Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][C:3]=1[C:11]([C:14]#[N:15])([CH3:13])[CH3:12].CN(C)C=O.[NH2:21][C:22]1[CH:23]=[C:24]([CH:39]=[CH:40][C:41]=1[F:42])[O:25][C:26]1[N:31]=[C:30]2[S:32][C:33]([NH:35][C:36](=[O:38])[CH3:37])=[N:34][C:29]2=[CH:28][CH:27]=1.O>C(Cl)(=O)C(Cl)=O.CN(C)C(=O)C>[C:36]([NH:35][C:33]1[S:32][C:30]2[C:29]([N:34]=1)=[CH:28][CH:27]=[C:26]([O:25][C:24]1[CH:39]=[CH:40][C:41]([F:42])=[C:22]([NH:21][C:6](=[O:8])[C:5]3[CH:9]=[CH:10][C:2]([Cl:1])=[C:3]([C:11]([C:14]#[N:15])([CH3:13])[CH3:12])[CH:4]=3)[CH:23]=1)[N:31]=2)(=[O:38])[CH3:37]
Reactant: CC(C)(C#N)c1cc(C(=O)O)ccc1Cl
Reactant: CC(=O)Nc1nc2ccc(Oc3ccc(F)c(N)c3)nc2s1
Agent: O=C(Cl)C(=O)Cl
Solvent: O
Solvent: CC(=O)N(C)C
Solvent: CN(C)C=O
Product: CC(=O)Nc1nc2ccc(Oc3ccc(F)c(NC(=O)c4ccc(Cl)c(C(C)(C)C#N)c4)c3)nc2s1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 21.4 %

Procedure:
To a solution of 4-chloro-3-(1-cyano-1-methylethyl)benzoic acid (0.11 g, 0.5 mmol) in oxalyl chloride (0.5 mL) was added N,N-dimethylformamide (40 μL), and the mixture was stirred at room temperature for 30 min, and concentrated to dryness under reduced pressure. This was dissolved in a mixture of N,N-dimethylacetamide (1 mL) and tetrahydrofuran (1 mL), and a solution was added dropwise to a solution of N-[5-(3-amino-4-fluorophenoxy)[1,3]thiazolo[5,4-b]pyridin-2-yl]acetamide (0.11 g, 0.33 mmol) produced in Example C64(ii) in N,N-dimethylacetamide (1 mL) under ice-cooling. The reaction mixture was stirred at room temperature for 3 hr, and poured into water (100 mL), and the mixture was extracted with ethyl acetate (100 mL×2). The ethyl acetate layers were combined, and dried over anhydrous sodium sulfate. The insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (ethyl acetate/hexane=0/100→100/0), and recrystallized from methanol to give the title compound (37 mg, 21%) as colorless crystals.
Reaction SMILES: C(NC(C)C)(C)C.C([Li])CCC.[F:13][CH:14]([P:16](=[O:21])([O:19][CH3:20])[O:17][CH3:18])[F:15].[CH3:22][C:23]([CH3:37])=[CH:24][CH2:25][CH2:26]/[C:27](/[CH3:36])=[CH:28]/[CH2:29][CH2:30]/[C:31](/[CH3:35])=[CH:32]/[CH:33]=[O:34].Cl>O1CCCC1>[F:13][C:14]([P:16](=[O:21])([O:19][CH3:20])[O:17][CH3:18])([F:15])[CH:33]([OH:34])[CH:32]=[C:31]([CH3:35])[CH2:30][CH2:29][CH:28]=[C:27]([CH3:36])[CH2:26][CH2:25][CH:24]=[C:23]([CH3:22])[CH3:37]
Reactant: COP(=O)(OC)C(F)F
Reactant: CC(C)=CCC/C(C)=C/CC/C(C)=C/C=O
Agent: Cl
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CC(C)NC(C)C
Product: COP(=O)(OC)C(F)(F)C(O)C=C(C)CCC=C(C)CCC=C(C)C
Temperature: -78 °C
Reaction time: 0.5 h
Yield: 39 %

Procedure:
Combine diisopropylamine (22.24 mL, 0.159 mol) with tetrahydrofuran (250 mL) and cool to -20° C. Add n-butyllithium (63.3 mL, 2.5N in hexane, 0.159 mol) dropwise to the solution. Stir for 30 minutes and cool to -78° C. Add dropwise a solution of dimethyl difluoromethylphosphonate (25.8 g, 0.159 mol) in tetrahydrofuran (20 mL) while maintaining the temperature below -75° C. After addition is complete, stir for 2 minutes and then slowly add a solution of trans, trans-farnesal [prepared according to Biller, S. A; Forster, C. Tetrahedron 1990, 46(19), 6645](14 g, 0.0636 mol) prepared in step a above, in tetrahydrofuran (10 mL) maintaining the temperature below -72° C. After addition is complete, stir for an additional 2 hours at -78° C. and then pour the reaction into 0.1N hydrochloric acid (500 mL). Extract the reaction with diethyl ether (2×1L). Combine the organic phases, dry over anhydrous magnesium sulfate, filter and concentrate under vacuum. Purify the residue by flash chromatography [40% ethyl acetate/hexane, Rf (50% ethyl acetate/hexane)=0.44] to provide the title compound (9.3 g, 39%) as an oil.
Reaction SMILES: [C:1]([NH:8][NH2:9])([O:3][C:4](C)(C)[CH3:5])=[O:2].CCN(C(C)C)C(C)C.C(Cl)(OCC1[C:35]2[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=2)[C:29]2[C:24]1=[CH:25][CH:26]=[CH:27][CH:28]=2)=O>C(Cl)Cl>[CH:34]1[C:35]2[CH:5]([CH2:4][O:3][C:1]([NH:8][NH2:9])=[O:2])[C:24]3[C:29](=[CH:28][CH:27]=[CH:26][CH:25]=3)[C:30]=2[CH:31]=[CH:32][CH:33]=1
Reactant: O=C(Cl)OCC1c2ccccc2-c2ccccc21
Reactant: CC(C)(C)OC(=O)NN
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: NNC(=O)OCC1c2ccccc2-c2ccccc21
Temperature: 0 °C
Reaction time: 8 h
Yield: 93.7 %

Procedure:
Boc-hydrazine (10.0 g, 75.6 mmol) and DIPEA (12.95 ml, 75.6 mmol) were dissolved in dry CH2Cl2 (200 ml) and cooled to 0° C. FmocCl (19.6 g, 75.8 mmol), dissolved in dry CH2Cl2 (100 ml), was then added over the course of 30 minutes, and the mixture was stirred overnight at room temperature. The organic phase was extracted with water (200 ml) and evaporated to a volume of about 100 ml. Trifluoroacetic acid (100 ml) was then carefully added at 0° C., and the mixture was stirred for 1.5 hours. The product was precipitated by careful addition of saturated Na2CO3 solution (300 ml) and dried, giving a colourless solid (18.02 g, 70.8 mmol, 94%).
Reaction SMILES: [OH-].[K+].[C:3]1([C:9]2[N:10]=[C:11]([CH2:14][O:15]C(=O)C3C=CC=CC=3)[S:12][CH:13]=2)[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.C(O)(=O)C1C=CC=CC=1>CCO>[C:3]1([C:9]2[N:10]=[C:11]([CH2:14][OH:15])[S:12][CH:13]=2)[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1
Reactant: O=C(OCc1nc(-c2ccccc2)cs1)c1ccccc1
Agent: O=C(O)c1ccccc1
Agent: [K+]
Agent: [OH-]
Solvent: CCO
Product: OCc1nc(-c2ccccc2)cs1
Temperature: 25 °C
Reaction time: 1 h
Yield: 87.4 %

Procedure:
Potassium hydroxide (1.06 g, 18.84 mmol) was added to an ice cooled solution of benzoic acid (4-phenylthiazol-2-yl)methyl benzoate (3.71 g, 12.56 mmol) in EtOH (40 mL). The reaction mixture was slowly warmed to room temperature and allowed to stir for 1 h. The reaction mixture was concentrated under reduced pressure and then diluted with water. The organic product was extracted with EtOAc, washed with brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The crude product was purified by column chromatography (silica 60-120 mesh, eluant 10% EtOAc in petroleum ether) to get the pure (4-phenylthiazol-2-yl)methanol (2.1 g, yield 87%). 1H NMR (400 MHz, CDCl3) δ 7.89-7.87 (m, 2H), 7.46-7.41 (m, 3H), 7.37-7.33 (m, 1H), 5.01 (s, 2H). MS (ESI) m/z: Calculated for C10H9NOS: 191.04. found: 192.2 (M+H)+.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6](Cl)[C:5]([CH3:9])=[CH:4][N:3]=1.[N:10]1([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]1.CCN(C(C)C)C(C)C>CN(C=O)C.O>[Cl:1][C:2]1[N:7]=[C:6]([N:13]2[CH2:12][CH2:11][N:10]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:15][CH2:14]2)[C:5]([CH3:9])=[CH:4][N:3]=1
Reactant: Cc1cnc(Cl)nc1Cl
Reactant: CC(C)(C)OC(=O)N1CCNCC1
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Solvent: O
Product: Cc1cnc(Cl)nc1N1CCN(C(=O)OC(C)(C)C)CC1
Temperature: 25 °C
Reaction time: 8 h
Yield: 96.3 %

Procedure:
To a solution of 2,4-dichloro-5-methylpyrimidine (0.75 g, 4.6 mmol) in dry DMF (15.5 mL) was added tert-butyl piperazine-1-carboxylate (0.9 g, 4.85 mmol) followed by DIEA (0.91 mL, 5.5 mmol) at 0° C., and the mixture was stirred to room temperature overnight. LCMS showed the reaction was completed. The reaction was diluted with water (120 mL), and the solid was filtered. The residue was washed with water and dried to give the title compound (1.386 g, 96%) as a white solid. MS (ES+) C14H21ClN4O2 requires: 312. found: 313 [M+H]+
Reaction SMILES: [CH3:1][C:2](=O)[CH:3]([S:7][C:8]1[N:12]=[CH:11][NH:10][N:9]=1)[C:4](=O)[CH3:5].[C:14]1([NH:20][NH2:21])[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1>C(O)C>[CH3:1][C:2]1[C:3]([S:7][C:8]2[N:12]=[CH:11][NH:10][N:9]=2)=[C:4]([CH3:5])[N:20]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[N:21]=1
Reactant: NNc1ccccc1
Reactant: CC(=O)C(Sc1nc[nH]n1)C(C)=O
Solvent: CCO
Product: Cc1nn(-c2ccccc2)c(C)c1Sc1nc[nH]n1
Temperature: 100 °C
Reaction time: 4 h

Procedure:
A mixture of 3-(2,4-pentanedion-3-yl)thio-1H-1,2,4-triazole (Example 46-a) (2 g), phenylhydrazine (1 ml) and ethanol (10 ml) was heated and stirred for 4 hours on an oil bath at 100° C. The reaction solution was concentrated under reduced pressure, and then the residue was crystallized from ethanol-ethyl acetate to yield the title compound (1.42 g).
Reaction SMILES: [CH3:1][CH2:2][CH2:3][CH2:4][CH2:5][CH:6]([OH:12])[CH2:7][CH2:8][CH2:9][CH2:10][CH3:11].[CH3:13][S:14](Cl)(=[O:16])=[O:15].Cl>N1C=CC=CC=1>[CH3:13][S:14]([O:12][CH:6]([CH2:5][CH2:4][CH2:3][CH2:2][CH3:1])[CH2:7][CH2:8][CH2:9][CH2:10][CH3:11])(=[O:16])=[O:15]
Reactant: CCCCCC(O)CCCCC
Reactant: CS(=O)(=O)Cl
Agent: Cl
Solvent: c1ccncc1
Product: CCCCCC(CCCCC)OS(C)(=O)=O
Reaction time: 8 h
Yield: 105 %

Procedure:
After dissolving 29.95 g (0.17 mol) of 6-undecanol to 60 mL of pyridine, 29.98 g (0.26 mol) of methanesulfonyl chloride was added dropwise under cooling with ice and the mixture was stirred overnight. Thereafter, 35 mL of 0.5 N aqueous hydrochloric acid was added and the mixture was extracted twice with 200 mL of ethyl acetate. The organic layer was washed with 100 mL of water and a saturated aqueous solution of sodium chloride in that order and thereafter dried over anhydrous magnesium sulfate. After filtering off the magnesium sulfate, the solvent was distilled off to give 44.7 g of 6-methanesulfonyloxy-undecane.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][N:11]=[CH:10][CH:9]=2)[CH:5]=[CH:4][C:3]=1[NH:14][S:15]([C:18]1[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][CH:19]=1)(=[O:17])=[O:16].[Br:25][C:26]1[CH:27]=[CH:28][C:29]([O:36][CH3:37])=[C:30]([S:32](Cl)(=[O:34])=[O:33])[CH:31]=1>N1C=CC=CC=1.C(OCC)(=O)C>[Br:25][C:26]1[CH:27]=[CH:28][C:29]([O:36][CH3:37])=[C:30]([S:32]([NH:1][C:2]2[CH:7]=[C:6]([C:8]3[CH:9]=[CH:10][N:11]=[CH:12][CH:13]=3)[CH:5]=[CH:4][C:3]=2[NH:14][S:15]([C:18]2[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][CH:19]=2)(=[O:16])=[O:17])(=[O:33])=[O:34])[CH:31]=1
Reactant: Nc1cc(-c2ccncc2)ccc1NS(=O)(=O)c1ccc(Cl)cc1
Reactant: COc1ccc(Br)cc1S(=O)(=O)Cl
Solvent: CCOC(C)=O
Solvent: c1ccncc1
Product: COc1ccc(Br)cc1S(=O)(=O)Nc1cc(-c2ccncc2)ccc1NS(=O)(=O)c1ccc(Cl)cc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 80.5 %

Procedure:
To a solution of N-(2-amino-4-pyridin-4-ylphenyl)-4-chlorobenzene sulfonamide (0.1 mmol) in pyridine (0.5 mL), 5-bromo-2-methoxy-benzenesulfonyl chloride (0.12 mmol) was added. The reaction mixture was stirred at room temperature for 2 h and then was diluted with ethyl acetate (10 mL). The contents were washed with brine (10 mL), dried over sodium sulfate, and concentrated under vacuum. The residue obtained was purified by column chromatography eluting with hexanes/ethyl acetate (1:1) followed by ethyl acetate to give 49 mg of 5-bromo-N-[2-(4-chlorobenzenesulfonylamino) -5-pyridin-4-ylphenyl]-2-methoxybenzenesulfonamide. LC: Tr 0.94 min, MS: 610.8 (M+1)+.
Reaction SMILES: [NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:12]([C:14]3[CH:21]=[C:20]([Cl:22])[C:17]([C:18]#[N:19])=[C:16]([CH:23]4[CH2:26][NH:25][CH2:24]4)[C:15]=3[O:27][CH2:28][CH3:29])[CH3:13])[N:9]=[C:10]([CH3:11])[C:3]=12.C(N(CC)CC)C.Br[CH2:38][CH2:39][OH:40].C(=O)(O)[O-].[Na+]>O1CCCC1>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:12]([C:14]3[CH:21]=[C:20]([Cl:22])[C:17]([C:18]#[N:19])=[C:16]([CH:23]4[CH2:24][N:25]([CH2:38][CH2:39][OH:40])[CH2:26]4)[C:15]=3[O:27][CH2:28][CH3:29])[CH3:13])[N:9]=[C:10]([CH3:11])[C:3]=12
Reactant: OCCBr
Reactant: CCOc1c(C(C)n2nc(C)c3c(N)ncnc32)cc(Cl)c(C#N)c1C1CNC1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: CCOc1c(C(C)n2nc(C)c3c(N)ncnc32)cc(Cl)c(C#N)c1C1CN(CCO)C1
Temperature: 60 °C
Reaction time: 6 h
Yield: 44.5 %

Procedure:
A solution of 4-[1-(4-amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-2-azetidin-3-yl-6-chloro-3-ethoxybenzonitrile (300 mg, 0.74 mmol, chiral intermediate from Example 212) in tetrahydrofuran (14 mL) was treated with triethylamine (260 μL, 1.8 mmol) followed by 2-bromoethanol (63 μL, 0.89 mmol) dropwise and stirred at 60° C. for 6 h. The reaction mixture was treated with additional 2-bromoethanol (26 μL, 0.37 mmol) and stirred at 60° C. for another 6 h. The reaction mixture was poured into saturated sodium bicarbonate solution and extracted with ethyl acetate. The organic layer was concentrated and purified by preparative LCMS (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 60 mL/min) to give the desired product (0.15 g, 44%). The product was isolated as a single enantiomer. 1H NMR (400 MHz, DMSO-d6) δ 8.19 (s, 1H), 7.56 (s, 1H), 6.36-6.25 (m, 1H), 4.48 (br s, 1H), 4.19-4.07 (m, 1H), 4.04-3.94 (m, 2H), 3.91-3.82 (m, 1H), 3.81-3.72 (m, 1H), 3.20-3.08 (m, 2H), 2.62 (s, 2H), 2.57 (s, 3H), 1.79 (d, J=6.8 Hz, 3H), 1.40 (t, J=6.6 Hz, 3H). LCMS for C22H27ClN7O2 (M+H)+: m/z=456.2; Found: 456.1.
Reaction SMILES: [NH2:1][C:2]1[C:3]2[C:25]([CH3:31])([C:26](OCC)=[O:27])[C:24](=[O:32])[NH:23][C:4]=2[N:5]=[C:6]([C:8]2[C:16]3[C:11](=[N:12][CH:13]=[CH:14][CH:15]=3)[N:10]([CH2:17][CH2:18][C:19]([F:22])([F:21])[F:20])[N:9]=2)[N:7]=1.[CH:33]1([NH2:36])[CH2:35][CH2:34]1>>[NH2:1][C:2]1[C:3]2[C:25]([CH3:31])([C:26]([NH:36][CH:33]3[CH2:35][CH2:34]3)=[O:27])[C:24](=[O:32])[NH:23][C:4]=2[N:5]=[C:6]([C:8]2[C:16]3[C:11](=[N:12][CH:13]=[CH:14][CH:15]=3)[N:10]([CH2:17][CH2:18][C:19]([F:20])([F:22])[F:21])[N:9]=2)[N:7]=1
Reactant: CCOC(=O)C1(C)C(=O)Nc2nc(-c3nn(CCC(F)(F)F)c4ncccc34)nc(N)c21
Reactant: NC1CC1
Product: CC1(C(=O)NC2CC2)C(=O)Nc2nc(-c3nn(CCC(F)(F)F)c4ncccc34)nc(N)c21

Procedure:
To the intermediate from Step A above (165 mg, 0.367 mmol) was added cyclopropylamine (3.31 mL, 47.7 mmol) and the resultant mixture heated to 50° C. for 16 hours. The reaction mixture was concentrated in vacuo and the residue purified by silica gel column chromatography using a DCM/MeOH (with 0.5% NH4OH) gradient. Chiral separation using SFC on a Chiralcel OJ-H column provided both enantiomers of the title compound. 1H NMR (500 MHz, DMSO-d6): δ 11.23 (1H, s), 9.02 (1H, dd, J=8.08, 1.55 Hz), 8.62 (1H, dd, J=4.50, 1.57 Hz), 7.64 (1H, d, J=4.05 Hz), 7.37 (1H, dd, J=8.08, 4.49 Hz), 6.76 (2H, s), 4.81 (2H, t, J=6.60 Hz), 3.06-2.94 (2H, m), 2.67-2.60 (1H, m), 1.55 (3H, s), 0.62-0.53 (2H, m), 0.50-0.41 (2H, m). m/z=461.3 (M+H).
Reaction SMILES: [CH2:1]([O:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[O:10][CH2:11][CH3:12])[CH3:2].[C:13]1(=[O:23])[O:18][C:16](=[O:17])[C@H:15]2[CH2:19][CH2:20][CH2:21][CH2:22][C@@H:14]12>>[CH2:11]([O:10][C:5]1[CH:6]=[C:7]([CH:8]=[CH:9][C:4]=1[O:3][CH2:1][CH3:2])[C:13]([C@H:14]1[CH2:22][CH2:21][CH2:20][CH2:19][C@H:15]1[C:16]([OH:18])=[O:17])=[O:23])[CH3:12]
Reactant: O=C1OC(=O)[C@@H]2CCCC[C@H]12
Reactant: CCOc1ccccc1OCC
Product: CCOc1ccc(C(=O)[C@H]2CCCC[C@H]2C(=O)O)cc1OCC

Procedure:
Prepared from 1,2-diethoxybenzene and cis-hexahydrophthalic anhydride as described for compound A. M.p.: low melting solid.
Reaction SMILES: C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[O:20]1[CH2:25][CH2:24][N:23]([CH2:26][CH2:27][OH:28])[CH2:22][CH2:21]1.CCOC(/N=N/C(OCC)=O)=O.O1CCCCC1[N:47]1[C:55]2[C:50](=[CH:51][C:52]([C:56]3[N:60]=[CH:59][N:58](C(C4C=CC=CC=4)(C4C=CC=CC=4)C4C=CC=CC=4)[N:57]=3)=[CH:53][CH:54]=2)[C:49]([C:80]2[CH:81]=[C:82](O)[CH:83]=[CH:84][CH:85]=2)=[N:48]1.Cl>O1CCCC1>[NH:57]1[C:56]([C:52]2[CH:51]=[C:50]3[C:55](=[CH:54][CH:53]=2)[NH:47][N:48]=[C:49]3[C:80]2[CH:81]=[CH:82][CH:83]=[C:84]([O:28][CH2:27][CH2:26][N:23]3[CH2:24][CH2:25][O:20][CH2:21][CH2:22]3)[CH:85]=2)=[N:60][CH:59]=[N:58]1
Reactant: OCCN1CCOCC1
Reactant: Oc1cccc(-c2nn(C3CCCCO3)c3ccc(-c4ncn(C(c5ccccc5)(c5ccccc5)c5ccccc5)n4)cc23)c1
Agent: CCOC(=O)/N=N/C(=O)OCC
Agent: Cl
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: c1cc(OCCN2CCOCC2)cc(-c2n[nH]c3ccc(-c4ncn[nH]4)cc23)c1
Temperature: 25 °C
Reaction time: 23 h
Yield: 29.9 %

Procedure:
Triphenylphosphine (0.694 g, 2.65 mmol), tetrahydrofuran (2.12 mL), 2-morpholinoethanol (0.321 mL, 2.65 mmol) and diethylazodicarboxylate (0.418 mL, 2.65 mmol) were added to 3-{1-perhydro-2H-pyran-2-yl-5-[1-(triphenylmethyl)(1,2,4-triazol-3-yl)]-1H-indazol-3-yl}phenol (0.400 g, 0.662 mmol). The mixture was stirred at ambient temperature for 23 h and poured into aqueous 6 N hydrochloric acid (30 mL). After stirring at ambient temperature for 4 h, the mixture was extracted with ether (3×). The aqueous fraction was added to aqueous 6 N sodium hydroxide (30 mL) and the pH adjusted to 11. The solution was extracted with ethyl acetate (3×) and the organic fractions were combined and dried over anhydrous sodium sulfate, filtered and evaporated. The residue was purified by flash chromatography on silica gel pretreated with 2% triethylamine/hexanes followed by 0–20% ethyl acetate/hexanes and gave the title compound (0.0774 g, 30% yield). 1H NMR (CD3OD) δ 8.72 (m, 1H), 8.36 (br s, 1H), 8.10. (dd, 1H), 7.68 (d, 1H), 7.62 (dt, 1H), 7.56 (t, 1H), 7.46 (t, 1H), 7.04 (m, 1H), 4.28 (t, 2H), 3.72 (t, 4H), 2.89 (t, 2H), 2.65 (t, 4H). ES-MS (m/z) 391 [M+1]+.
Reaction SMILES: [C:1](=[O:4])([O-:3])O.[Na+].[C:6](=O)([O:14]C1C=CC=CC=1)[O:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1>Cl.[Cl-].C1([P+](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[C:6]([O:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)(=[O:14])[C:1]([O:3][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)=[O:4]
Reactant: O=C(Oc1ccccc1)Oc1ccccc1
Reactant: O=C([O-])O
Agent: Cl
Agent: [Cl-]
Agent: [Na+]
Product: O=C(Oc1ccccc1)C(=O)Oc1ccccc1
Yield: 80 %

Procedure:
400 parts of an aqueous solution of sodium hydrogencarbonate having a pH of 10 were added to 200 parts of diphenyl carbonate, obtained through the decarbonylation reaction of diphenyl oxalate using a hydrochloride of tetraphenyl phosphonium chloride as a catalyst, and the mixture was heated to 90° C. and stirred for 1 hour. To the obtained heavy solution (diphenyl carbonate layer) was further added 400 parts of distilled water, and the resulting mixture was heated to 90° C. and stirred for 1 hour. This additional washing step was repeated twice. The resulting heavy solution was purified by distillation in the same manner as in Example 3 at an yield of 80% to obtain diphenyl carbonate containing 0.9 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 3.0×10−5 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 II-A and II-B below.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9](=O)[CH2:10][C:11]([O:13][CH2:14][CH3:15])=[O:12])=[CH:5][CH:4]=1.C(O)C.N1C=CC=CC=1.[C:26]([C:28](=[CH:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=1[N+:39]([O-:41])=[O:40])[C:29](=[S:31])[NH2:30])#[N:27]>C(N(CC)CC)C>[C:26]([C:28]1[C:29](=[S:31])[NH:30][C:9]([C:6]2[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=2)=[C:10]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[C:32]=1[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=1[N+:39]([O-:41])=[O:40])#[N:27]
Reactant: N#CC(=Cc1ccccc1[N+](=O)[O-])C(N)=S
Reactant: CCOC(=O)CC(=O)c1ccc(OC)cc1
Solvent: CCN(CC)CC
Solvent: CCO
Solvent: c1ccncc1
Product: CCOC(=O)c1c(-c2ccc(OC)cc2)[nH]c(=S)c(C#N)c1-c1ccccc1[N+](=O)[O-]
Yield: 99.9 %

Procedure:
2.22 g (10 mmol) of ethyl 3-(4-methoxyphenyl)-3-oxopropanoate, 50 ml of ethanol, 5 ml of pyridine and 0.5 ml of triethylamine are added respectively to 2.33 g (10 mmol) of 2-cyano-3-(2-nitrophenyl)prop-2-enethioamide. The reaction mixture is stirred at reflux for 5 hours. After returning to room temperature, the solvent is evaporated and the reaction mixture is poured over crushed ice. Acetic acid is added until an acidic pH (2 to 3) is obtained. The precipitate formed is filtered, rinsed with water and diethyl ether, and then dried under vacuum to yield 4.35 g (92%) of ethyl 5-cyano-2-(4-methoxyphenyl)-4-(2-nitrophenyl)-6-thioxo-1,6-dihydropyridine-3-carboxylate in the form of a yellow powder.
Reaction SMILES: C([O:8][C:9]1[C:14](=[O:15])[CH:13]=[CH:12][N:11]([CH2:16][CH:17]([OH:20])[CH2:18][OH:19])[C:10]=1[CH:21]([OH:28])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)C1C=CC=CC=1>ClCCl.C(O)C>[OH:20][CH:17]([CH2:18][OH:19])[CH2:16][N:11]1[CH:12]=[CH:13][C:14](=[O:15])[C:9]([OH:8])=[C:10]1[CH:21]([OH:28])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1
Reactant: O=c1ccn(CC(O)CO)c(C(O)c2ccccc2)c1OCc1ccccc1
Solvent: ClCCl
Solvent: CCO
Product: O=c1ccn(CC(O)CO)c(C(O)c2ccccc2)c1O

Procedure:
3-Benzyloxy-1-(2,3-dihydroxy-propyl)-2-(hydroxy-phenyl-methyl)-1H-pyridin-4-one: From 2.1 g of 3-benzyloxy-1-(2,3-dihydroxy-propyl)-2-[phenyl-(tetrahydropyran-2-yloxy)methyl]-1H-pyridin-4-one there is obtained analogously to Example 6e, after chromatography: 3-benzyloxy-1-(2,3-dihydroxy-propyl)-2-(hydroxy-phenyl-methyl)-1H-pyridin-4-one. Colourless foam, diastereoisomeric mixture. Rf value 0.22 (silica gel 60, dichloromethane/ethanol 4/1).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:11]=[CH:10][C:6]([C:7]([NH2:9])=[O:8])=[C:5]([N+:12]([O-])=O)[CH:4]=1>CCO.[Ni]>[CH3:1][O:2][C:3]1[CH:11]=[CH:10][C:6]([C:7]([NH2:9])=[O:8])=[C:5]([NH2:12])[CH:4]=1
Reactant: COc1ccc(C(N)=O)c([N+](=O)[O-])c1
Agent: [Ni]
Solvent: CCO
Product: COc1ccc(C(N)=O)c(N)c1

Procedure:
A suspension of 4-methoxy-2-nitro-benzamide (6.9 g, 35.1 mmol) in EtOH (200 ml) was hydrogenated with Raney-Ni (4.0 g) for two days at room temperature and 50 psi. The catalyst was filtered of and washed with DMF. The solvent was evaporated under reduced pressure. Yield: 5.6 g, 95%.
Reaction SMILES: [CH2:1]([O:3][P:4](/[CH:9]=[CH:10]/[C:11]1[C:12]([O:22][CH2:23][C:24]2[CH:49]=[CH:48][C:27]([O:28][CH2:29][C:30]3[N:31]=[C:32]([C:36]4[CH:41]=[CH:40][C:39]([CH2:42][C:43]([O:45]CC)=[O:44])=[CH:38][CH:37]=4)[O:33][C:34]=3[CH3:35])=[C:26]([O:50][CH3:51])[CH:25]=2)=[N:13][N:14]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH:15]=1)([O:6][CH2:7][CH3:8])=[O:5])[CH3:2].O1CCCC1.[OH-].[Na+].Cl>O.C(O)C>[CH2:7]([O:6][P:4](/[CH:9]=[CH:10]/[C:11]1[C:12]([O:22][CH2:23][C:24]2[CH:49]=[CH:48][C:27]([O:28][CH2:29][C:30]3[N:31]=[C:32]([C:36]4[CH:41]=[CH:40][C:39]([CH2:42][C:43]([OH:45])=[O:44])=[CH:38][CH:37]=4)[O:33][C:34]=3[CH3:35])=[C:26]([O:50][CH3:51])[CH:25]=2)=[N:13][N:14]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH:15]=1)([O:3][CH2:1][CH3:2])=[O:5])[CH3:8]
Reactant: CCOC(=O)Cc1ccc(-c2nc(COc3ccc(COc4nn(-c5ccccc5)cc4/C=C/P(=O)(OCC)OCC)cc3OC)c(C)o2)cc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CCO
Solvent: O
Product: CCOP(=O)(/C=C/c1cn(-c2ccccc2)nc1OCc1ccc(OCc2nc(-c3ccc(CC(=O)O)cc3)oc2C)c(OC)c1)OCC
Temperature: 50 °C
Reaction time: 1 h
Yield: 55.8 %

Procedure:
To a mixture of ethyl {4-[4-({4-[({4-[(E)-2-(diethoxyphosphoryl)ethenyl]-1-phenyl-1H-pyrazol-3-yl)oxy)methyl]-2-methoxyphenoxy}methyl)-5-methyl-1,3-oxazol-2-yl]phenyl}acetate (0.28 g), tetrahydrofuran (2 mL) and ethanol (2 mL) was added 1N aqueous sodium hydroxide solution (1 mL), and the mixture was stirred at 50° C. for 1 hr. To the reaction mixture were added 1N hydrochloric acid (1 mL) and water, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated to give {4-[4-({4-[({4-[(E)-2-(diethoxyphosphoryl)ethenyl]-1-phenyl-1H-pyrazol-3-yl}oxy)methyl]-2-methoxyphenoxy}methyl)-5-methyl-1,3-oxazol-2-yl]phenyl}acetic acid as colorless crystals (0.15 g, yield 56%). Recrystallization from acetone-hexane gave colorless prism crystals. melting point: 119-120° C.
Reaction SMILES: [CH:1]([NH:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)([CH3:3])[CH3:2].NC1C=CC=CC=1.FC(F)(F)S([O-])(=O)=O.[Br:26][C:27]1[CH:28]=[C:29]2[C:34](=[CH:35][CH:36]=1)[NH:33][C:32](=[O:37])[C:31]([I+]C1C=CC=CC=1)=[C:30]2[OH:45]>>[Br:26][C:27]1[CH:28]=[C:29]2[C:34](=[CH:35][CH:36]=1)[NH:33][C:32](=[O:37])[C:31]([N:4]([CH:1]([CH3:3])[CH3:2])[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[C:30]2[OH:45]
Reactant: CC(C)Nc1ccccc1
Reactant: O=c1[nH]c2ccc(Br)cc2c(O)c1[I+]c1ccccc1
Agent: O=S(=O)([O-])C(F)(F)F
Solvent: Nc1ccccc1
Product: CC(C)N(c1ccccc1)c1c(O)c2cc(Br)ccc2[nH]c1=O

Procedure:
The title compound was prepared using N-isopropylaniline at 50° C. in place of aniline at room temperature according to the procedure of Intermediate 11, step c except the crude solid was purified by flash column chromatography (silica gel, 50% EtOAc-Heptane), affording the title compound.