Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][N:3]=[C:4]([C:10](=[O:13])[CH2:11][CH3:12])[C:5]([O:7][CH2:8][CH3:9])=[O:6].S(Cl)([Cl:17])(=O)=O>C(O)(=O)C>[CH3:1][O:2][N:3]=[C:4]([C:10](=[O:13])[CH:11]([Cl:17])[CH3:12])[C:5]([O:7][CH2:8][CH3:9])=[O:6]
Reactant: O=S(=O)(Cl)Cl
Reactant: CCOC(=O)C(=NOC)C(=O)CC
Solvent: CC(=O)O
Product: CCOC(=O)C(=NOC)C(=O)C(C)Cl
Temperature: 25 °C
Reaction time: 2.5 h
Yield: 91.9 %

Procedure:
A mixture of ethyl 2-methoxyimino-2-propionylacetate (14.7 g.), sulfuryl chloride (10.9 g.) and acetic acid (14.7 ml.) was stirred at room temperature for an hour and then at 40° C. for 2.5 hrs. Ice-water was added to the reaction mixture, adjusted to pH 6.5 and extracted with methylene chloride. The extract was washed with an aqueous solution of sodium chloride, dried over magnesium sulfate and then filtered. The filtrate was evaporated in vacuo to give ethyl 2-methoxyimino-2-(2-chloropropionyl)acetate (16.0 g.).
Reaction SMILES: [OH:1][CH:2]([CH3:7])[CH2:3][C:4]([OH:6])=[O:5].[CH3:8][C:9]([Si:12](Cl)([CH3:14])[CH3:13])([CH3:11])[CH3:10]>C(Cl)Cl>[C:9]([Si:12]([CH3:14])([CH3:13])[O:1][CH:2]([CH3:7])[CH2:3][C:4]([OH:6])=[O:5])([CH3:11])([CH3:10])[CH3:8]
Reactant: CC(C)(C)[Si](C)(C)Cl
Reactant: CC(O)CC(=O)O
Solvent: ClCCl
Product: CC(CC(=O)O)O[Si](C)(C)C(C)(C)C
Temperature: 25 °C
Reaction time: 8 h

Procedure:
3-Hydroxy-butyric acid (500 mg, 4.8 mmol) is dissolved in a mixture of TBSCl (1.5 g, 10.1 mmol) in dry DCM (48 mL). The resulting mixture is stirred overnight at room temperature. The resulting suspension is then filtered and the obtained residues are washed with DCM, then stirred in Et2O and filtered. The obtained filtrate is evaporated to give the desired product that is used as such.
Reaction SMILES: Cl[CH2:2][CH2:3][CH:4]([N:21]1[CH:25]=[CH:24][CH:23]=[N:22]1)[C:5]1[C:14]([Cl:15])=[C:13]([Cl:16])[CH:12]=[C:11]2[C:6]=1[N:7]=[C:8]([O:19][CH3:20])[C:9]([O:17][CH3:18])=[N:10]2.[CH3:26][C:27]([NH2:31])([CH3:30])[CH2:28][CH3:29]>C(O)C>[Cl:15][C:14]1[C:5]([CH:4]([CH2:3][CH2:2][NH:31][C:27]([CH3:30])([CH3:26])[CH2:28][CH3:29])[N:21]2[CH:25]=[CH:24][CH:23]=[N:22]2)=[C:6]2[C:11](=[CH:12][C:13]=1[Cl:16])[N:10]=[C:9]([O:17][CH3:18])[C:8]([O:19][CH3:20])=[N:7]2
Reactant: COc1nc2cc(Cl)c(Cl)c(C(CCCl)n3cccn3)c2nc1OC
Reactant: CCC(C)(C)N
Solvent: CCO
Product: CCC(C)(C)NCCC(c1c(Cl)c(Cl)cc2nc(OC)c(OC)nc12)n1cccn1
Temperature: 105 °C
Yield: 38 %

Procedure:
A mixture of 5-[(2-chloroethyl)pyrazol-1-ylmethyl]-6,7-dichloro-2,3-dimethoxyquinoxaline (150 mg, 0.37 mmol), 1,1-dimethyl-1-propylamine (3 mL) and ethanol (5 mL) were heated in a closed vessel at 105° C. for 7 hours. The mixture was cooled, the solvent was removed under reduced pressure, and the residue was dissolved in ethyl acetate (75 mL). The solution was washed with saturated aqueous sodium bicarbonate, dried (MgSO4) and concentrated under reduced pressure. Purification by flash chromatography (elution with dichloromethane, then an ethyl acetate/methanol/triethylamine gradient) gave 6,7-dichloro-2,3-dimethoxy-5-{[2-(N-(1,1-dimethylpropyl)amino)ethyl]pyrazol-1-ylmethyl}quinoxaline (65 mg, 38%), as a pale yellow solid.
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][Br:7].[CH2:8]([C:10]1[CH:15]=[CH:14][C:13]([CH2:16][CH2:17][OH:18])=[CH:12][CH:11]=1)[CH3:9]>>[Br:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][O:18][CH2:17][CH2:16][C:13]1[CH:14]=[CH:15][C:10]([CH2:8][CH3:9])=[CH:11][CH:12]=1
Reactant: CCc1ccc(CCO)cc1
Reactant: BrCCCCCBr
Product: CCc1ccc(CCOCCCCCBr)cc1

Procedure:
(2.19 g) T.l.c. [K] Rf 0.48, from 1,5-dibromopentane (7.8 g) and 4- ethylbenzeneethanol (1.7 g).
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[C:6]([C:8]#[C:9][C:10]2[N:11]=[C:12]([CH3:15])[NH:13][CH:14]=2)[CH:5]=[CH:4][N:3]=1.[F:16][C:17]1[CH:24]=[CH:23][C:20]([CH2:21]Br)=[CH:19][CH:18]=1>>[F:16][C:17]1[CH:24]=[CH:23][C:20]([CH2:21][N:13]2[CH:14]=[C:10]([C:9]#[C:8][C:6]3[CH:5]=[CH:4][N:3]=[C:2]([CH3:1])[CH:7]=3)[N:11]=[C:12]2[CH3:15])=[CH:19][CH:18]=1
Reactant: Fc1ccc(CBr)cc1
Reactant: Cc1cc(C#Cc2c[nH]c(C)n2)ccn1
Product: Cc1cc(C#Cc2cn(Cc3ccc(F)cc3)c(C)n2)ccn1

Procedure:
The title compound, MS: m/e=306.2 (M+H+), was prepared in accordance with the general method of example 1 from 2-methyl-4-(2-methyl-1H-imidazol-4-ylethynyl)-pyridine and 4-fluoro-benzylbromide.
Reaction SMILES: [Cl:1][C:2]1[CH:12]=[CH:11][C:5]([C:6]([N:8]=[C:9]=[S:10])=[O:7])=[CH:4][CH:3]=1.[NH2:13][C:14]1[CH:22]=[CH:21][CH:20]=[CH:19][C:15]=1[C:16]([NH2:18])=[O:17]>O1CCCC1>[NH2:18][C:16]([C:15]1[CH:19]=[CH:20][CH:21]=[CH:22][C:14]=1[NH:13][C:9](=[S:10])[NH:8][C:6](=[O:7])[C:5]1[CH:11]=[CH:12][C:2]([Cl:1])=[CH:3][CH:4]=1)=[O:17]
Reactant: O=C(N=C=S)c1ccc(Cl)cc1
Reactant: NC(=O)c1ccccc1N
Solvent: C1CCOC1
Product: NC(=O)c1ccccc1NC(=S)NC(=O)c1ccc(Cl)cc1
Reaction time: 3 h
Yield: 85.8 %

Procedure:
To a stirred mixture of 10.5 g of 4-chlorobenzoyl isothiocyanate in 100 ml of tetrahydrofuran was added a mixture of 6.8 g of 2-aminobenzamide in 200 ml of tetrahydrofuran. After stirring for 3 hours the solid was collected, giving 14.3 g of N-[[[2-(aminocarbonyl)phenyl]amino]thioxomethyl]-4-chlorobenzamide.
Reaction SMILES: [OH:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[O:5][C:4](=[O:12])[CH:3]=1.P(Cl)(Cl)(Cl)=O.[C:18](O)(=[O:20])[CH3:19]>>[C:18]([C:3]1[C:4](=[O:12])[O:5][C:6]2[C:11]([C:2]=1[OH:1])=[CH:10][CH:9]=[CH:8][CH:7]=2)(=[O:20])[CH3:19]
Reactant: CC(=O)O
Reactant: O=c1cc(O)c2ccccc2o1
Solvent: O=P(Cl)(Cl)Cl
Product: CC(=O)c1c(O)c2ccccc2oc1=O
Temperature: 0 °C

Procedure:
120 g of 4-hydroxycoumarin in 600 ml of glacial acetic acid are heated to the boil and 380 ml of phosphorus oxychloride are added dropwise in the course of 60 minutes at the boil. The reaction mixture is heated to the boil under reflux for a further 30 minutes and is cooled and discharged into 4 l of ice-water. The crystalline residue is filtered off, washed with water and dried in vacuo at 50° C. 127 g of 3-acetyl-4-hydroxycoumarin are obtained.
Reaction SMILES: [C:1]([C:4]1[C:5](Cl)=[C:6]2[CH:12]=[N:11][N:10]([CH2:13][CH3:14])[C:7]2=[N:8][CH:9]=1)(=[O:3])[CH3:2].Cl.[NH2:17]O.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.O>C(O)(=O)C>[CH2:13]([N:10]1[C:7]2[N:8]=[CH:9][C:4]3[C:5](=[N:17][O:3][C:1]=3[CH3:2])[C:6]=2[CH:12]=[N:11]1)[CH3:14]
Reactant: NO
Reactant: CCn1ncc2c(Cl)c(C(C)=O)cnc21
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: Cl
Solvent: O
Solvent: CC(=O)O
Product: CCn1ncc2c3noc(C)c3cnc21

Procedure:
5-Acetyl-4-chloro-1-ethyl-1H-pyrazolo[3,4-b]pyridine (4.60 g) was refluxed for 2 hours in 450 ml of glacial acetic acid containing 15 g of hydroxylamine hydrochloride and 1.0 g of p-toluenesulfonic acid monohydrate. At the end of this time the reaction volume was reduced to ca. 200 ml under reduced pressure and then it was poured into 800 ml of water. The amorphous precipitate was filtered off and purified over 230-400 mesh silica gel (5% ethyl acetate/dichloromethane). The appropriate fractions were combined and evaporated and the resultant crystalline product was washed with pentane to give 1.75 g, mp 181°-182° C.
Reaction SMILES: C[Si](I)(C)C.[OH:6][NH:7][C:8](=[O:42])[C@H:9]([NH:25][S:26]([N:29]1[CH2:34][CH2:33][N:32]([C:35]2[CH:40]=[CH:39][C:38]([Cl:41])=[CH:37][CH:36]=2)[CH2:31][CH2:30]1)(=[O:28])=[O:27])[CH2:10][CH2:11][CH2:12][CH2:13][NH:14]C(OCC1C=CC=CC=1)=O.CO>C(#N)C>[OH:6][NH:7][C:8](=[O:42])[C@H:9]([NH:25][S:26]([N:29]1[CH2:30][CH2:31][N:32]([C:35]2[CH:36]=[CH:37][C:38]([Cl:41])=[CH:39][CH:40]=2)[CH2:33][CH2:34]1)(=[O:28])=[O:27])[CH2:10][CH2:11][CH2:12][CH2:13][NH2:14]
Reactant: O=C(NCCCC[C@@H](NS(=O)(=O)N1CCN(c2ccc(Cl)cc2)CC1)C(=O)NO)OCc1ccccc1
Agent: C[Si](C)(C)I
Solvent: CO
Solvent: CC#N
Product: NCCCC[C@@H](NS(=O)(=O)N1CCN(c2ccc(Cl)cc2)CC1)C(=O)NO
Temperature: 25 °C
Yield: 43.5 %

Procedure:
Trimethylsilyl iodide (0.026 ml, 0.19 mmol) was added to a solution of N-hydroxy-6-(benzyloxycarbonyl)amino-2-(R)-{[4-(4-chlorophenyl)piperazine-1-sulfonyl]amino}hexanoamide (103 mg, 0.19 mmol) [prepared as described in Example 17, Step 3] in acetonitrile (2 ml) at 0° C. The reaction mixture was allowed to warm to RT, and additional trimethylsilyl iodide (0.47 mmol, 0.065 ml) was added in 0.5 equiv. portions over 2.5 h. Methanol (1.0 ml) was added and the reaction mixture was concentrated in vacuo. The residue was chromatographed (SiO2, 2%-10% methanol/methylene chloride) to give N-hydroxy-6-amino-2-(R)-{[4-(4-chlorophenyl)piperazine-1-sulfonyl]amino}hexanoamide (43.5%) as a tan solid.
Reaction SMILES: C(OC(=O)[NH:7][CH2:8][CH2:9][S:10]([C:13]1[C:14]2[CH:15]=[CH:16][N:17]=[CH:18][C:19]=2[CH:20]=[C:21]([C:23]2[CH:28]=[CH:27][C:26]([O:29]C)=[CH:25][CH:24]=2)[CH:22]=1)(=[O:12])=[O:11])(C)(C)C.B(Br)(Br)Br.C(O)C>ClCCl>[NH2:7][CH2:8][CH2:9][S:10]([C:13]1[CH:22]=[C:21]([C:23]2[CH:28]=[CH:27][C:26]([OH:29])=[CH:25][CH:24]=2)[CH:20]=[C:19]2[C:14]=1[CH:15]=[CH:16][N:17]=[CH:18]2)(=[O:11])=[O:12]
Reactant: COc1ccc(-c2cc(S(=O)(=O)CCNC(=O)OC(C)(C)C)c3ccncc3c2)cc1
Agent: BrB(Br)Br
Solvent: ClCCl
Solvent: CCO
Product: NCCS(=O)(=O)c1cc(-c2ccc(O)cc2)cc2cnccc12
Temperature: 0 °C
Yield: 55.1 %

Procedure:
To {2-[7-(4-methoxy-phenyl)-isoquinoline-5-sulfonyl]-ethyl}-carbamic acid tert-butyl ester (25.00 g, 56.49 mmol) in dichloromethane (1 L) at 0° C. add BBr3 (1.0 M in dichloromethane, 200 mL, 200 mmol) over 40 min with vigorous overhead stirring. Remove the cooling bath and stir at room temperature overnight. Cool to 0° C. and add methanol (500 mL) dropwise over 1 h. Filter the resulting slurry, rinse the flask with dichloromethane (100 mL) and wash the solids with the rinse. Wash the solids with additional dichloromethane (150 mL) and dry under vacuum filtration. Slurry the solids in methanol (400 mL) with stirring, then concentrate under vacuum to a thin paste. Add additional methanol (400 mL) and further slurry the solids with stirring. Concentrate the slurry under vacuum to dryness, and dry the solids overnight under vacuum. Pulverize the solids to a powder and slurry in methanol (1 L). Add Amberlyst® A-21 resin (75 g) and stir until the powder is dissolved. Filter the resin, slurry the filtered resin in methanol (220 mL) and filter the resin again, combining the filtrates. Wash the filtered resin with methanol (100 mL) and add this wash to the filtrates. Combine the filtrates with ethanol (200 mL) and concentrate the mixture under vacuum to a volume of about 200 mL to afford a slurry. Add ethanol (400 mL), warm the slurry to 50° C. for about 15 min, then concentrate under vacuum to a volume of about 200 mL. Cool the slurry to room temperature, filter and rinse the filter cake with ethanol (2×15 mL), then dry under vacuum to afford the title compound (10.22 g, 55%) as a tan solid. Mass spectrum (LCMS) m/z=329.0 (M+H+).
Reaction SMILES: [C:1]([O:4][C:5]1[CH:10]=[CH:9][C:8]([C:11](Cl)=[O:12])=[CH:7][CH:6]=1)(=[O:3])[CH3:2].C(N(CC)CC)C.[CH3:21][S:22][C:23]1[N:24]=[C:25]([NH2:28])[S:26][CH:27]=1>C1COCC1>[C:1]([O:4][C:5]1[CH:10]=[CH:9][C:8]([C:11](=[O:12])[NH:28][C:25]2[S:26][CH:27]=[C:23]([S:22][CH3:21])[N:24]=2)=[CH:7][CH:6]=1)(=[O:3])[CH3:2]
Reactant: CSc1csc(N)n1
Reactant: CC(=O)Oc1ccc(C(=O)Cl)cc1
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: CSc1csc(NC(=O)c2ccc(OC(C)=O)cc2)n1
Temperature: 25 °C
Yield: 109 %

Procedure:
Into a solution of 510 (0.815 g, 4.10 mmol) and dry THF (20.0 mL) was added a solution of triethylamine (0.572 mL, 4.10 mmol) and dry THF (5.00 mL), followed by a solution of 508 (0.500 g, 3.42 mmol) dissolved in dry THF (15.0 mL). The reaction was stirred at room temperature. After stirring overnight, the reaction was concentrated in vacuo. The residue was partitioned between a saturated aqueous sodium bicarbonate and dichloromethane. The dichloromethane layer was washed a second time with the saturated sodium bicarbonate solution and than twice with aq. 1 M HCl. The dichloromethane layer was dried over anhydrous magnesium sulfate and concentrated in vacuo to give crude 512 (1.15 g, >100%) as a brown solid. The crude product was suspended in diethyl ether, stirred and filtered. The filter pad was washed with ether several times, and dried in vacuo to give 512 (0.692 g, 63%) as a light brown solid.
Reaction SMILES: [CH3:1][O:2][CH2:3][CH:4]([OH:21])[C@@H:5]([NH:10]C(OCC1C=CC=CC=1)=O)[CH2:6][CH:7]([CH3:9])[CH3:8].[ClH:22]>CO.[Pd]>[ClH:22].[CH3:1][O:2][CH2:3][CH:4]([OH:21])[C@@H:5]([NH2:10])[CH2:6][CH:7]([CH3:9])[CH3:8]
Reactant: COCC(O)[C@H](CC(C)C)NC(=O)OCc1ccccc1
Agent: [Pd]
Agent: Cl
Solvent: CO
Product: COCC(O)[C@@H](N)CC(C)C

Procedure:
To a solution of 94 mg of the ether compound obtained in 10 ml of methanol was added 0.16 ml of a 2N-hydrochloric acid, and the mixture was hydrogenated over 10 mg of a 10% palladium charcoal under hydrogen atmosphere. After filtration of the catalyst, the filtrate was evaporated under reduced pressure to obtain 54 mg of (2RS, 3S)-3-amino-2-hydroxy-5-methylhexyl methyl ether hydrochloride as a colorless viscous oil.
Reaction SMILES: [C:1]1([CH2:7][O:8][C:9]([NH:11][C@H:12]([C:20]([OH:22])=O)[CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[O:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C[N:24]1CCOCC1.C(OC(Cl)=O)C(C)C>O1CCCC1>[C:1]1([CH2:7][O:8][C:9]([NH:11][C@H:12]([C:20]([NH2:24])=[O:22])[CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[O:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: O=C(N[C@@H](Cc1ccccc1)C(=O)O)OCc1ccccc1
Reactant: CN1CCOCC1
Agent: CC(C)COC(=O)Cl
Solvent: C1CCOC1
Product: NC(=O)[C@H](Cc1ccccc1)NC(=O)OCc1ccccc1
Reaction time: 0.02 h

Procedure:
An 18 g portion of Nα -[(phenylmethoxy)carbonyl]-L-phenylalanine and 6.6 ml of N-methylmorpholine were dissolved in 150 ml of tetrahydrofuran and stirred at 31 10° C. as 8.04 ml of isobutylchloroformate was added. After 1 minute, ammonia gas was bubbled through the mixture until it was saturated. The mixture was stirred an additional 30 minutes and then poured into ice-water. The white solid was collected, giving 16.76 g of the desired compound, mp 164°-165° C.
Reaction SMILES: Br[C:2]1[C:11]2[NH:10][C:9](=[O:12])[C:8](=[O:13])[NH:7][C:6]=2[C:5]2[CH2:14][CH:15]([NH:17][C:18](=[O:20])[CH3:19])[CH2:16][C:4]=2[CH:3]=1.C([O-])(=O)C.[K+]>CN(C)C=O.[Pd]>[O:13]=[C:8]1[NH:7][C:6]2[C:5]3[CH2:14][CH:15]([NH:17][C:18](=[O:20])[CH3:19])[CH2:16][C:4]=3[CH:3]=[CH:2][C:11]=2[NH:10][C:9]1=[O:12]
Reactant: CC(=O)NC1Cc2cc(Br)c3[nH]c(=O)c(=O)[nH]c3c2C1
Agent: [Pd]
Agent: CC(=O)[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CC(=O)NC1Cc2ccc3[nH]c(=O)c(=O)[nH]c3c2C1
Reaction time: 0.12 h
Yield: 96.4 %

Procedure:
N-(5-Bromo-2,3-dioxo-2,3,4,7,8,9-hexahydro-1H-cyclopenta[f]quinoxalin-8-yl)-acetamide (1 g, 3 mmol) was dissolved in dimethylformamide (75 mL) and treated with potassium acetate (0.33 g) and 20% palladium on carbon (0.2 g) and shaken on a Parr apparatus under a hydrogen atmosphere (51 psi) for 7 min. The catalyst was removed by filtration, the filtrate evaporated and the residue triturated in water. The resulting solid was collected by filtration and dried in vacuo to give the debrominated product (0.75 g) in 98% yield. Anal. Calc'd for C13H13N3O3.1.7 H2 O: C, 53.85; H, 5.70; N, 14.49. Found: C, 53.87; H, 5.04; N, 14.15.
Reaction SMILES: Cl[C:2]1[C:7]([C:8]#[N:9])=[C:6]([NH:10][CH2:11][CH2:12][OH:13])[N:5]=[C:4]([NH:14][CH2:15][CH2:16][OH:17])[N:3]=1.[OH:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=1[N:25]1[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]1.C(N(C(C)C)C(C)C)C>O1CCOCC1>[OH:17][CH2:16][CH2:15][NH:14][C:4]1[N:5]=[C:6]([NH:10][CH2:11][CH2:12][OH:13])[C:7]([C:8]#[N:9])=[C:2]([N:28]2[CH2:27][CH2:26][N:25]([C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][C:19]=3[OH:18])[CH2:30][CH2:29]2)[N:3]=1
Reactant: Oc1ccccc1N1CCNCC1
Reactant: N#Cc1c(Cl)nc(NCCO)nc1NCCO
Solvent: CCN(C(C)C)C(C)C
Solvent: C1COCCO1
Product: N#Cc1c(NCCO)nc(NCCO)nc1N1CCN(c2ccccc2O)CC1

Procedure:
In analogy to the procedure described in example 20b, 4-chloro-2,6-bis-(2-hydroxy-ethylamino)-pyrimidine-5-carbonitrile was treated with 1-(2-hydroxy-phenyl)-piperazine in dioxane in the presence of N-ethyl-diisopropylamine at 60° C. to yield 2,4-bis-(2-hydroxy-ethylamino)-6-[4-(2-hydroxy-phenyl)-piperazin-1-yl]-pyrimidine-5-carbonitrile as a white lyophilisate; MS: [M+H]+=399.
Reaction SMILES: [CH:1]1[C:13]2[NH:12][C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1.[Br:14][C:15]1[CH:20]=[CH:19][CH:18]=[C:17](Br)[CH:16]=1.C([O-])([O-])=O.[K+].[K+]>[Cu].CN(C)C=O>[Br:14][C:15]1[CH:16]=[C:17]([N:12]2[C:11]3[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=3[C:5]3[C:13]2=[CH:1][CH:2]=[CH:3][CH:4]=3)[CH:18]=[CH:19][CH:20]=1
Reactant: c1ccc2c(c1)[nH]c1ccccc12
Reactant: Brc1cccc(Br)c1
Agent: [Cu]
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: Brc1cccc(-n2c3ccccc3c3ccccc32)c1
Temperature: 130 °C
Yield: 71 %

Procedure:
(see Kido, J.; Su, S. -J.; Sasabe, H.; Takeda, T.; Chem. Mater. 2008, 20(5), 1691-1693, which is incorporated by reference herein for its relevant teachings) was prepared as follows: a mixture of carbazole (4.000 g, 23.92 mmol), 1,3-dibromobenzene (14.11 g, 59.81 mmol), K2CO3 (9.919 g, 71.77 mmol), copper powder (4.561 g, 71.77 mmol) and anhydrous N,N-dimethylformamide (DMF) (120 mL) was degassed with argon for 1 h. while stirring. The reaction mixture was then maintained under argon at 130° C. while stirring for 4 days until TLC (SiO2, 4:1 hexanes-dichloromethane) indicated consumption of the starting material. Upon cooling to RT, about 300 mL dichloromethane was added, the crude mixture filtered, the filtrant wash with an additional 200 mL dichloromethane, and the filtrate concentrated in vacuo. The resulting residue was then purified by flash chromatography (SiO2, hexanes) to yield Compound 3 (5.47 g, 71%) as a colorless oil.
Reaction SMILES: [CH:1]1([O:7][C:8]2[CH:13]=[CH:12][C:11]([C:14]3[C:15]([NH2:20])=[N:16][CH:17]=[CH:18][N:19]=3)=[CH:10][CH:9]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[H-].[Na+].Cl[CH2:24][CH2:25][S:26](Cl)(=[O:28])=[O:27].O>C1COCC1>[CH:1]1([O:7][C:8]2[CH:9]=[CH:10][C:11]([C:14]3[C:15]4=[N:20][S:26](=[O:28])(=[O:27])[CH2:25][CH2:24][N:16]4[CH:17]=[CH:18][N:19]=3)=[CH:12][CH:13]=2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1
Reactant: O=S(=O)(Cl)CCCl
Reactant: Nc1nccnc1-c1ccc(OC2CCCCC2)cc1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Product: O=S1(=O)CCN2C=CN=C(c3ccc(OC4CCCCC4)cc3)C2=N1
Temperature: 80 °C
Reaction time: 3 h
Yield: 83.2 %

Procedure:
A mixture of 3-[4-(cyclohexyloxy)phenyl]pyrazin-2-amine (470 mg) in THF (dry) (25.00 mL) was added to a mixture of NaH (60%, 349 mg) and 2-chloroethanesulfonyl chloride (853 mg) in THF (dry) (25 mL) at room temperature. The mixture was stirred at room temperature overnight and 80° C. for 3 hr. Water was added and THF was removed in vacuo. A precipitate was collected by filtration and washed with water-Et2O to give the title compound (522 mg) as a yellow solid. The solid was crystallized from CH3CN-IPE to give a yellow solid.
Reaction SMILES: COC[O:4][CH2:5][C:6]1[C:11]([CH3:12])=[CH:10][N:9]=[CH:8][C:7]=1Br.[CH3:14][O:15][C:16]1[CH:17]=[C:18]2[C:23](=[CH:24][C:25]=1[O:26][CH3:27])[CH2:22][CH2:21][C:20]([N+:28]([O-:30])=[O:29])=[CH:19]2>>[CH3:27][O:26][C:25]1[CH:24]=[C:23]2[C:18](=[CH:17][C:16]=1[O:15][CH3:14])[C@@H:19]([C:7]1[CH:8]=[N:9][CH:10]=[C:11]([CH3:12])[C:6]=1[CH2:5][OH:4])[C@H:20]([N+:28]([O-:30])=[O:29])[CH2:21][CH2:22]2
Reactant: COCOCc1c(C)cncc1Br
Reactant: COc1cc2c(cc1OC)CCC([N+](=O)[O-])=C2
Product: COc1cc2c(cc1OC)[C@@H](c1cncc(C)c1CO)[C@H]([N+](=O)[O-])CC2

Procedure:
The compound of step 14c was condensed with 1,2-dihydro-6,7-dimethoxy-3-nitronaphthalene according to the procedure of Example 13c. The protecting methoxymethyl group was removed from the intermediate by a standard hydrolysis method (HCl, ethanol).
Reaction SMILES: [F:1][C:2]([F:34])([F:33])[C:3]1[CH:4]=[C:5]([C@H:13]([O:15][C@H:16]2[O:24][CH2:23][C@@H:19]3[CH2:20][NH:21][CH2:22][C@H:18]3[C@@H:17]2[C:25]2[CH:30]=[CH:29][C:28]([F:31])=[CH:27][C:26]=2[CH3:32])[CH3:14])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.C1C(=O)N([I:42])C(=O)C1>FC(F)(F)C(O)=O>[F:34][C:2]([F:1])([F:33])[C:3]1[CH:4]=[C:5]([C@H:13]([O:15][C@H:16]2[O:24][CH2:23][C@@H:19]3[CH2:20][NH:21][CH2:22][C@H:18]3[C@@H:17]2[C:25]2[CH:30]=[C:29]([I:42])[C:28]([F:31])=[CH:27][C:26]=2[CH3:32])[CH3:14])[CH:6]=[C:7]([C:9]([F:12])([F:10])[F:11])[CH:8]=1
Reactant: O=C1CCC(=O)N1I
Reactant: Cc1cc(F)ccc1[C@@H]1[C@@H](O[C@H](C)c2cc(C(F)(F)F)cc(C(F)(F)F)c2)OC[C@@H]2CNC[C@H]21
Solvent: O=C(O)C(F)(F)F
Product: Cc1cc(F)c(I)cc1[C@@H]1[C@@H](O[C@H](C)c2cc(C(F)(F)F)cc(C(F)(F)F)c2)OC[C@@H]2CNC[C@H]21

Procedure:
A solution of (3aS,6R,7R,7aR)-6-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy}-7-(4-fluoro-2-methylphenyl)octahydropyrano[3,4-c]pyrrole (55.8 mg, 0.12 mmol) and NIS (53 mg, 0.23 mmol) in 2 mL trifluoroacetic acid was stirred at rt for 40 min. Volatiles were removed. The crude was purified by reverse phase HPLC to afford the title compound.
Reaction SMILES: Cl[C:2](Cl)([O:4][C:5](=[O:11])[O:6][C:7](Cl)(Cl)Cl)Cl.C(N([CH2:18][CH3:19])CC)C>>[C:5]([C:18]1([CH3:19])[CH2:7][O:6][C:5](=[O:11])[O:4][CH2:2]1)([O:4][CH3:2])=[O:6]
Reactant: CCN(CC)CC
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Product: COC(=O)C1(C)COC(=O)OC1

Procedure:
As set out hereinabove, the binder component of the dispersion of the invention is an organic polycarbonate polymer. The resulting polymer of the polymerization of 5-carbomethoxy-5-methyl-1,3-dioxan-2-one may be used as a component of the polymer binder. The polycarbonate polymer of 5-carbomethoxy-5-methyl-1,3-dioxan-2-one may be prepared as disclosed in Weilandt, K. D., Keul, H. and Hocker, H., Macromol. Chem. Phys. 197, 3851-3868 (1996). 5-Carbomethoxy-5-methyl-1,3-dioxan-2-one may be prepared via the reaction of 2,2-bis(hydroxymethyl)propionic acid with methanol to give methyl 2,2-bis(hydroxymethyl)propionate, which was then reacted with triphosgene in the presence of triethylamine to afford the desired product, 5-carbomethoxy-5-methyl-1,3-dioxan-2-one, as a white solid.
Reaction SMILES: [NH2:1][C:2]1[C:3]([C:14]([NH2:16])=O)=[N:4][CH:5]=[C:6]([N:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)[CH:7]=1.P(Cl)(Cl)(Cl)=O>C(#N)C>[NH2:1][C:2]1[C:3]([C:14]#[N:16])=[N:4][CH:5]=[C:6]([N:8]2[CH2:9][CH2:10][O:11][CH2:12][CH2:13]2)[CH:7]=1
Reactant: NC(=O)c1ncc(N2CCOCC2)cc1N
Solvent: O=P(Cl)(Cl)Cl
Solvent: CC#N
Product: N#Cc1ncc(N2CCOCC2)cc1N
Temperature: 25 °C

Procedure:
A stirred solution of 3-amino-5-morpholinopicolinamide (0.35 g, 1.57 mmol) in acetonitrile (10 mL) was treated with phosphorus oxychloride (0.29 mL, 3.15 mmol). The reaction was heated at reflux for 1 h. After this time the reaction was cooled to rt and evaporated in vacuo. The residue was dissolved in Et2O (10 mL) and treated with 4.0M HCl in dioxane (0.2 mL). The resulting solid was filtered and dried under vacuum to give 3-amino-5-morpholinopicolinonitrile. Mass Spectrum (ESI) m/e=205.2 (M+1).
Reaction SMILES: [Br:1][C:2]1[CH:14]=[CH:13][C:5]([CH:6]=[C:7]2[CH2:11][CH2:10][CH2:9][N:8]2[CH3:12])=[CH:4][CH:3]=1>C(O)C.[Pt].[H][H]>[Br:1][C:2]1[CH:14]=[CH:13][C:5]([CH2:6][CH:7]2[CH2:11][CH2:10][CH2:9][N:8]2[CH3:12])=[CH:4][CH:3]=1
Reactant: [H][H]
Reactant: CN1CCCC1=Cc1ccc(Br)cc1
Agent: [Pt]
Solvent: CCO
Product: CN1CCCC1Cc1ccc(Br)cc1

Procedure:
Hydrogenate 21.5 g of 2-(4-bromobenzylidene)-1-methylpyrrolidine in 400 ml of ethanol with platinum on activated charcoal/hydrogen. Filter out the catalyst, concentrate the filtrate and distil the residue to obtain 18.5 g (85% of theory) of the title compound (b.p. 70° at 0.001 mm of Hg).