Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][Si:2]([CH3:38])([CH3:37])[CH2:3][CH2:4][O:5][CH2:6][N:7]([CH2:29][O:30][CH2:31][CH2:32][Si:33]([CH3:36])([CH3:35])[CH3:34])[C:8]1[N:13]2[N:14]=[CH:15][CH:16]=[C:12]2[N:11]=[C:10]([CH2:17][CH:18]2[CH2:23][CH2:22][CH:21]([C:24]([O:26][CH2:27][CH3:28])=[O:25])[CH2:20][CH2:19]2)[CH:9]=1.[I:39]N1C(=O)CCC1=O>CC#N>[CH3:34][Si:33]([CH3:36])([CH3:35])[CH2:32][CH2:31][O:30][CH2:29][N:7]([CH2:6][O:5][CH2:4][CH2:3][Si:2]([CH3:1])([CH3:37])[CH3:38])[C:8]1[N:13]2[N:14]=[CH:15][C:16]([I:39])=[C:12]2[N:11]=[C:10]([CH2:17][CH:18]2[CH2:23][CH2:22][CH:21]([C:24]([O:26][CH2:27][CH3:28])=[O:25])[CH2:20][CH2:19]2)[CH:9]=1
Reactant: O=C1CCC(=O)N1I
Reactant: CCOC(=O)C1CCC(Cc2cc(N(COCC[Si](C)(C)C)COCC[Si](C)(C)C)n3nccc3n2)CC1
Solvent: CC#N
Product: CCOC(=O)C1CCC(Cc2cc(N(COCC[Si](C)(C)C)COCC[Si](C)(C)C)n3ncc(I)c3n2)CC1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a 100 mL round-bottom flask was charged ethyl 4-((7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)pyrazolo[1,5-a]pyrimidin-5-yl)methyl)cyclohexanecarboxylate (Int-4i, 2.64 g, 4.69 mmol) and N-iodosuccinimide (1.16 g, 5.16 mmol). To this mixture was added MeCN (40 mL). The resulting solution was stirred at room temperature overnight. After 18 hours, the reaction was reduced in vacuo and the residue was purified via silica gel chromatography to yield the title compound. Yield=2.94 g.
Reaction SMILES: C([O:5][C:6](=[O:17])[CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([N+:14]([O-:16])=[O:15])[CH:9]=1)(C)(C)C.Br[CH2:19][CH2:20][CH2:21]Br>>[N+:14]([C:10]1[CH:9]=[C:8]([C:7]2([C:6]([OH:5])=[O:17])[CH2:21][CH2:20][CH2:19]2)[CH:13]=[CH:12][CH:11]=1)([O-:16])=[O:15]
Reactant: BrCCCBr
Reactant: CC(C)(C)OC(=O)Cc1cccc([N+](=O)[O-])c1
Product: O=C(O)C1(c2cccc([N+](=O)[O-])c2)CCC1

Procedure:
Using 3-nitrophenylacetic acid t-butyl ester as a starting material and also using 1,3-dibromopropane (1 eq.) as a reagent, the same procedures of Examples 1a and 1b gave 1-(3-nitrophenyl)cyclobutanecarboxylic acid.
Reaction SMILES: [CH3:1][C:2]1[C:6]2[C:7](=[O:19])[N:8]([CH2:11][CH2:12][N:13]3[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]3)[CH2:9][CH2:10][C:5]=2[NH:4][C:3]=1[CH:20]=O.[F:22][C:23]1[CH:24]=[C:25]([C:29]2[CH:37]=[CH:36][CH:35]=[C:34]3[C:30]=2[CH2:31][C:32](=[O:38])[NH:33]3)[CH:26]=[CH:27][CH:28]=1>>[F:22][C:23]1[CH:24]=[C:25]([C:29]2[CH:37]=[CH:36][CH:35]=[C:34]3[C:30]=2[C:31](=[CH:20][C:3]2[NH:4][C:5]4[CH2:10][CH2:9][N:8]([CH2:11][CH2:12][N:13]5[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18]5)[C:7](=[O:19])[C:6]=4[C:2]=2[CH3:1])[C:32](=[O:38])[NH:33]3)[CH:26]=[CH:27][CH:28]=1
Reactant: Cc1c(C=O)[nH]c2c1C(=O)N(CCN1CCCCC1)CC2
Reactant: O=C1Cc2c(cccc2-c2cccc(F)c2)N1
Product: Cc1c(C=C2C(=O)Nc3cccc(-c4cccc(F)c4)c32)[nH]c2c1C(=O)N(CCN1CCCCC1)CC2
Yield: 60.7 %

Procedure:
The title compound was prepared under the same conditions as described in Example 25 with 3-methyl-4-oxo-5-(2-piperidin-1-yl-ethyl)-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridine-2-carbaldehyde and 4-(3-fluoro-phenyl)-1,3-dihydro-indol-2-one (prepared according to WO2002055517) as starting materials to give 2-[4-(3-fluoro-phenyl)-2-oxo-1,2-dihydro-indol-3-ylidenemethyl]-3-methyl-5-(2-piperidin-1-yl-ethyl)-1,5,6,7-tetrahydro-pyrrolo[3,2-c]pyridin-4-one (63 mg, 60.7%) as an orange solid.
Reaction SMILES: [CH:1]1[C:6]2[N:7]=[C:8]3[CH:15]=[CH:14][CH:13]=[CH:12][N:9]3[CH2:10][O:11][C:5]=2[CH:4]=[CH:3][CH:2]=1.[CH3:16][N:17]1[C:21](=[O:22])[CH:20]=[CH:19][C:18]1=[O:23]>C1(C)C(C)=CC=CC=1>[CH3:16][N:17]1[C:21](=[O:22])[CH:20]2[CH:19]([CH:15]3[CH2:14][CH2:13][CH:12]2[N:9]2[CH2:10][O:11][C:5]4[CH:4]=[CH:3][CH:2]=[CH:1][C:6]=4[N:7]=[C:8]32)[C:18]1=[O:23]
Reactant: CN1C(=O)C=CC1=O
Reactant: C1=CC2=Nc3ccccc3OCN2C=C1
Solvent: Cc1ccccc1C
Product: CN1C(=O)C2C3CCC(C2C1=O)N1COc2ccccc2N=C31
Temperature: 25 °C
Reaction time: 5 h
Yield: 78.1 %

Procedure:
A mixture of 6H-pyrido[1,2-c][1,3,5]benzoxadiazepine (1.98 g) and N-methylmaleimide (1.68 g) in 50 ml of xylene is heated under reflux conditions for 23 hours. The reaction mixture is allowed to cool to room temperature and then allowed to stand in a refrigerator for 5 hours. The crude product is collected, washed with xylene and dried in vacuo for about 16 hours at room temperature and for 6 hours at 110° C to give 2.43 g of the title compound, melting point 252°-253° C.
Reaction SMILES: C([O:8][C:9]1[CH:18]=[CH:17][C:16]2[N:15]=[C:14](Cl)[C:13]3[N:20]=[C:21]([CH2:27][O:28][CH3:29])[N:22]([CH2:23][CH:24]([CH3:26])[CH3:25])[C:12]=3[C:11]=2[CH:10]=1)C1C=CC=CC=1.[OH-].[Na+].[BrH:32]>C(O)(=O)C>[Br:32][C:14]1[C:13]2[N:20]=[C:21]([CH2:27][O:28][CH3:29])[N:22]([CH2:23][CH:24]([CH3:26])[CH3:25])[C:12]=2[C:11]2[CH:10]=[C:9]([OH:8])[CH:18]=[CH:17][C:16]=2[N:15]=1
Reactant: Br
Reactant: COCc1nc2c(Cl)nc3ccc(OCc4ccccc4)cc3c2n1CC(C)C
Agent: [Na+]
Agent: [OH-]
Solvent: CC(=O)O
Product: COCc1nc2c(Br)nc3ccc(O)cc3c2n1CC(C)C

Procedure:
8-Benzyloxy-4-chloro-1-(2-methylpropyl)-2-methoxymethyl-1H-imidazo[4,5-c]quinoline (2.73 g, 6.65 mmol) was stirred for 1 hour in 25 mL of 30% hydrogen bromide in acetic acid at 65° C. The reaction was cooled in an ice bath and aqueous NaOH (50%) was added to adjust the pH to 7. The precipitate was recovered by filtration and air dried to provide 2.75 g of 4-bromo-1-(2-methylpropyl)-2-methoxymethyl-1H-imidazo[4,5-c]quinolin-8-ol as a brown solid.
Reaction SMILES: [CH2:1]1[CH:5]2[CH2:6][NH:7][CH2:8][CH:4]2[CH2:3][N:2]1[C:9]1[CH:10]=[CH:11][C:12]2[N:13]([C:15]([C:18]([F:21])([F:20])[F:19])=[N:16][N:17]=2)[N:14]=1.[F:22][C:23]1[CH:24]=[C:25]([CH:28]=[CH:29][CH:30]=1)[CH:26]=O>>[F:22][C:23]1[CH:24]=[C:25]([CH2:26][N:7]2[CH2:8][CH:4]3[CH:5]([CH2:1][N:2]([C:9]4[CH:10]=[CH:11][C:12]5[N:13]([C:15]([C:18]([F:20])([F:21])[F:19])=[N:16][N:17]=5)[N:14]=4)[CH2:3]3)[CH2:6]2)[CH:28]=[CH:29][CH:30]=1
Reactant: FC(F)(F)c1nnc2ccc(N3CC4CNCC4C3)nn12
Reactant: O=Cc1cccc(F)c1
Product: Fc1cccc(CN2CC3CN(c4ccc5nnc(C(F)(F)F)n5n4)CC3C2)c1

Procedure:
Reductive amination of 6-(hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)-3-(trifluoromethyl)-[1,2,4]triazolo[4,3-b]pyridazine with 3-fluorobenzaldehyde was carried out according to General Synthetic Method 10. The crude product was purified by hplc using a Waters XBridge Prep C18 OBD column, 5μ silica, 30 mm diameter, 100 mm length eluted with decreasingly polar mixtures of water (containing 0.1% aqueous ammonia) and acetonitrile as eluents to give 6-[2-[(3-fluorophenyl)methyl]-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-5-yl]-3-(trifluoromethyl)-[1,2,4]triazolo[4,3-b]pyridazine.
Reaction SMILES: [H-].[H-].[H-].[H-].[Li+].[Al+3].C([O:9][C:10](=O)[CH:11]([CH2:17][C:18]([F:21])([F:20])[F:19])[CH2:12][C:13]([F:16])([F:15])[F:14])C>CCOCC>[F:14][C:13]([F:15])([F:16])[CH2:12][CH:11]([CH2:17][C:18]([F:19])([F:20])[F:21])[CH2:10][OH:9]
Reactant: CCOC(=O)C(CC(F)(F)F)CC(F)(F)F
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: CCOCC
Product: OCC(CC(F)(F)F)CC(F)(F)F
Reaction time: 1 h
Yield: 40.9 %

Procedure:
To a suspension of LAH (1.0 g) in Et2O (100 mL) at 25° C. was added slowly 4,4,4-trifluoro-2-(2,2,2-trifluoroethyl)-butyric acid ethyl ester (5.0 g, 19.8 mmol). The resulting mixture was stirred at reflux for 4 h. The cooled reaction mixture was quenched sequentially with water (1.0 mL), 15% NaOH in water (1.0 mL) and water (3.0 mL). After the resulting mixture was allowed to stir at 25° C. for 17 h, Na2SO4 (20 g) was added and stirring at 25° C. continued for 1 h. The resulting suspension was filtered through a pad of the Celite® reagent and Na2SO4. The filtrate was distilled to remove all solvents to afford the desired product as a colorless liquid (1.7 g, 41%). Mass Spectrum (−ESI): 269 [M+OAc]−
Reaction SMILES: C([N:9]1[C:17]2[CH:16]=[CH:15][C:14]([C:18]#[N:19])=[C:13]3[CH2:20][C@@H:21]([N:23]([CH2:27][CH2:28][CH3:29])[CH2:24][CH2:25][CH3:26])[CH2:22][C@@H:11]([C:12]=23)[CH2:10]1)(=O)C1C=CC=CC=1.C([Li])CCC>>[C:18]([C:14]1[CH:15]=[CH:16][C:17]2[NH:9][CH2:10][C@H:11]3[CH2:22][C@H:21]([N:23]([CH2:27][CH2:28][CH3:29])[CH2:24][CH2:25][CH3:26])[CH2:20][C:13]=1[C:12]=23)#[N:19]
Reactant: CCCN(CCC)[C@@H]1Cc2c(C#N)ccc3c2[C@H](C1)CN3C(=O)c1ccccc1
Agent: [Li]CCCC
Product: CCCN(CCC)[C@@H]1Cc2c(C#N)ccc3c2[C@@H](CN3)C1
Yield: 86.9 %

Procedure:
The procedure of Example 4F was followed using 2.5 g (6.5 mmol) of (2aS,4S)-1-benzoyl-6-cyano-4-(di-n-propylamino)-1,2,2a,3,4,5-hexahydrobenz[cd]-indole and 8.1 ml (13 mmol) n-butyl lithium to provide 1.6 g of an oil. Chromatography of the oil over silica gel with EtOAc as eluent gave 1 g (54%) of product as an oil.
Reaction SMILES: C([O:3][P:4]([CH2:9][CH2:10][NH:11][CH2:12][C:13]([CH3:36])=[CH:14][CH2:15][C:16]1[C:17]([O:29]CC[Si](C)(C)C)=[C:18]2[C:22](=[C:23]([CH3:27])[C:24]=1[O:25][CH3:26])[CH2:21][O:20][C:19]2=[O:28])(=[O:8])[O:5]CC)C.C[Si](Br)(C)C.N1[C:47]([CH3:48])=[CH:46][CH:45]=[CH:44][C:43]=1[CH3:49]>C(#N)C>[CH2:49]([N:11]([CH2:12][C:13]([CH3:36])=[CH:14][CH2:15][C:16]1[C:17]([OH:29])=[C:18]2[C:22](=[C:23]([CH3:27])[C:24]=1[O:25][CH3:26])[CH2:21][O:20][C:19]2=[O:28])[CH2:10][CH2:9][P:4](=[O:8])([OH:5])[OH:3])[C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1
Reactant: CCOP(=O)(CCNCC(C)=CCc1c(OC)c(C)c2c(c1OCC[Si](C)(C)C)C(=O)OC2)OCC
Reactant: Cc1cccc(C)n1
Agent: C[Si](C)(C)Br
Solvent: CC#N
Product: COc1c(C)c2c(c(O)c1CC=C(C)CN(CCP(=O)(O)O)Cc1ccccc1)C(=O)OC2
Temperature: 25 °C
Reaction time: 1 h
Yield: 96.4 %

Procedure:
A solution of (2-{4-[6-methoxy-7-methyl-3-oxo-4-(2-trimethylsilanyl-ethoxy)-1,3-dihydro-isobenzofuran-5-yl]-2-methyl-but-2-enylamino}-ethyl)-phosphonic acid diethyl ester (15 mg, 0.024 mmol) in acetonitrile (0.5 mL) was treated with TMSBr (31 μL, 0.24 mmol) and 2,6-lutidine (28 μL, 0.24 mmol). The solution was stirred at ambient temperature for 1 hour, when it was quenched with methanol. The solvent was removed under reduced pressure and the residue was purified by RP HPLC using a C18 column with a gradient of H2O, 0.1% TFA-acetonitrile, 0.1% TFA to provide 11 mg of the product (93%) as a white solid. 1H NMR (300 MHz, CD3OD) δ 1.89 (s, 3H), 2.03-2.15 (m, 2H), 2.14 (s, 3H), 3.30-3.47 (m, 2H), 3.50 (br s, 2H), 3.62 (br s, 2H), 3.79 (s, 3H), 4.28 (s, 2H), 5.23 (s, 2H), 5.76 (br s, 1H), 7.46 (br s, 5H) ppm; 31P (121.4 MHz, CDCl3) δ 20.1 ppm; MS (m/z) 476.3 [M+H]+, 498.3 [M+Na]+.
Reaction SMILES: [CH2:1]([N:5]1[C:13]2[N:12]=[CH:11][N:10]([CH2:14][CH2:15][CH2:16][CH3:17])[C:9]=2[C:8](=[O:18])[NH:7][C:6]1=[O:19])[CH2:2][CH2:3][CH3:4].Br[CH2:21][CH2:22][CH2:23][P:24]([O:29][CH2:30][CH3:31])(=[O:28])[O:25][CH2:26][CH3:27]>>[CH2:1]([N:5]1[C:13]2[N:12]=[CH:11][N:10]([CH2:14][CH2:15][CH2:16][CH3:17])[C:9]=2[C:8](=[O:18])[N:7]([CH2:21][CH2:22][CH2:23][P:24](=[O:28])([O:29][CH2:30][CH3:31])[O:25][CH2:26][CH3:27])[C:6]1=[O:19])[CH2:2][CH2:3][CH3:4]
Reactant: CCCCn1cnc2c1c(=O)[nH]c(=O)n2CCCC
Reactant: CCOP(=O)(CCCBr)OCC
Product: CCCCn1cnc2c1c(=O)n(CCCP(=O)(OCC)OCC)c(=O)n2CCCC

Procedure:
The title substance was prepared from 0.02 mol of 3,7-dibutylxanthine and 0.022 mol of diethyl 3-bromopropanephosphonate analogously to Example 23 and chromatographed on silica gel (eluent: dichloromethane/methanol 20:1).
Reaction SMILES: Br[C:2]1[CH:18]=[CH:17][CH:16]=[CH:15][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][N:8]=[C:7]([C:11]([F:14])([F:13])[F:12])[CH:6]=1.[F:19][C:20]1[CH:25]=[C:24](B2OC(C)(C)C(C)(C)O2)[CH:23]=[CH:22][C:21]=1[C:35]1[CH:36]=[N:37][C:38]([NH2:41])=[N:39][CH:40]=1>>[F:19][C:20]1[CH:25]=[C:24]([C:2]2[CH:18]=[CH:17][CH:16]=[CH:15][C:3]=2[O:4][C:5]2[CH:10]=[CH:9][N:8]=[C:7]([C:11]([F:14])([F:13])[F:12])[CH:6]=2)[CH:23]=[CH:22][C:21]=1[C:35]1[CH:40]=[N:39][C:38]([NH2:41])=[N:37][CH:36]=1
Reactant: CC1(C)OB(c2ccc(-c3cnc(N)nc3)c(F)c2)OC1(C)C
Reactant: FC(F)(F)c1cc(Oc2ccccc2Br)ccn1
Product: Nc1ncc(-c2ccc(-c3ccccc3Oc3ccnc(C(F)(F)F)c3)cc2F)cn1

Procedure:
The title compound was prepared in a manner similar to that described in Example 88 using 4-(2-bromophenoxy)-2-(trifluoromethyl)pyridine and 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrimidin-2-amine. MS (ESI): mass calcd. for C22H14F4N4O, 426.11; m/z found, 426.9 [M+H]+. 1H NMR (400 MHz, DMSO-d6) 58.51 (d, J=5.7, 1H), 8.38 (d, J=1.5, 2H), 7.62 (dd, J=7.6, 1.8, 1H), 7.56-7.42 (m, 3H), 7.38-7.30 (m, 4H), 7.04 (dd, J=5.6, 2.4, 1H), 6.84 (s, 2H).
Reaction SMILES: [C:1]1(=[O:9])[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH2:10]([Mg]Br)[CH3:11].C(=O)(O)[O-].[Na+]>O1CCCC1>[CH2:10]([C:1]1([OH:9])[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1)[CH3:11]
Reactant: CC[Mg]Br
Reactant: O=C1CCCCCCC1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: C1CCOC1
Product: CCC1(O)CCCCCCC1
Reaction time: 8 h
Yield: 31.6 %

Procedure:
To a 1000-mL 3-necked round bottom flask equipped with a 500-mL pressure equalizing addition funnel, a nitrogen inlet with thermocouple and an overhead stirrer was added 100 g (0.79 mol) of cyclooctanone dissolved in 250 mL of dry tetrahydrofuran. The addition funnel was charged with 290 mL (0.869 mol, 10% excess) of ethyl magnesium bromide (2.0M solution in ether) which was then added to the cooled ketone over 2 hours. Stirring was continued at room temperature overnight followed by 8 hours at reflux. Excess Grignard reagent was discharged by the cautious addition of 100 mL of saturated sodium bicarbonate solution. The resulting suspension was filtered through a bed of Celite, the filtrate diluted with 500 mL of ether and the combined organics washed several times with saturated sodium bicarbonate, once with brine and then dried for 1 hr over anhydrous magnesium sulfate. Filtration and removal of the solvent at reduced pressure resulted in a light-colored oil which was distilled twice from Na2CO3 through a base-washed 15 cm Vigreux (bp 65° C.@1 mmHg) to yield 39 g (32%) of the title alcohol as a clear, colorless oil.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][C:10]([N:12]([C@@H:20]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH2:21][N:22]2[CH2:26][CH2:25][CH2:24][CH2:23]2)[CH2:13][CH2:14][C:15]([O:17]CC)=O)=[O:11])[CH:5]=[CH:6][C:7]=1[Cl:8].[H-].[Na+]>>[Cl:1][C:2]1[CH:3]=[C:4]([CH:9]2[C:15](=[O:17])[CH2:14][CH2:13][N:12]([C@@H:20]([C:27]3[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=3)[CH2:21][N:22]3[CH2:26][CH2:25][CH2:24][CH2:23]3)[C:10]2=[O:11])[CH:5]=[CH:6][C:7]=1[Cl:8]
Reactant: CCOC(=O)CCN(C(=O)Cc1ccc(Cl)c(Cl)c1)[C@H](CN1CCCC1)c1ccccc1
Agent: [H-]
Agent: [Na+]
Product: O=C1CCN([C@H](CN2CCCC2)c2ccccc2)C(=O)C1c1ccc(Cl)c(Cl)c1
Yield: 95.7 %

Procedure:
The operation is carried out as in Example 2 starting with 28.6 g of the product obtained in Example 11, using 3.3 g sodium hydride. 24.74 g of desired product is obtained which is used as it is for the following example. M.p.=110°-115° C. crystallized from diethyl ether.
Reaction SMILES: [C:1](=[O:16])([O:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)OC1C=CC=CC=1>O>[C:1]([O:9][C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1)(=[O:16])[C:1]([O:9][C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1)=[O:16]
Reactant: O=C(Oc1ccccc1)Oc1ccccc1
Solvent: O
Product: O=C(Oc1ccccc1)C(=O)Oc1ccccc1

Procedure:
400 parts of distilled water were added to 200 parts of diphenyl carbonate, obtained through the decarbonylation reaction of diphenyl oxalate using triphenyl phosphine and aluminum chloride as catalysts, the mixture was heated to 90° C. and stirred for 1 hour. This washing step was repeated twice to obtain diphenyl carbonate containing 7.9 ppm of hydrolyzable chlorine. An ester interchange reaction between this diphenyl carbonate and bisphenol A was carried out in the same manner as in Example 1 except that a disodium salt of bisphenol A was used in place of sodium hydroxide as an ester interchange catalyst in an amount of 2.0×10−6 mole, in terms of sodium, based on bisphenol A, to synthesize polycarbonate. A pellet of this polycarbonate was used for the measurement of its physical properties. The conditions and results are shown in Tables III-A and III-B below.
Reaction SMILES: I[C:2]1[CH:12]=[CH:11][C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])=[CH:4][CH:3]=1.[F:13][C:14]1[CH:19]=[C:18]([F:20])[CH:17]=[CH:16][C:15]=1B(O)O.C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.C(O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:13][C:14]1[CH:19]=[C:18]([F:20])[CH:17]=[CH:16][C:15]=1[C:2]1[CH:12]=[CH:11][C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])=[CH:4][CH:3]=1
Reactant: OB(O)c1ccc(F)cc1F
Reactant: CCOC(=O)c1ccc(I)cc1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: CCO
Product: CCOC(=O)c1ccc(-c2ccc(F)cc2F)cc1
Temperature: 25 °C
Reaction time: 0.17 h

Procedure:
0.009 g of Pd(PPh3)4 was added to a solution of 0.091 g of ethyl 4-iodobenzoate in 0.96 ml of degassed toluene and stirred at room temperature for 10 minutes. Then a solution of 0.047 g of 2,4-difluorophenylboronic acid in 0.114 ml of ethanol and 0.201 ml of a 2N Na2CO3 solution was added to the reaction solution. The solution was heated at 100° C. overnight. The reaction mixture was then concentrated in vacuo, and water/ethyl acetate were added to the residue. The aqueous phase was extracted three times with ethyl acetate and dried over sodium sulfate, and the solvent was removed in vacuo and purified by preparative HPLC.
Reaction SMILES: [CH3:1][C:2]([C:6]1[CH:11]=[CH:10][N:9]=[CH:8][CH:7]=1)([CH3:5])[CH2:3][OH:4].[H][H].[C:14]([OH:17])(=[O:16])[CH3:15]>[Pt]=O>[C:14]([OH:17])(=[O:16])[CH3:15].[CH3:5][C:2]([CH:6]1[CH2:7][CH2:8][NH:9][CH2:10][CH2:11]1)([CH3:1])[CH2:3][OH:4]
Reactant: CC(C)(CO)c1ccncc1
Reactant: [H][H]
Agent: O=[Pt]
Solvent: CC(=O)O
Product: CC(C)(CO)C1CCNCC1

Procedure:
4-(1,1-Dimethyl-2-hydroxyethyl)pyridine [which may be prepared as described by Fraenkel et al, J. Amer. Chem. Soc. (1971), 93, 7228; 3 g] was dissolved in acetic acid (30 ml) and hydrogenated in the presence of platinum oxide catalyst for 10 hours at a maximum temperature of 37° C. and a pressure of 50 pounds per square inch, until 100% of the theoretical uptake of hydrogen had occurred. The reaction mixture was then filtered and the filtrate was evaporated under reduced pressure (15 mmHg) to give a pale yellow oil, which was then distilled (b.p. 120° C./0.2 mmHg) to give a colourless oil, which was recrystallised from a mixture of ethanol and diethyl ether to give 4-(1,1-dimethyl-2-hydroxyethyl)piperidine acetate (1.8 g), m.p. 108°-110° C., in the form of colourless crystals.
Reaction SMILES: C([O:4][C:5]1[CH:6]=[C:7]([CH:11]=[C:12]([N+:18]([O-:20])=[O:19])[C:13]=1[O:14]C(=O)C)[C:8]([OH:10])=O)(=O)C.[NH2:21][CH2:22][CH2:23][CH2:24][OH:25]>>[OH:25][CH2:24][CH2:23][CH2:22][NH:21][C:8](=[O:10])[C:7]1[CH:11]=[C:12]([N+:18]([O-:20])=[O:19])[C:13]([OH:14])=[C:5]([OH:4])[CH:6]=1
Reactant: CC(=O)Oc1cc(C(=O)O)cc([N+](=O)[O-])c1OC(C)=O
Reactant: NCCCO
Product: O=C(NCCCO)c1cc(O)c(O)c([N+](=O)[O-])c1
Yield: 85 %

Procedure:
The procedures described in Examples 43 and 44 were repeated using 3,4-diacetoxy-5-nitrobenzoic acid and 3-aminopropan-1-ol. Yield 85%, m.p. 160°-163° C.
Reaction SMILES: [OH:1][C@@H:2]([CH3:19])[C:3]([NH:5][C@@H:6]1[C:12](=[O:13])[NH:11][C:10]2[CH:14]=[CH:15][CH:16]=[CH:17][C:9]=2[O:8][C@@H:7]1[CH3:18])=[O:4].N1C=CC=CC=1.Cl[C:27]([O:29][C:30]1[CH:35]=[CH:34][C:33]([N+:36]([O-:38])=[O:37])=[CH:32][CH:31]=1)=[O:28]>ClCCl>[N+:36]([C:33]1[CH:32]=[CH:31][C:30]([O:29][C:27](=[O:28])[O:1][C@H:2]([C:3](=[O:4])[NH:5][C@@H:6]2[C:12](=[O:13])[NH:11][C:10]3[CH:14]=[CH:15][CH:16]=[CH:17][C:9]=3[O:8][C@@H:7]2[CH3:18])[CH3:19])=[CH:35][CH:34]=1)([O-:38])=[O:37]
Reactant: C[C@H](O)C(=O)N[C@@H]1C(=O)Nc2ccccc2O[C@@H]1C
Reactant: O=C(Cl)Oc1ccc([N+](=O)[O-])cc1
Solvent: c1ccncc1
Solvent: ClCCl
Product: C[C@H](OC(=O)Oc1ccc([N+](=O)[O-])cc1)C(=O)N[C@@H]1C(=O)Nc2ccccc2O[C@@H]1C
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A mixture of 290 mg (1.1 mmol) of (S)-2-hydroxy-N-((6R,7S)-6-methyl-8-oxo-6,7,8,9-tetrahydro-5-oxa-9-aza-benzocyclohepten-7-yl)-propionamide and 0.177 ml (2.19 mmol) of pyridine in 10 ml of dichloromethane was treated with 274 mg (1.32 mmol) of 4-nitrophenyl chloroformate and stirred overnight at room temperature. The solvent was removed by distillation and the crude product was purified by flash-chromatography on silica gel using an ascending gradient of ethyl acetate in heptane as the eluent to yield 220 mg (47% of theory) of the title compound as a white solid, MS m/e (%): 430.3 (M+H+, 100).
Reaction SMILES: C(=[N:4][N:5]=[C:6]1[NH:10][C:9](=[O:11])[CH2:8][N:7]1[CH2:12][C:13]([O:15]C)=O)(C)C.[OH-].[Na+].Cl>CO>[N:7]12[CH2:8][C:9](=[O:11])[NH:10][C:6]1=[N:5][NH:4][C:13](=[O:15])[CH2:12]2
Reactant: COC(=O)CN1CC(=O)NC1=NN=C(C)C
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: O=C1CN2CC(=O)NC2=NN1
Temperature: 25 °C
Reaction time: 16 h
Yield: 48.7 %

Procedure:
To 226 mg of 2-isopropylidenehydrazono-1-methoxycarbonylmethylimidazolidin-4-one were added 10 ml of methanol and 1 ml of a 2N sodium hydroxide solution, and the mixture was stirred for 16 hours at room temperature. The reaction mixture obtained was neutralized with the addition of 1N hydrochloric acid, concentrated under reduced pressure, and the residue formed was recrystallized from methanol to obtain 75 mg of 1,4,5,7-tetraazabicyclo[4,3,0]nonan-5-ene-3,8-dione.
Reaction SMILES: Br[C@@H:2]1[CH2:7][C@H:6]2[C@H:8]3[C@H:18]([CH2:19][CH2:20][C@:4]2([CH3:5])[C:3]1=[O:21])[C@:16]1([CH3:17])[C:11]([CH2:12][CH2:13][CH2:14][CH2:15]1)=[CH:10][CH2:9]3.[O:22]=O.[OH-].[Na+].Cl>N1C=CC=CC=1.O>[OH:22][C@@H:2]1[CH2:7][C@H:6]2[C@H:8]3[C@H:18]([CH2:19][CH2:20][C@:4]2([CH3:5])[C:3]1=[O:21])[C@:16]1([CH3:17])[C:11]([CH2:12][CH2:13][CH2:14][CH2:15]1)=[CH:10][CH2:9]3
Reactant: O=O
Reactant: C[C@]12CCCCC1=CC[C@@H]1[C@@H]2CC[C@]2(C)C(=O)[C@H](Br)C[C@@H]12
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: c1ccncc1
Product: C[C@]12CCCCC1=CC[C@@H]1[C@@H]2CC[C@]2(C)C(=O)[C@H](O)C[C@@H]12
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
To a solution of 16α-Bromo-5-androsten-17-one (7.92 g, 20 mmoles) in pyridine (300 ml) and water (64 ml) in an oxygen atmosphere was added 36 ml (36 mmoles) of 1N NaOH. After stirring the mixture for 15 minutes at room temperature under O2, it was added to 1 L of ice water containing 330 ml of concentrated HCl. The crystallized precipitate which formed was filtered off, washed with water, and recrystallized from methanol as leaflets (2, 80 g), mp 168°-172°. HPLC of the mother liquor on a silica gel column using isopropyl alcohol n-hexane as eluent furnished an additional 1.4 g of light yellow prisms, mp 170°-174°. The total yield of 16α-ol was 3.94 g (68.4%).
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][C:4](=[N:7][O:8][CH:9]2[CH2:14][CH2:13][N:12]([C:15]([O:17][CH:18]([CH3:20])[CH3:19])=[O:16])[CH2:11][CH2:10]2)[CH2:3][CH2:2]1.Cl[C:22]1[C:23]([F:32])=[CH:24][C:25]([N+:29]([O-:31])=[O:30])=[C:26]([NH2:28])[CH:27]=1.C(N(C(C)C)CC)(C)C>CS(C)=O.C([O-])(O)=O.[Na+]>[CH:18]([O:17][C:15]([N:12]1[CH2:11][CH2:10][CH:9]([O:8][N:7]=[C:4]2[CH2:3][CH2:2][N:1]([C:22]3[CH:27]=[C:26]([NH2:28])[C:25]([N+:29]([O-:31])=[O:30])=[CH:24][C:23]=3[F:32])[CH2:6][CH2:5]2)[CH2:14][CH2:13]1)=[O:16])([CH3:20])[CH3:19]
Reactant: Nc1cc(Cl)c(F)cc1[N+](=O)[O-]
Reactant: CC(C)OC(=O)N1CCC(ON=C2CCNCC2)CC1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CS(C)=O
Solvent: CCN(C(C)C)C(C)C
Product: CC(C)OC(=O)N1CCC(ON=C2CCN(c3cc(N)c([N+](=O)[O-])cc3F)CC2)CC1
Temperature: 110 °C
Reaction time: 72 h

Procedure:
2d (0.12 g), 5-chloro-4-fluoro-2-nitro-phenylamine (0.1 g) and diisopropylethylamine (0.1 mL) were combined in 1.2 mL of DMSO and stirred at 110° C. for 3 days. The mixture was cooled to room temperature, diluted with aqueous NaHCO3 (5 mL) and extracted with EtOAc (5 mL). The organic layer was concentrated under vacuum and purified on column chromatography (eluent: 10 to 50% EtOAc in hexane+0.1% triethylamine) to yield 60a.