Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[CH:3]=[N:4][N:5]([CH:16]2[CH2:21][CH2:20][CH2:19][CH2:18][O:17]2)[C:6]=1[C:7]1[CH:14]=[CH:13][C:10]([C:11]#[N:12])=[C:9]([Cl:15])[CH:8]=1.[Cu][C:23]#[N:24]>CN(C)C=O>[Cl:15][C:9]1[CH:8]=[C:7]([C:6]2[N:5]([CH:16]3[CH2:21][CH2:20][CH2:19][CH2:18][O:17]3)[N:4]=[CH:3][C:2]=2[C:23]#[N:24])[CH:14]=[CH:13][C:10]=1[C:11]#[N:12]
Reactant: N#C[Cu]
Reactant: N#Cc1ccc(-c2c(Br)cnn2C2CCCCO2)cc1Cl
Solvent: CN(C)C=O
Product: N#Cc1ccc(-c2c(C#N)cnn2C2CCCCO2)cc1Cl
Temperature: 190 °C
Reaction time: 0.5 h

Procedure:
4-(4-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl)-2-chlorobenzonitrile (3 g, 8.18 mmol), copper(I) cyanide (0.733 g, 8.18 mmol) and N,N-dimethyl formamide (15 ml) were loaded in a microwave reactor tube. The mixture was heated 190° C. for 5 h. The reaction was quenched by pouring the mixture into 200 ml of 12% ammonia solution and stirred for 30 min. The precipitate was filtered, washed with water and dried in vacuum at 40° C. The product was used in the next step without further purification. LC-MS: [M+1]=313.75.
Reaction SMILES: [O:1]1[CH:3]([CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][O:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH2:2]1.[C:21]([CH2:24][N:25]1[CH2:36][CH2:35][NH:34][CH2:33][CH2:32][N:31]([CH2:37][C:38]([OH:40])=[O:39])[CH2:30][CH2:29][N:28]([CH2:41][C:42]([OH:44])=[O:43])[CH2:27][CH2:26]1)([OH:23])=[O:22].[OH-].[K+]>O1CCOCC1.O>[OH:1][CH:3]([CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][O:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[CH2:2][N:34]1[CH2:35][CH2:36][N:25]([CH2:24][C:21]([OH:23])=[O:22])[CH2:26][CH2:27][N:28]([CH2:41][C:42]([OH:44])=[O:43])[CH2:29][CH2:30][N:31]([CH2:37][C:38]([OH:40])=[O:39])[CH2:32][CH2:33]1
Reactant: c1ccc(COCCCCCCCCCC2CO2)cc1
Reactant: O=C(O)CN1CCNCCN(CC(=O)O)CCN(CC(=O)O)CC1
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: C1COCCO1
Product: O=C(O)CN1CCN(CC(=O)O)CCN(CC(O)CCCCCCCCCOCc2ccccc2)CCN(CC(=O)O)CC1
Temperature: 70 °C
Reaction time: 24 h

Procedure:
28.73 g (103.92 mmol) of 1,2-epoxy-11-benzyloxyundecane and 10 g (28.86 mmol) of 1,4,7-triscarboxymethyl-1,4,7,10-tetraazacyclododecane (=D03A) are dissolved in a mixture of 50 ml of dioxane/80 ml of water and the pH is brought to pH 10 with 6N potassium hydroxide solution. It is stirred for 24 hours at 70° C. It is evaporated to dryness, the residue is taken up with 200 ml of water/50 ml of methanol and extracted twice with 100 ml of tert-butyl methyl ether. The aqueous solution is adjusted to pH 3 with 5N hydrochloric acid and evaporated to dryness. The residue is boiled out (extracted) with 200 ml of methanol/80 ml of methylene chloride. It is cooled in an ice bath and filtered off from precipitated potassium chloride. The filtrate is concentrated by evaporation in a vacuum, the residue is dissolved in 45 ml of water/20 ml of ethanol and then added to a column of poly-(4-vinylpyridine). The product is eluted with a solution of ethanol/water 1:3. After concentration by evaporation in a vacuum, the residue is chromatographed on a reversed-phase column (RP 18/mobile solvent=gradient of water/tetrahydrofuran). After concentration by evaporation of the main fraction, 12.22 g (68% of theory) of a strongly hygroscopic, vitreous solid is obtained.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([Cl:9])=[CH:5][C:4]=1B(O)O.C(C1C=CC(B(O)O)=CC=1)(O)=O.Br[C:26]1[CH:27]=[C:28]([C:32]2[NH:36][N:35]=[N:34][N:33]=2)[CH:29]=[CH:30][CH:31]=1>>[Cl:9][C:6]1[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[C:4]([C:30]2[CH:31]=[CH:26][CH:27]=[C:28]([C:32]3[NH:36][N:35]=[N:34][N:33]=3)[CH:29]=2)[CH:5]=1
Reactant: COc1ccc(Cl)cc1B(O)O
Reactant: Brc1cccc(-c2nnn[nH]2)c1
Agent: O=C(O)c1ccc(B(O)O)cc1
Product: COc1ccc(Cl)cc1-c1cccc(-c2nnn[nH]2)c1

Procedure:
Following the procedure of Example 1b), except substituting 2-methoxy-5-chlorophenylboronic acid; for 4-carboxyphenylboronic acid; and substituting 5-(3-bromophenyl)-1H-tetrazole for the compound of 1a), the title compound was prepared (1.36 g; 100%) as a white solid. 1H NMR (300 MHz, d6-DMSO) δ 8.16 (s, 1H), 8.05 (d, J=7.6 Hz, 1H), 7.7 (d, J=6.6 Hz, 1H), 7.67 (t, J=7.7 Hz, 1H), 7.48 (m, 2H), 7.2 (d, J=9.1 Hz, 1H), 3.8 (s, 3H), MS (ES) m/z 287 [M+H].
Reaction SMILES: C(N(CC)CC)C.Cl[C:9]1[C:14]([N+:15]([O-:17])=[O:16])=[CH:13][CH:12]=[C:11]([Cl:18])[N:10]=1.[Cl:19][C:20]1[CH:21]=[C:22]([NH2:28])[C:23]([O:26][CH3:27])=[N:24][CH:25]=1>C(#N)C>[Cl:18][C:11]1[N:10]=[C:9]([NH:28][C:22]2[C:23]([O:26][CH3:27])=[N:24][CH:25]=[C:20]([Cl:19])[CH:21]=2)[C:14]([N+:15]([O-:17])=[O:16])=[CH:13][CH:12]=1
Reactant: O=[N+]([O-])c1ccc(Cl)nc1Cl
Reactant: COc1ncc(Cl)cc1N
Solvent: CCN(CC)CC
Solvent: CC#N
Product: COc1ncc(Cl)cc1Nc1nc(Cl)ccc1[N+](=O)[O-]
Temperature: 90 °C
Reaction time: 8 h
Yield: 39.2 %

Procedure:
Triethylamine (2.7 mL) and a catalytic amount of 4-diaminopyrimidine were added to a solution of 2,6-dichloro-3-nitropyridine (639 mg, 3.31 mmol) and 5-chloro-2-methoxy pyridin-3-amine (Preparation 23, 501 mg, 3.16 mmol) in acetonitrile (20 mL) and the resulting mixture was stirred overnight at 90° C. Solvent was then removed under reduced pressure until a solid precipitated. The solid was filtered, washed with acetonitrile and dried. The solid was then treated with dichloromethane, filtered, washed with more dichloromethane and the combined filtrate and washings were concentrated to dryness under reduced pressure to yield the title compound (390 mg 30%) as an orange solid.
Reaction SMILES: Br[CH2:2][N:3]1[C:7](=[O:8])[C:6]2=[CH:9][C:10]([NH:13][S:14]([C:17]3[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][CH:18]=3)(=[O:16])=[O:15])=[CH:11][CH:12]=[C:5]2[C:4]1=[O:24].[Na].[SH:26][C:27]1[N:31](C2C=CC=CC=2)[N:30]=[N:29][N:28]=1>O1CCCC1>[C:5]1([CH:2]([S:26][C:27]2[NH:31][N:30]=[N:29][N:28]=2)[N:3]2[C:7](=[O:8])[C:6]3=[CH:9][C:10]([NH:13][S:14]([C:17]4[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][CH:18]=4)(=[O:16])=[O:15])=[CH:11][CH:12]=[C:5]3[C:4]2=[O:24])[CH:6]=[CH:9][CH:10]=[CH:11][CH:12]=1
Reactant: Cc1ccc(S(=O)(=O)Nc2ccc3c(c2)C(=O)N(CBr)C3=O)cc1
Reactant: Sc1nnnn1-c1ccccc1
Agent: [Na]
Solvent: C1CCOC1
Product: Cc1ccc(S(=O)(=O)Nc2ccc3c(c2)C(=O)N(C(Sc2nnn[nH]2)c2ccccc2)C3=O)cc1
Reaction time: 2 h
Yield: 191.4 %

Procedure:
N-Bromomethyl-4-(p-toluenesulfonamido)phthalimide (13 g) was dissolved in tetrahydrofuran (200 ml) and thereto a tetrahydrofuran solution (100 ml) of the sodium salt of 5-mercapto-1-phenyltetrazole (6 g) was slowly added at room temperature. The reaction mixture was allowed to stand at room temperature for 2 hours. Thereafter, the reaction mixture was poured into ice-cold water, and the crystals precipitated were recovered by filtration to obtain a crude product. The thus obtained crude product was recrystallized from an ethyl acetate/methanol mixed solvent to yield 15.4 g of N-(1-phenyl-5-tetrazolylthiomethyl)-4-(p-toluenesulfonamido)phthalimide. Melting Point: 202°-204° C.
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([NH2:8])[CH:5]=[CH:4][C:3]=1[NH:9][CH2:10][CH2:11][N:12]1[CH2:17][CH2:16][O:15][CH2:14][CH2:13]1.C[Al](C)C.C[O:23][C:24](=O)/[CH:25]=[C:26](\[NH:28][C:29](=O)[CH2:30][O:31][C:32]1[CH:37]=[CH:36][CH:35]=[C:34]([F:38])[CH:33]=1)/[CH3:27].O>C(Cl)Cl>[F:1][C:2]1[CH:7]=[C:6]([N:8]2[C:24](=[O:23])[CH:25]=[C:26]([CH3:27])[N:28]=[C:29]2[CH2:30][O:31][C:32]2[CH:37]=[CH:36][CH:35]=[C:34]([F:38])[CH:33]=2)[CH:5]=[CH:4][C:3]=1[NH:9][CH2:10][CH2:11][N:12]1[CH2:17][CH2:16][O:15][CH2:14][CH2:13]1
Reactant: Nc1ccc(NCCN2CCOCC2)c(F)c1
Reactant: COC(=O)/C=C(/C)NC(=O)COc1cccc(F)c1
Agent: C[Al](C)C
Solvent: ClCCl
Solvent: O
Product: Cc1cc(=O)n(-c2ccc(NCCN3CCOCC3)c(F)c2)c(COc2cccc(F)c2)n1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 79.4 %

Procedure:
To a solution of 2-fluoro-N1-(2-morpholinoethyl)benzene-1,4-diamine (0.33 g, 1.38 mmol) in DCM (20 mL) was added trimethylaluminium (2.1 mL, 4.2 mmol, 2 M in toluene) slowly and the mixture was stirred at rt for 0.5 h. A solution of (Z)-methyl-3-(2-(3-fluorophenoxy)acetamido)but-2-enoate (0.37 g, 1.38 mmol) in DCM (5 mL) was added slowly and the resulting mixture was stirred at rt for 24 h. 50 mL of water was then added to the mixture slowly and the mixture was extracted with CH2Cl2 (50 mL×2). The combined organic phases were washed with brine (100 mL×3), dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was purified by a silica gel column chromatography (EtOAc) to give the title compound as a pale yellow solid (0.5 g, 79%). The compound was characterized by the following spectroscopic data:
Reaction SMILES: [CH3:1][C:2](O)([CH2:5][CH2:6][CH:7]=[C:8]([CH3:13])[CH2:9][CH:10]([CH3:12])[CH3:11])[CH:3]=[CH2:4].P(Br)(Br)[Br:16]>>[Br:16][CH2:4][CH:3]=[C:2]([CH3:1])[CH2:5][CH2:6][CH:7]=[C:8]([CH3:13])[CH2:9][CH:10]([CH3:12])[CH3:11]
Reactant: C=CC(C)(O)CCC=C(C)CC(C)C
Reactant: BrP(Br)Br
Product: CC(=CCBr)CCC=C(C)CC(C)C

Procedure:
Following the procedure of Example 9, 3,7,9-trimethyl-1,6-decadien-3-ol and phosphorus tribromide are reacted to form 1-bromo-3,7,9-trimethyl-2,6-decadiene.
Reaction SMILES: [CH2:1]([S:3]([C:6]1[CH:11]=[CH:10][C:9](F)=[CH:8][CH:7]=1)(=[O:5])=[O:4])[CH3:2].C1C(S(Cl)(=O)=O)=CC=C([I:23])C=1>>[CH2:1]([S:3]([C:6]1[CH:11]=[CH:10][C:9]([I:23])=[CH:8][CH:7]=1)(=[O:5])=[O:4])[CH3:2]
Reactant: CCS(=O)(=O)c1ccc(F)cc1
Reactant: O=S(=O)(Cl)c1ccc(I)cc1
Product: CCS(=O)(=O)c1ccc(I)cc1
Yield: 20 %

Procedure:
Compound 5e was prepared in analogy to Compound 5a, starting from pipsyl chloride (10 mmol, 3.02 g). A white solid was crystallized from ethyl acetate and hexane. HPLC indicated 100% purity, mp 78-79° C., (0.60 g, 20% yield). 1H NMR (CDCl3): 1.28 (t, 3H, CH3), 3.12 (q, 2H, CH2), 7.63 (d, 2H, Ar—H), 7.96 (d, 2H, Ar—H); MS: 296 M+. Elemental Analysis (C, H, I, S) for C8H9IO2S.0.2C6H14-0.1H2O; calculated C, 35.06; H, 3.83; I, 40.26; S, 10.17. found C, 35.04; H, 3.41; I, 40.32; S, 9.74.
Reaction SMILES: [NH2:1][C:2]1([C:8]([O:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[O:9])[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]1.CC1C=CC(S(O)(=O)=O)=CC=1.C(N(CC)CC)C.[N:36]1([C:42](Cl)=[O:43])[CH2:41][CH2:40][O:39][CH2:38][CH2:37]1>C(=O)([O-])[O-].[Na+].[Na+].C(Cl)(Cl)Cl>[N:36]1([C:42]([NH:1][C:2]2([C:8]([O:10][CH2:11][C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=3)=[O:9])[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]2)=[O:43])[CH2:41][CH2:40][O:39][CH2:38][CH2:37]1
Reactant: O=C(Cl)N1CCOCC1
Reactant: NC1(C(=O)OCc2ccccc2)CCCCC1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: ClC(Cl)Cl
Solvent: CCN(CC)CC
Product: O=C(NC1(C(=O)OCc2ccccc2)CCCCC1)N1CCOCC1
Temperature: 60 °C
Yield: 87.2 %

Procedure:
After neutralizing 203 g (500 mmol) of phenylmethyl 1-aminocyclohexanecarboxylate•p-toluenesulfonate with a 10% sodium carbonate solution, the mixture was extracted with chloroform and dried over anhydrous magnesium sulfate. The solid material was filtered off, and after adding 56 g (550 mmol) of triethylamine to the chloroform layer, 75 g (500 mmol) of 4-morpholinecarbonyl chloride was added dropwise, and the mixture was heated in an oil bath (60° C.) for 3 days. After completion of the reaction, the reaction mixture was washed successively in the order of water, a 10% aqueous potassium hydrogen sulfate solution, a saturated aqueous sodium hydrogen carbonate solution and a saturated NaCl solution, and dried over anhydrous sodium sulfate. After removing the solvent under reduced pressure, the resulting crystals were washed with ether to obtain 151 g (Yield: 87%) of the title compound.
Reaction SMILES: [C:1]([C:5]1[CH:10]=[CH:9][C:8]([OH:11])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[CH3:12][C:13](=C)[CH3:14].OC1C=CC(C(C2C=CC(O)=CC=2)(C)C)=CC=1>>[OH:11][C:8]1[CH:7]=[C:6]2[C:5](=[CH:10][CH:9]=1)[C:1]([CH3:4])([CH3:2])[CH2:3][C:13]2([CH3:14])[CH3:12]
Reactant: CC(C)(C)c1ccc(O)cc1
Reactant: C=C(C)C
Agent: CC(C)(c1ccc(O)cc1)c1ccc(O)cc1
Product: CC1(C)CC(C)(C)c2cc(O)ccc21
Temperature: 180 °C
Reaction time: 4 h
Yield: 234 %

Procedure:
750 g (5 mol) of 4-tert.-butylphenol and 320 g of an acid-activated fuller's earth are introduced into a 10 liter autoclave and heated to 180° C. 1960 g (35 mol) of isobutylene and 3420 g (15 mol) of molten 2,2-bis-(4-hydroxyphenyl)-propane are simultaneously pumped in over a period of 4 to 5 hours at the aforementioned temperature. The mixture is then left to react with stirring for another 4 hours at 180° C. The hot reaction mixture is then filtered off from the catalyst, giving 6100 g of a crude mixture from which 2230 g (11.7 mol) of 5-hydroxy-1,1,3,3-tetramethyl indane are obtained by fractional distillation.
Reaction SMILES: C(N(CC)CC)C.Cl.[CH3:9][C@@:10]12[C:17]([CH3:19])([CH3:18])[CH:14]([CH2:15][CH2:16]1)[CH2:13][NH:12][CH2:11]2.[OH:20][CH:21]1[CH:28]2[CH2:29][CH:24]3[CH2:25][CH:26]([CH2:30][CH:22]1[CH:23]3[CH2:31][C:32](O)=[O:33])[CH2:27]2.CCN=C=NCCCN(C)C>C(Cl)Cl>[OH:20][CH:21]1[CH:28]2[CH2:29][CH:24]3[CH2:25][CH:26]([CH2:30][CH:22]1[CH:23]3[CH2:31][C:32]([N:12]1[CH2:13][CH:14]3[C:17]([CH3:19])([CH3:18])[C@:10]([CH3:9])([CH2:16][CH2:15]3)[CH2:11]1)=[O:33])[CH2:27]2
Reactant: O=C(O)CC1C2CC3CC(C2)C(O)C1C3
Reactant: CC1(C)C2CC[C@]1(C)CNC2
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC1(C)C2CC[C@]1(C)CN(C(=O)CC1C3CC4CC(C3)C(O)C1C4)C2
Reaction time: 0.5 h

Procedure:
Triethylamine 0.23 ml was added to a methylene chloride 5 ml solution of (IS)-1,8,8-trimethyl-3-azabicyclo[3.2.1]octane hydrochloride 0.26 g and stirred at O@C for 30 min. 4-hydroxy-2-adamantyl acetic acid 0.26 g and WSC 0.31 g were added therein, then temperature of the reaction mixture was gradually changed to room temperature and stirred for 25 hours. The reaction mixture was washed with saturated aqueous sodium chloride solution and dried by anhydrous sodium sulfate. After filtering the drying agent, the filtrate was concentrated in vacuo to obtain crude (IS)-3-(4-hydroxy-2-adamantylacetyl)1,8,8-trimethyl-3-azabicyclo[3.2.1]octane. The concentrate was added to THF 25 ml solution of lithium aluminum hydride 70.5 mg and refluxed under heating for 1.5 hours. The reaction mixture was cooled, then water was added thereto and the insoluble material was removed by filtration. The filtrate was concentrated in vacuo. The thus obtained residue was purified by means of silica gel column chromatography (Wako gel, C200, chloroform methanol=150:1) to obtain the product.
Reaction SMILES: C(NC1C=CC(C2C=C3C(CN([C@@H](C(C)C)C(O)=O)C3=O)=CC=2)=CC=1)(=O)C1C=CC=CC=1.[C:33]([C:37]1[CH:69]=[CH:68][C:40]([C:41]([NH:43][C:44]2[CH:49]=[CH:48][C:47]([C:50]3[CH:58]=[C:57]4[C:53]([CH2:54][N:55]([C@@H:60]([CH:65]([CH3:67])[CH3:66])[C:61]([O:63]C)=[O:62])[C:56]4=[O:59])=[CH:52][CH:51]=3)=[CH:46][CH:45]=2)=[O:42])=[CH:39][CH:38]=1)([CH3:36])([CH3:35])[CH3:34]>>[C:33]([C:37]1[CH:69]=[CH:68][C:40]([C:41]([NH:43][C:44]2[CH:45]=[CH:46][C:47]([C:50]3[CH:58]=[C:57]4[C:53]([CH2:54][N:55]([C@@H:60]([CH:65]([CH3:66])[CH3:67])[C:61]([OH:63])=[O:62])[C:56]4=[O:59])=[CH:52][CH:51]=3)=[CH:48][CH:49]=2)=[O:42])=[CH:39][CH:38]=1)([CH3:35])([CH3:34])[CH3:36]
Reactant: COC(=O)[C@H](C(C)C)N1Cc2ccc(-c3ccc(NC(=O)c4ccc(C(C)(C)C)cc4)cc3)cc2C1=O
Agent: CC(C)[C@@H](C(=O)O)N1Cc2ccc(-c3ccc(NC(=O)c4ccccc4)cc3)cc2C1=O
Product: CC(C)[C@@H](C(=O)O)N1Cc2ccc(-c3ccc(NC(=O)c4ccc(C(C)(C)C)cc4)cc3)cc2C1=O
Yield: 87 %

Procedure:
The compound of example 116 was prepared analogous to compound of example 98 by hydrolysis of compound of example 115.
Reaction SMILES: [C:1]1([CH:7]([S:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][N+:11]=2[O-:16])[CH3:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(O)(=[O:19])C.OO>[O-][W]([O-])(=O)=O.[Na+].[Na+].O>[C:1]1([CH:7]([S:9]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][N+:11]=2[O-:16])=[O:19])[CH3:8])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: CC(Sc1cccc[n+]1[O-])c1ccccc1
Reactant: CC(=O)O
Agent: O=[W](=O)([O-])[O-]
Agent: OO
Agent: [Na+]
Solvent: O
Product: CC(c1ccccc1)S(=O)c1cccc[n+]1[O-]

Procedure:
To a mixture of 23.2 g (0.1 mole) of 2-(1-phenylethylthio)pyridine N-oxide, 0.2 g of sodium tungstate, and 60 ml of glacial acetic acid were added 10 ml (0.1 mole) of 30% hydrogen peroxide over approximately 0.5 hours. The mixture exothermed somewhat to about 65° C. After completion of the reaction, the reaction mixture was poured slowly into 800 ml of vigorously stirred cold water. A solid separated out and was filtered off and washed with 15 ml of cold ethanol. The solid was air dried, melting point 130–130.5° C. Yield 14.5 g or 59%. An infrared spectrum confirmed the structure.
Reaction SMILES: [Cl:1][C:2]1[CH:8]=[CH:7][CH:6]=[C:5]([Cl:9])[C:3]=1[NH2:4].[C:10]([NH:18][C:19]1[NH:23][N:22]=[C:21]([S:24](Cl)(=[O:26])=[O:25])[N:20]=1)(=[O:17])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1>N1C=CC=CC=1>[C:10]([NH:18][C:19]1[NH:23][N:22]=[C:21]([S:24]([NH:4][C:3]2[C:2]([Cl:1])=[CH:8][CH:7]=[CH:6][C:5]=2[Cl:9])(=[O:26])=[O:25])[N:20]=1)(=[O:17])[C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1
Reactant: Nc1c(Cl)cccc1Cl
Reactant: O=C(Nc1nc(S(=O)(=O)Cl)n[nH]1)c1ccccc1
Solvent: c1ccncc1
Product: O=C(Nc1nc(S(=O)(=O)Nc2c(Cl)cccc2Cl)n[nH]1)c1ccccc1
Yield: 49.5 %

Procedure:
A small flask equipped with a magnetic stirrer and protected from the atmosphere by a drying tube was charged with 8.1 g (0.05 mole) of 2,6-dichloroaniline, 20 ml of dry pyridine and then 14.4 g (0.05 mole) of dry 5-benzoylamino-3-chlorosulfonyl-1,2,4-triazole was added over about 1 minute with vigorous stirring. After the exotherm had subsided somewhat, the mixture was heated with an oil bath maintained at 100°-106° C. for 3 hours with stirring. The mixture was next concentrated under reduced pressure on a rotary evaporator to remove the bulk of the pyridine (80° C./1 mm) and then taken up in a mixture of 25 ml of concentrated aqueous ammonia, 125 ml of water and 100 ml of methylene chloride. After cooling and filtration to remove the insoluble material, the methylene chloride phase was removed and the pH of the aqueous phase was adjusted to 2.5 with hydrochloric acid. The precipitate that formed was collected by filtration, washed with water, and dried to obtain 10.2 g (50 percent of theory) of the title sulfonamide. A sample purified by recrystallization from acetonitrile melted at 321°-322° (dec.). The carbon nmr spectrum was consistent with the assigned structure, having absorptions at 159.2, 149.7, 165.6, 135.9, 130.8, 128.9, 130.0, 132.8, 128.0, 128.1, and 131.7 ppm.
Reaction SMILES: [NH2:1][C:2]1[S:3][C:4]2[CH2:5][CH2:6][N:7]([CH2:12][CH:13]=[CH:14][C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([O:21]CC4C=CC=CC=4)[CH:16]=3)[CH2:8][CH2:9][C:10]=2[N:11]=1.B(Br)(Br)Br.CCOCC>C(Cl)Cl>[NH2:1][C:2]1[S:3][C:4]2[CH2:5][CH2:6][N:7]([CH2:12][CH:13]=[CH:14][C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([OH:21])[CH:16]=3)[CH2:8][CH2:9][C:10]=2[N:11]=1
Reactant: Nc1nc2c(s1)CCN(CC=Cc1cccc(OCc3ccccc3)c1)CC2
Agent: BrB(Br)Br
Solvent: ClCCl
Solvent: CCOCC
Product: Nc1nc2c(s1)CCN(CC=Cc1cccc(O)c1)CC2
Yield: 71 %

Procedure:
Prepared from 2-amino-6-(3-(3-benzyloxy-phenyl)allyl)-4,5,7,8-tetrahydro-6H- thiazolo[5,4-d]azepine with 2 equivalents of boron tribromide in methylene chloride. Yield: 71% of theory, Melting point: 85°-95° C. (ether); foamy.
Reaction SMILES: [CH:1]1[N:6]=[C:5]2[N:7]([C@@H:10]3[O:14][C@H:13]([CH2:15][O:16][P:17]([O:20][P:21]([O:24][P:25]([OH:28])([OH:27])=[O:26])([OH:23])=[O:22])([OH:19])=[O:18])[C@@H:12]([OH:29])[CH2:11]3)[CH:8]=[N:9][C:4]2=[C:3]([NH2:30])[N:2]=1.[OH:31]P(=O)(OC[C@H]1O[C@@H](N2C=C(C)C(=O)NC2=O)C[C@@H]1O)OP(=O)(OP(=O)(O)O)O.P(OC[C@H]1O[C@@H](N2C3N=C(N)NC(=O)C=3N=C2)C[C@@H]1O)(OP(OP(O)(O)=O)(O)=O)(=O)O.P(OC[C@H]1O[C@@H](N2C=CC(N)=NC2=O)C[C@@H]1O)(OP(OP(O)(O)=O)(O)=O)(=O)O>>[P:17]([O:16][CH2:15][C@H:13]1[O:14][C@@H:10]([N:7]2[C:5]3[N:6]=[CH:1][N:2]=[C:3]([NH2:30])[C:4]=3[N:9]=[CH:8]2)[C@H:11]([OH:31])[C@@H:12]1[OH:29])([O:20][P:21]([O:24][P:25]([OH:28])([OH:27])=[O:26])([OH:23])=[O:22])(=[O:19])[OH:18]
Reactant: Nc1ncnc2c1ncn2[C@H]1C[C@H](O)[C@@H](COP(=O)(O)OP(=O)(O)OP(=O)(O)O)O1
Reactant: Cc1cn([C@H]2C[C@H](O)[C@@H](COP(=O)(O)OP(=O)(O)OP(=O)(O)O)O2)c(=O)[nH]c1=O
Agent: Nc1ccn([C@H]2C[C@H](O)[C@@H](COP(=O)(O)OP(=O)(O)OP(=O)(O)O)O2)c(=O)n1
Agent: Nc1nc2c(ncn2[C@H]2C[C@H](O)[C@@H](COP(=O)(O)OP(=O)(O)OP(=O)(O)O)O2)c(=O)[nH]1
Product: Nc1ncnc2c1ncn2[C@@H]1O[C@H](COP(=O)(O)OP(=O)(O)OP(=O)(O)O)[C@@H](O)[C@H]1O

Procedure:
1 μL 6.25 mM dNTP mixture of equimolar amounts of dATP, dTTP, dGTP, dCTP
Reaction SMILES: [CH2:1]([C@@H:8]1[O:10][C@@H:9]1[CH2:11][OH:12])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH3:7].[Cr](O[Cr]([O-])(=O)=O)([O-])(=O)=[O:14].[NH+]1C=CC=CC=1.[NH+]1C=CC=CC=1>CN(C=O)C.O.Cl>[CH2:1]([C@H:8]1[O:10][C@H:9]1[C:11]([OH:14])=[O:12])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH3:7]
Reactant: CCCCCCC[C@@H]1O[C@@H]1CO
Reactant: O=[Cr](=O)([O-])O[Cr](=O)(=O)[O-]
Agent: Cl
Agent: c1cc[nH+]cc1
Solvent: O
Solvent: CN(C)C=O
Product: CCCCCCC[C@H]1O[C@H]1C(=O)O
Reaction time: 8 h

Procedure:
To a solution of 300 mg (1.16 mmole) (2R-cis)-3-heptyloxiranemethanol in 50 ml of DMF was added 2.62 g (6.97 mmole) of pyridinium dichromate. The reaction was allowed to stir overnight under argon. The mixture was then diluted with 150 ml H2O and 20 ml 0.1M HCl and washed three times with 50 ml of Et2O. The combined Et2O layers are dried over MgSO4, filtered and evaporated to afford a white powder. This residue was crystallized from petroleum ether to afford 155 mg of white power, mp 53°-5° C. 1H NMR (CDCl3) δ3.60 (d, 1, J=5 Hz), 3.24 (dd, 1, J=5 12 Hz), 1.6-1.2 (m, 12), 0.88 (t, 3, J=7 Hz). Mass Spectra: M-45(--CO2H)(3.7)141.1, M(100)41.0.
Reaction SMILES: FC(F)(F)S([O:6][S:7]([C:10]([F:13])([F:12])[F:11])(=[O:9])=[O:8])(=O)=O.[Cl:16][C:17]1[CH:36]=[CH:35][C:20]([O:21][C:22]2[C:31]3[C:26](=[CH:27][C:28](O)=[C:29]([O:32][CH3:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)=[C:19]([F:37])[CH:18]=1.N1C=CC=CC=1>C(Cl)Cl>[Cl:16][C:17]1[CH:36]=[CH:35][C:20]([O:21][C:22]2[C:31]3[C:26](=[CH:27][C:28]([O:6][S:7]([C:10]([F:11])([F:12])[F:13])(=[O:8])=[O:9])=[C:29]([O:32][CH3:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)=[C:19]([F:37])[CH:18]=1
Reactant: COc1cc2c(Oc3ccc(Cl)cc3F)ncnc2cc1O
Reactant: O=S(=O)(OS(=O)(=O)C(F)(F)F)C(F)(F)F
Solvent: ClCCl
Solvent: c1ccncc1
Product: COc1cc2c(Oc3ccc(Cl)cc3F)ncnc2cc1OS(=O)(=O)C(F)(F)F
Temperature: 5 °C
Reaction time: 1 h
Yield: 88.5 %

Procedure:
Trifluoromethanesulphonic anhydride (338 mg, 1.2 mmol) was added to a suspension of 4-(4-chloro-2-fluorophenoxy)-7-hydroxy-6-methoxyquinazoline (320 mg, I mmol), (prepared as described for the starting material in Example 5), in methylene chloride (2 ml) containing pyridine (2 ml) cooled at 5° C. When the addition was complete, the mixture was left to warm to ambient temperature and stirred for 1 hour. After removal of the volatiles by evaporation, the residue was partitioned between ethyl acetate/ether and water. The organic layer was separated, washed with 0.5M hydrochloric acid, followed by water, brine, dried (MgSO4) and evaporated to give 4-(4-chloro-2-fluorophenoxy)-6-methoxy-7-(trifluoromethylsulphonyloxy)quinazoline (400 mg, 88%).