m/z=315 (M+1).
Reaction SMILES: [CH2:1]([O:8][C:9]([CH2:11][C@H:12]([NH:15][C:16](=[O:22])[O:17][C:18]([CH3:21])([CH3:20])[CH3:19])[CH2:13][OH:14])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:23](C1C=C(C)C=C(C(C)(C)C)N=1)(C)(C)C.F[B-](F)(F)F.C[O+](C)C>ClCCl>[CH2:1]([O:8][C:9]([CH2:11][C@H:12]([NH:15][C:16](=[O:22])[O:17][C:18]([CH3:19])([CH3:21])[CH3:20])[CH2:13][O:14][CH3:23])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: Cc1cc(C(C)(C)C)nc(C(C)(C)C)c1
Reactant: CC(C)(C)OC(=O)N[C@H](CO)CC(=O)OCc1ccccc1
Agent: C[O+](C)C
Agent: F[B-](F)(F)F
Solvent: ClCCl
Product: COC[C@H](CC(=O)OCc1ccccc1)NC(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To tert-butyl (S)-1-((benzyloxy)carbonyl)-3-hydroxypropan-2-ylcarbamate (1 eq.) in dichloromethane was added 2,6-di-t-butyl 4-methylpyridine (2.5 eq.) and trimethyloxonium tetrafluoroborate (1.25 eq.) at 0° C. The reaction mixture was gradually warm to room temperature and stirred overnight. The reaction mixture was diluted with dichloromethane and washed with cold satd. sodium bicarbonate, water, and brine and dried over sodium sulfate. Purification by silica gel chromatography (25% EtOAc/Hexane) provide pure product as a colorless viscous liquid.
Reaction SMILES: [C:1]([O:5][C:6](=[O:22])[NH:7][C:8]1[CH:13]=[C:12]([N:14]([CH:16]([CH3:18])[CH3:17])[CH3:15])[C:11]([C:19]#[N:20])=[CH:10][C:9]=1[NH2:21])([CH3:4])([CH3:3])[CH3:2].C([O:27][C:28](=O)[CH2:29][C:30]([C:32]1[CH:37]=[CH:36][CH:35]=[C:34]([C:38]2[O:42][N:41]=[C:40]([CH3:43])[CH:39]=2)[CH:33]=1)=[O:31])(C)(C)C>>[C:1]([O:5][C:6](=[O:22])[NH:7][C:8]1[CH:13]=[C:12]([N:14]([CH:16]([CH3:17])[CH3:18])[CH3:15])[C:11]([C:19]#[N:20])=[CH:10][C:9]=1[NH:21][C:28](=[O:27])[CH2:29][C:30]([C:32]1[CH:37]=[CH:36][CH:35]=[C:34]([C:38]2[O:42][N:41]=[C:40]([CH3:43])[CH:39]=2)[CH:33]=1)=[O:31])([CH3:3])([CH3:4])[CH3:2]
Reactant: Cc1cc(-c2cccc(C(=O)CC(=O)OC(C)(C)C)c2)on1
Reactant: CC(C)N(C)c1cc(NC(=O)OC(C)(C)C)c(N)cc1C#N
Product: Cc1cc(-c2cccc(C(=O)CC(=O)Nc3cc(C#N)c(N(C)C(C)C)cc3NC(=O)OC(C)(C)C)c2)on1

Procedure:
The title compound was prepared from [2-amino-4-cyano-5-(isopropyl-methyl-amino)-phenyl]-carbamic acid tert-butyl ester (Example J31) (304 mg, 1.0 mmol) and 3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo-propionic acid tert-butyl ester (Example K4) (301 mg, 1.0 mmol) according to the general procedure M. Obtained as a light brown foam (380 mg, 71%).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:13][CH2:14][CH2:15][N:16]2[CH2:21][CH2:20][O:19][CH2:18][CH2:17]2)=[C:6]2[C:11]=1[NH:10][C:9](=O)[CH:8]=[CH:7]2.O=P(Cl)(Cl)[Cl:24].[Cl-].C([NH+](CC)CC)C>C(#N)C>[Cl:24][C:9]1[CH:8]=[CH:7][C:6]2[C:11](=[C:2]([Cl:1])[CH:3]=[CH:4][C:5]=2[O:13][CH2:14][CH2:15][N:16]2[CH2:21][CH2:20][O:19][CH2:18][CH2:17]2)[N:10]=1
Reactant: O=P(Cl)(Cl)Cl
Reactant: O=c1ccc2c(OCCN3CCOCC3)ccc(Cl)c2[nH]1
Agent: CC[NH+](CC)CC
Agent: [Cl-]
Solvent: CC#N
Product: Clc1ccc2c(OCCN3CCOCC3)ccc(Cl)c2n1
Temperature: 120 °C
Reaction time: 3 h
Yield: 119.2 %

Procedure:
8-chloro-5-(2-morpholinoethoxy)quinolin-2(1H)-one (200 mg, 0.6 mmol, 1 eq.) was placed in acetonitrile (1.7 mL) in the presence of POCl3 (301 μL, 3.2 mmol, 5 eq.) and triethylammonium chloride (738 mg, 3.2 mmol, 5 eq.). The reaction mixture was stirred at 120° C. for 3 hours. The mixture was then concentrated under reduced pressure and, after adding water to the residue (5 mL), was stirred at room temperature during 30 minutes. Then the resulting precipitate was washed with water and filtered to give 4-(2-((2,8-dichloroquinolin-5-yl)oxy)ethyl)morpholine (234 mg, 100%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[C:7]([C:9]2[CH:10]=[N:11][N:12]([CH3:14])[CH:13]=2)[CH:6]=[CH:5][C:4]=1[NH:15][CH:16]=O.[CH:18]1([CH2:21][O:22][C:23]2[C:28]3[N:29]=C(S(C)(=O)=O)[N:31]=[CH:32][C:27]=3[CH:26]=[CH:25][N:24]=2)[CH2:20][CH2:19]1>>[CH:18]1([CH2:21][O:22][C:23]2[C:28]3[N:29]=[C:16]([NH:15][C:4]4[CH:5]=[CH:6][C:7]([C:9]5[CH:10]=[N:11][N:12]([CH3:14])[CH:13]=5)=[CH:8][C:3]=4[O:2][CH3:1])[N:31]=[CH:32][C:27]=3[CH:26]=[CH:25][N:24]=2)[CH2:19][CH2:20]1
Reactant: COc1cc(-c2cnn(C)c2)ccc1NC=O
Reactant: CS(=O)(=O)c1ncc2ccnc(OCC3CC3)c2n1
Product: COc1cc(-c2cnn(C)c2)ccc1Nc1ncc2ccnc(OCC3CC3)c2n1
Yield: 52 %

Procedure:
The title compound was prepared according to Example 40 using N-(2-methoxy-4-(1-methyl-1H-pyrazol-4-yl)phenyl)formamide (Preparation 56) and 8-(cyclopropylmethoxy)-2-(methylsulfonyl)pyrido[3,4-d]pyrimidine (Preparation 69). The residue was purified by silica gel column chromatography eluting with 0 to 75% EtOAc in cyclohexane to give the title compound (27 mg, 52%).
Reaction SMILES: [CH:1]1([C:4]([NH:6][C:7]2[S:8][C:9]3[C:14]([N:15]=2)=[CH:13][CH:12]=[C:11]([O:16][C:17]2[CH:18]=[C:19]([CH:23]=[CH:24][CH:25]=2)C(O)=O)[N:10]=3)=[O:5])[CH2:3][CH2:2]1.C1(P([N:40]=[N+]=[N-])(C2C=CC=CC=2)=O)C=CC=CC=1.C(N(CC)CC)C.CN(C)C=O>O>[NH2:40][C:19]1[CH:18]=[C:17]([CH:25]=[CH:24][CH:23]=1)[O:16][C:11]1[N:10]=[C:9]2[S:8][C:7]([NH:6][C:4]([CH:1]3[CH2:2][CH2:3]3)=[O:5])=[N:15][C:14]2=[CH:13][CH:12]=1
Reactant: O=C(O)c1cccc(Oc2ccc3nc(NC(=O)C4CC4)sc3n2)c1
Reactant: [N-]=[N+]=NP(=O)(c1ccccc1)c1ccccc1
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Solvent: O
Product: Nc1cccc(Oc2ccc3nc(NC(=O)C4CC4)sc3n2)c1
Temperature: 25 °C
Reaction time: 3 h
Yield: 31.5 %

Procedure:
A mixture of 3-({2-[(cyclopropylcarbonyl)amino][1,3]thiazolo[5,4-b]pyridin-5-yl}oxy)benzoic acid (3.90 g, 11.0 mmol), diphenylphosphoryl azide (3.55 mL, 16.5 mmol), triethylamine (2.28 mL, 16.5 mmol) and N,N-dimethylformamide (80 mL) was stirred at room temperature for 3 hr, and water (20 mL) was added and the mixture was stirred at 100° C. for 15 hr. The precipitation solid was collected by filtration. 6N Hydrochloric acid (100 mL), ethyl acetate (30 mL) and tetrahydrofuran (10 mL) were added to the solid, and the mixture was stirred at room temperature for 30 min. The insoluble material was filtered off, and the aqueous layer was separated from the filtrate, neutralized with 8N aqueous sodium hydroxide solution, and extracted with ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate and filtrated. The filtrate was concentrated under reduced pressure, and the residue was collected by filtration and washed with ethyl acetate-hexane to give the title compound (1.13 g, 31%) as a white solid.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[NH:7][C:6](=[O:13])[C:5]2=[CH:14]OC.CN(C)C=O.[CH3:22][N:23]([CH3:28])[CH2:24][CH2:25][CH2:26][NH2:27]>CCOCC>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[NH:7][C:6](=[O:13])/[C:5]/2=[CH:14]\[NH:27][CH2:26][CH2:25][CH2:24][N:23]([CH3:28])[CH3:22]
Reactant: COC=C1C(=O)NC(=O)c2ccc(Br)cc21
Reactant: CN(C)CCCN
Solvent: CN(C)C=O
Solvent: CCOCC
Product: CN(C)CCCN/C=C1\C(=O)NC(=O)c2ccc(Br)cc21
Temperature: 25 °C
Reaction time: 1 h
Yield: 66 %

Procedure:
A mixture of 6-bromo-4-(methoxymethylene)-isoquinoline-1,3(2H,4H)-dione (70.5 mg, 0.25 mmole), dimethylformamide (2 mL) and N1,N1-dimethylpropane-1,3-diamine (25.6 mg, 0.25 mmole) is stirred at room temperature for one hour. The reaction mixture is diluted with ether, filtered and washed with fresh ether and dried to give a light brown solid, 65.8 mg, (66% yield) MS (ES+): 352.2, (M+H).
Reaction SMILES: [OH-].[Na+].O.C([O:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1/[CH:14]=[C:15](/[C:17]1[CH:26]=[CH:25][C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[N:18]=1)\[CH3:16])(=O)C.Cl>C(O)C>[N:18]1[C:19]2[C:24](=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH:25]=[CH:26][C:17]=1/[C:15](/[CH3:16])=[CH:14]/[C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=1[OH:7]
Reactant: CC(=O)Oc1ccccc1/C=C(\C)c1ccc2ccccc2n1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Product: C/C(=C\c1ccccc1O)c1ccc2ccccc2n1
Temperature: 100 °C
Yield: 70.8 %

Procedure:
Aqueous sodium hydroxide (5%, 8.8 g), followed by water (88 mL) were added to a stirred solution of (E)-2-(2-(quinolin-2-yl)prop-1-enyl)phenyl acetate (2.2 g, 7.3 mmol, 1.0 eq.) in ethanol (110 mL). The resulting mixture was heated at 100° C. for 10 min. The mixture was allowed to cool down a little and the pH was adjusted to 7.0 by careful addition of aqueous hydrochloric acid (10%). The mixture was allowed to cool down to r.t. and was then placed in a freezer (−18° C.) over night. The precipitation formed was isolated by filtration yielding the product (1.35 g, 71%) as a tan solid; 1H NMR (400 MHz, DMSO-d6) δ 2.38 (s, 3H, CH3), 6.87 (t, J=7.5 Hz, 1H, Ar), 6.92 (d, J=7.5 Hz, 1H, Ar), 7.16 (t, J=7.5 Hz, 1H, Ar), 7.36 (d, J=7.0 Hz, 1H, Ar), 7.56 (t, J=7.0 Hz, 1H, Ar), 7.61 (s, 1H, C═CH), 7.74 (t, J=7.0 Hz, 1H, Ar), 7.95 (d, J=8.5 Hz, 2H, Ar), 8.00 (d, J=8.5 Hz, 1H, Ar), 8.34 (d, J=8.5 Hz, 1H, Ar), 9.66 (br s, 1H, OH).
Reaction SMILES: [CH3:1][C:2]1[C@@H:19]([O:20]C([C@H](O)[C@@H](NC(C2C=CC=CC=2)=O)C2C=CC=CC=2)=O)[CH2:18][C@:14]2([OH:41])[C:15]([CH3:17])([CH3:16])[C:3]=1[C@@H:4]([O:59][C:60]([CH3:62])=[O:61])[C:5]([C@@:7]1([CH3:58])[C@H:12]([C@@H:13]2[O:42][C:43]([C:45]2[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=2)=[O:44])[C@:11]2([O:53][C:54]([CH3:56])=[O:55])[CH2:51][O:52][C@@H:10]2[CH2:9][C@H:8]1[OH:57])=[O:6].CC1[C@@H](OC([C@H](O)[C@@H](NC(C2C=CC=CC=2)=O)C2C=CC=CC=2)=O)C[C@]2(O)C(C)(C)C=1[C@@H](OC(C)=O)C([C@@]1(C)[C@H]([C@@H]2OC(C2C=CC=CC=2)=O)[C@]2(OC(C)=O)CO[C@@H]2C[C@@H]1O)=O>>[CH3:1][C:2]1[C@@H:19]([OH:20])[CH2:18][C@:14]2([OH:41])[C:15]([CH3:16])([CH3:17])[C:3]=1[C@@H:4]([O:59][C:60]([CH3:62])=[O:61])[C:5]([C@@:7]1([CH3:58])[C@H:12]([C@@H:13]2[O:42][C:43]([C:45]2[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=2)=[O:44])[C@:11]2([O:53][C:54]([CH3:56])=[O:55])[CH2:51][O:52][C@@H:10]2[CH2:9][C@@H:8]1[OH:57])=[O:6]
Reactant: CC(=O)O[C@H]1C(=O)[C@]2(C)[C@H](O)C[C@H]3OC[C@@]3(OC(C)=O)[C@H]2[C@H](OC(=O)c2ccccc2)[C@]2(O)C[C@H](OC(=O)[C@H](O)[C@@H](NC(=O)c3ccccc3)c3ccccc3)C(C)=C1C2(C)C
Agent: CC(=O)O[C@H]1C(=O)[C@@]2(C)[C@H]([C@H](OC(=O)c3ccccc3)[C@]3(O)C[C@H](OC(=O)[C@H](O)[C@@H](NC(=O)c4ccccc4)c4ccccc4)C(C)=C1C3(C)C)[C@]1(OC(C)=O)CO[C@@H]1C[C@@H]2O
Product: CC(=O)O[C@H]1C(=O)[C@@]2(C)[C@H]([C@H](OC(=O)c3ccccc3)[C@]3(O)C[C@H](O)C(C)=C1C3(C)C)[C@]1(OC(C)=O)CO[C@@H]1C[C@@H]2O

Procedure:
Degradation products were formed in the same proportions as in the experiments conducted under room temperature but in significantly lower quantities. Again, 7-epi-taxol was the main degradation product of paclitaxel. Its amounts formed during 32 h increased from about 3% at pH 7.0 to about 10% at pH 8.0 (see Table 11). Baccatin III and 10-deacethyltaxol were formed for about 5 to 6% at pH 8.0.
Reaction SMILES: BrC1C2N(N=C(Cl)N=2)C=CC=1.COC1C=CC(CN)=CC=1.[CH3:22][N:23]1[CH2:28][CH2:27][N:26]([C:29]2[CH:34]=[CH:33][C:32]([NH2:35])=[CH:31][CH:30]=2)[CH2:25][CH2:24]1.[Cl:36][C:37]1[N:55]=[C:40]2[C:41]([NH:45][CH2:46][C:47]3[CH:52]=[CH:51][C:50]([O:53][CH3:54])=[CH:49][CH:48]=3)=[CH:42][CH:43]=[CH:44][N:39]2[N:38]=1>>[Cl:36][C:37]1[N:55]=[C:40]2[C:41]([NH:45][CH2:46][C:47]3[CH:52]=[CH:51][C:50]([O:53][CH3:54])=[CH:49][CH:48]=3)=[CH:42][CH:43]=[CH:44][N:39]2[N:38]=1.[CH3:54][O:53][C:50]1[CH:49]=[CH:48][C:47]([CH2:46][NH:45][C:41]2[C:40]3[N:39]([N:38]=[C:37]([NH:35][C:32]4[CH:33]=[CH:34][C:29]([N:26]5[CH2:25][CH2:24][N:23]([CH3:22])[CH2:28][CH2:27]5)=[CH:30][CH:31]=4)[N:55]=3)[CH:44]=[CH:43][CH:42]=2)=[CH:52][CH:51]=1
Reactant: CN1CCN(c2ccc(N)cc2)CC1
Agent: COc1ccc(CN)cc1
Agent: COc1ccc(CNc2cccn3nc(Cl)nc23)cc1
Agent: Clc1nc2c(Br)cccn2n1
Product: COc1ccc(CNc2cccn3nc(Nc4ccc(N5CCN(C)CC5)cc4)nc23)cc1

Procedure:
(2-Chloro-[1,2,4]triazolo[1,5-a]pyridin-8-yl)-(4-methoxy-benzyl)-amine was prepared from 8-bromo-2-chloro-[1,2,4]triazolo[1,5-a]pyridine (2.00 g, 8.60 mmol), and 4-methoxy-benzenemethanamine, (1.26 mL, 9.72 mmol) in a manner analogous to Example 2d. Product isolated as an off-white solid, (1.51 g. 61%). 1H NMR (400 MHz, (D3C)2SO, δ, ppm): 8.06 (d, J=6.90 Hz, 1H), 7.31 (d, J=8.2 Hz, 2H), 7.19 (m, 1H), 6.94 (t, J=14.4, 7.6 Hz, 1H), 6.87 (d, J=7.4 Hz, 2H), 6.42 (d, J=8.0 Hz, 1H), 4.40 (d, J=6.1 Hz, 2H), 3.71 (s, 3H). MS=289 (MH)+. 391b) N(8)-(4-Methoxy-benzyl)-N(2)-[4-(4-methyl-piperazin-1-yl)-phenyl]-[1,2,4]triazolo[1,5-a]pyridine-2,8-diamine was prepared from 4-(4-methyl-piperazin-1-yl)-phenylamine (74.2 mg, 0.388 mmol) and (2-chloro-[1,2,4]triazolo[1,5-a]pyridin-8-yl)-(4-methoxy-benzyl)-amine (99.9 mg, 0.346 mmol) in a manner analogous to Example 2d. Product was isolated as a red foam (10.64 mg, 7%). 1H NMR (400 MHz, (D3C)2SO, δ, ppm): 9.03 (s, 1H), 7.92 (d, J=6.2 Hz, 1H), 7.56 (d, J=8.3 Hz, 2H), 7.32 (d, J=7.8 Hz, 2H), 6.88 (d, J=8.3 Hz, 4H), 6.68 (t, J=13.9, 7.0 Hz, 1H), 6.29 (m, 2H), 4.42 (m, 2H), 3.72 (s, 3H), 3.03 (s, 4H), 2.47 (s, 4H), 2.22 (s, 3H). MS=444 (MH)+.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9](=[O:24])[N:10]([CH2:22][OH:23])[CH:11]=[C:12]3[C:17]=2[NH:16][C:15]2[CH:18]=[CH:19][CH:20]=[CH:21][C:14]=2[S:13]3)=[CH:4][CH:3]=1.[C:25](Cl)(=[O:41])[CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH3:40]>N1C=CC=CC=1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9](=[O:24])[N:10]([CH2:22][O:23][C:25](=[O:41])[CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH3:40])[CH:11]=[C:12]3[C:17]=2[NH:16][C:15]2[CH:18]=[CH:19][CH:20]=[CH:21][C:14]=2[S:13]3)=[CH:4][CH:3]=1
Reactant: O=c1c(-c2ccc(Cl)cc2)c2c(cn1CO)Sc1ccccc1N2
Reactant: CCCCCCCCCCCCCCCC(=O)Cl
Solvent: c1ccncc1
Product: CCCCCCCCCCCCCCCC(=O)OCn1cc2c(c(-c3ccc(Cl)cc3)c1=O)Nc1ccccc1S2
Reaction time: 0.75 h
Yield: 34 %

Procedure:
To 3.0 g. of 4-(4-chlorophenyl)-2-(hydroxymethyl)-5H-pyrido[3,4-b][1,4]benzothiazin-3(2H)-one (8.4 mmol.) suspended in 30 ml. of pyridine at 0° C. was added dropwise 2.5 ml. of hexadecanoyl chloride (10.9 mmol.). After stirring for 45 minutes, the mixture was poured onto ice-water and allowed to stand for 16 hours at room temperature, resulting in the formation of a yellow precipitate. The precipitate was collected, washed with water and air-dried, then purified using flash chromatography on silica gel, using a mixture of 5% ethyl acetate: 95% methylene chloride as the eluent. Fractions containing the product were combined, and the solvent was removed in vacuo. The residue was triturated with diethyl ether to yield 4-(4-chlorophenyl)-2-[(1-oxohexadecyloxy)methyl]-5H-pyrido[3,4-b][1,4]benzothiazin-3(2H)-one as a light yellow solid (1.69 g; 34% yield) having the structural formula, ##STR18## a melting point in the range of 89°-92° C. and the following elemental analysis: