Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [H-].[Na+].CN(C=O)C.F[C:9]1[CH:10]=[C:11]([N:19]2[CH2:23][CH2:22][N:21]([C:24]3[CH:25]=[N:26][CH:27]=[CH:28][C:29]=3[CH3:30])[C:20]2=[O:31])[CH:12]=[CH:13][C:14]=1[C:15](=[N:17][OH:18])[CH3:16].CO>C(Cl)Cl>[CH3:16][C:15]1[C:14]2[CH:13]=[CH:12][C:11]([N:19]3[CH2:23][CH2:22][N:21]([C:24]4[CH:25]=[N:26][CH:27]=[CH:28][C:29]=4[CH3:30])[C:20]3=[O:31])=[CH:10][C:9]=2[O:18][N:17]=1
Reactant: CC(=NO)c1ccc(N2CCN(c3cnccc3C)C2=O)cc1F
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: ClCCl
Solvent: CO
Product: Cc1ccncc1N1CCN(c2ccc3c(C)noc3c2)C1=O
Yield: 10.6 %

Procedure:
NaH (32.8 mg, 1.3705 mmol) and DMF (4 mL) was added to 1-[3-fluoro-4-(1-hydroxyimino-ethyl)-phenyl]-3-(4-methyl-pyridin-3-yl)-imidazolidin-2-one (111b: 150 mg, 0.4568 mmol). The resulting mixture was microwaved at 50° C. for 1 hour. The reaction was monitored by TLC (10% MeOH in DCM). The reaction mixture was partitioned between ice water and ethylacetate. The organic layer was washed with water, brine solution, dried over Na2SO4 and concentrated under reduced pressure. Purification by column chromatography on silica gel (5% MeOH in CHCl3) afforded 15 mg of the product (10.7% yield).
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][C:11]=1[CH3:12])[C:5]([O:7][CH3:8])=[O:6].[CH3:13][S:14](Cl)(=[O:16])=[O:15]>N1C=CC=CC=1>[CH3:12][C:11]1[CH:10]=[CH:9][C:4]([C:5]([O:7][CH3:8])=[O:6])=[CH:3][C:2]=1[O:1][S:14]([CH3:13])(=[O:16])=[O:15]
Reactant: CS(=O)(=O)Cl
Reactant: COC(=O)c1ccc(C)c(O)c1
Solvent: c1ccncc1
Product: COC(=O)c1ccc(C)c(OS(C)(=O)=O)c1
Temperature: 0 °C
Yield: 93 %

Procedure:
To a solution of methyl 3-hydroxy-4-methylbenzoate (3.0 g, 18.1 mmol) in pyridine (20 mL) was added methanesulfonyl chloride (2.80 mL, 36.1 mmol) under stirring at 0° C., and the mixture was stirred at room temperature for 3 hr. The solvent was evaporated under reduced pressure, and the residue was partitioned between ethyl acetate and 1 N hydrochloric acid. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=9/1-hexane/ethyl acetate=1/1) to give the title compound (4.11 g, yield 93%) as a yellow oil.
Reaction SMILES: Cl[C:2]1[C:7]([C:8]([O:10][CH3:11])=[O:9])=[CH:6][N:5]=[C:4]([Cl:12])[CH:3]=1.[O-:13][CH2:14]C.[Na+]>C1COCC1>[Cl:12][C:4]1[CH:3]=[C:2]([O:13][CH3:14])[C:7]([C:8]([O:10][CH3:11])=[O:9])=[CH:6][N:5]=1
Reactant: CC[O-]
Reactant: COC(=O)c1cnc(Cl)cc1Cl
Agent: [Na+]
Solvent: C1CCOC1
Product: COC(=O)c1cnc(Cl)cc1OC
Temperature: 25 °C
Reaction time: 8 h
Yield: 34.8 %

Procedure:
To a mixture of 500 mg of methyl 4,6-dichloronicotinate and 5.0 mL of THF was added dropwise 157 mg of sodium ethoxide (28 wt % of methanol solution) under cooling in an ice bath. It was warmed to room temperature, followed by stirring overnight. The reaction mixture was concentrated under reduced pressure, and the residue was then purified by silica gel column chromatography to obtain 162 mg of methyl 6-chloro-4-methoxynicotinate as a white solid.
Reaction SMILES: C([Sn:9]([Cl:19])([Cl:18])[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH3:17])CCCCCCC.C([Cl:28])CCCCCCC>>[CH2:10]([Sn:9]([Cl:18])([Cl:19])[Cl:28])[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH3:17]
Reactant: CCCCCCCCCl
Reactant: CCCCCCCC[Sn](Cl)(Cl)CCCCCCCC
Product: CCCCCCCC[Sn](Cl)(Cl)Cl

Procedure:
Following the procedure outlined in Example 1, except that di-n-octyltin dichloride is used in place of dimethyltin dichloride, n-octyl chloride in place of methyl chloride, and tetramethylenemethylsulfonium iodide in place of trimethylsulfonium iodide, there is obtained n-octyltin trichloride.
Reaction SMILES: [CH2:1]([OH:12])[C@H:2]([C@H:4]([C@@H:6]([C@@H:8]([CH2:10][OH:11])[OH:9])[OH:7])[OH:5])[OH:3].OP(O)(O)=O.[OH2:18]>>[CH2:10]([OH:11])[C@H:8]1[O:9][C@H:1]([O:12][C@:8]2([CH2:10][OH:11])[O:18][C@H:2]([CH2:1][OH:12])[C@@H:4]([OH:5])[C@@H:6]2[OH:7])[C@H:2]([OH:3])[C@@H:4]([OH:5])[C@@H:6]1[OH:7]
Reactant: O
Reactant: OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO
Agent: O=P(O)(O)O
Product: OC[C@H]1O[C@@](CO)(O[C@H]2O[C@H](CO)[C@@H](O)[C@H](O)[C@H]2O)[C@@H](O)[C@@H]1O

Procedure:
Mannitol (45.0 g) and H3PO4 (1.96 g) are dissolved into water for injectables (800 ml) in order to obtain the starting saccharose solution.
Reaction SMILES: Br[C:2]1[N:7]=[C:6](/[CH:8]=[C:9](\[C:31]#[N:32])/[C:10]([NH:12][CH:13]([C:17]2[CH:22]=[CH:21][C:20](OCCN(CC)CC)=[CH:19][CH:18]=2)[CH2:14][CH2:15][CH3:16])=[O:11])[CH:5]=[CH:4][CH:3]=1.[F:33]C1N=C(C=O)C=CC=1.C(CC(N[C@H](C1C=CC=CC=1)CCC)=O)#N>>[C:31](/[C:9](=[CH:8]\[C:6]1[CH:5]=[CH:4][CH:3]=[C:2]([F:33])[N:7]=1)/[C:10]([NH:12][C@H:13]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[CH2:14][CH2:15][CH3:16])=[O:11])#[N:32]
Reactant: O=Cc1cccc(F)n1
Reactant: CCCC(NC(=O)/C(C#N)=C/c1cccc(Br)n1)c1ccc(OCCN(CC)CC)cc1
Agent: CCC[C@H](NC(=O)CC#N)c1ccccc1
Product: CCC[C@H](NC(=O)/C(C#N)=C/c1cccc(F)n1)c1ccccc1

Procedure:
The title compound was prepared by using a similar procedure as described for the preparation of 33 except that 6-fluoropicolinaldehyde was used instead of 6-bromopicolinaldehyde, and (S)-2-cyano-N-(1-phenylbutyl)acetamide was used instead of 2-cyano-N-(1-(4-(2-(diethylamino)ethoxy)phenyl)butyl)acetamide (29), This produced the crude product which was purified by flash silica gel column chromatography, eluting with 8:2 hexanes/ethyl acetate, to give 40 (115 mg, 96%) as a clear oil: MS (ES+) m/z 324.1 (M+H)+.
Reaction SMILES: Br[C:2]1[N:10]2[C:5]([CH:6]=[N:7][C:8]([NH:11][C:12]3[CH:17]=[CH:16][C:15]([N:18]4[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]4)=[CH:14][CH:13]=3)=[N:9]2)=[CH:4][CH:3]=1.[OH:25][CH2:26][C:27]1[CH:32]=[CH:31][C:30](B(O)O)=[CH:29][CH:28]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CN(C)C=O.O1CCOCC1.C(=O)([O-])[O-].[Na+].[Na+].O>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:24][N:21]1[CH2:20][CH2:19][N:18]([C:15]2[CH:14]=[CH:13][C:12]([NH:11][C:8]3[N:7]=[CH:6][C:5]4=[CH:4][CH:3]=[C:2]([C:30]5[CH:31]=[CH:32][C:27]([CH2:26][OH:25])=[CH:28][CH:29]=5)[N:10]4[N:9]=3)=[CH:17][CH:16]=2)[CH2:23][CH2:22]1
Reactant: OCc1ccc(B(O)O)cc1
Reactant: CN1CCN(c2ccc(Nc3ncc4ccc(Br)n4n3)cc2)CC1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: O=C([O-])[O-]
Solvent: C1COCCO1
Solvent: CN(C)C=O
Solvent: O
Product: CN1CCN(c2ccc(Nc3ncc4ccc(-c5ccc(CO)cc5)n4n3)cc2)CC1
Temperature: 90 °C
Yield: 81.4 %

Procedure:
(7-Bromo-pyrrolo[2,1-f][1,2,4]triazin-2-yl)-[4-(4-methyl-piperazin-1-yl)-phenyl]-amine (0.125 g, 0.323 mmol), (4-Hydroxymethylphenyl)boronic acid (98.1 mg, 0.646 mmol), Triphenylphosphine (24 mg, 0.090 mmol) and Palladium Acetate (7.2 mg, 0.032 mmol) were placed in a vial and purged with vac/N2. N,N-Dimethylformamide (10.0 mL, 129 mmol), 1,4-Dioxane (3.0 mL, 38 mmol) and 2.00 M of Sodium carbonate in Water (1.50 mL, 3.00 mmol) were added and the mixture again purged (vac/N2) before being heated to 90° C. for 4 h. HPLC showed complete consumption of s.m. and LCMS showed m/z=415. Cool and partition between water:DCM (1:1, 60 mL). Sept., ext. aq. with 30 mL DCM. Wash comb. org. with brine (30 mL) and dry (sodium sulfate), filt. and conc. Chromatograph residue on ISCO (DCM load, 0-15% MeOH:DCM, 2×12 g silica) to afford (4-{2-[4-(4-Methyl-piperazin-1-yl)-phenylamino]-pyrrolo[2,1-f][1,2,4]triazin-7-yl}-phenyl)-methanol (109 mg; Yield=81.5). LCMS (HPLC): 0.73 min, m/z=415 (M+H); 1H-NMR (DMSO-d6): 9.20 (s, 1H), 8.92 (s, 1H), 8.17 (d, 2H, J=8.2 Hz), 7.63 (d, 2H, J=9.0 Hz), 7.47 (d, 2H, J=8.2 Hz), 7.15 (d, 1H, J=4.8 Hz), 6.92 (m, 3H), 5.25 (t, 1H, J=5.8 Hz), 4.58 (d, 2H, J=5.8 Hz), 3.09 (m, 4H), 2.47 (m, 4H), 2.23 (s, 3H).
Reaction SMILES: [NH2:1][C:2]1[C:7]([CH3:8])=[CH:6][CH:5]=[CH:4][N:3]=1.C(O[CH:12]=[C:13]([C:19]([O:21][CH2:22][CH3:23])=[O:20])[C:14]([O:16][CH2:17][CH3:18])=[O:15])C>>[CH2:22]([O:21][C:19]([C:13]([C:14]([O:16][CH2:17][CH3:18])=[O:15])=[CH:12][NH:1][C:2]1[C:7]([CH3:8])=[CH:6][CH:5]=[CH:4][N:3]=1)=[O:20])[CH3:23]
Reactant: CCOC=C(C(=O)OCC)C(=O)OCC
Reactant: Cc1cccnc1N
Product: CCOC(=O)C(=CNc1ncccc1C)C(=O)OCC
Temperature: 135 °C
Yield: 74.1 %

Procedure:
A mixture of 2-amino-3-methylpyridine (5.5 g) and 2-ethoxy-1,1-bis(ethoxycarbonyl)ethene (10.8 g) was heated in a heating bath at 135° C. for 30 minutes. It was then cooled and triturated with light petroleum ether (b.p. 40°-60° C.). The resulting crude solid was recrystallised from light petroleum ether (b.p. 40°-60° C.), to give 1,1-bis(ethoxycarbonyl)-2-(3-methylpyrid-2-ylamino)ethene (10.3 g), m.p. 65°-67° C.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]2[C:8]3[C:9]([NH:17][CH2:18][C:19]4[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=4)=[N:10][CH:11]=[C:12]([C:15]#[N:16])[C:13]=3[S:14][C:4]=2[CH:3]=1.Cl.[CH3:28][N:29]([CH2:31][C:32]1[CH:37]=[CH:36][C:35](B(O)O)=[CH:34][CH:33]=1)[CH3:30]>>[CH3:28][N:29]([CH2:31][C:32]1[CH:37]=[CH:36][C:35]([C:2]2[CH:7]=[CH:6][C:5]3[C:8]4[C:9]([NH:17][CH2:18][C:19]5[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=5)=[N:10][CH:11]=[C:12]([C:15]#[N:16])[C:13]=4[S:14][C:4]=3[CH:3]=2)=[CH:34][CH:33]=1)[CH3:30]
Reactant: CN(C)Cc1ccc(B(O)O)cc1
Reactant: COc1ccc(CNc2ncc(C#N)c3sc4cc(Br)ccc4c23)cc1
Agent: Cl
Product: COc1ccc(CNc2ncc(C#N)c3sc4cc(-c5ccc(CN(C)C)cc5)ccc4c23)cc1

Procedure:
The title compound was prepared by the method described in Example 19, Step 1 using 7-bromo-1-[(4-methoxybenzyl)amino][1]benzothieno[3,2-c]pyridine-4-carbonitrile Example 12, Steep 9) and {4-[(dimethylamino)methyl]phenyl}boronic acid hydrochloride.
Reaction SMILES: [C:1]1([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH2:7][C:8]1[NH:9][C:10](=[O:19])[C:11]([OH:18])=[C:12]([C:14](OC)=[O:15])[N:13]=1.[NH:26]1[CH2:30][CH2:29][CH2:28][CH2:27]1>>[C:1]1([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH2:7][C:8]1[NH:9][C:10](=[O:19])[C:11]([OH:18])=[C:12]([C:14]([N:26]2[CH2:30][CH2:29][CH2:28][CH2:27]2)=[O:15])[N:13]=1
Reactant: C1CCNC1
Reactant: COC(=O)c1nc(Cc2ccccc2-c2ccccc2)[nH]c(=O)c1O
Product: O=C(c1nc(Cc2ccccc2-c2ccccc2)[nH]c(=O)c1O)N1CCCC1
Yield: 52.7 %

Procedure:
The synthesis was performed as in Example 21 using methyl 2-(biphenyl-2-ylmethyl)-5-hydroxy-6-oxo-1,6-dihydropyrimidine-4-carboxylate (0.10 g, 298 μmol) and pyrrolidine (0.5 ml; 6.06 mmol) to provide the title compound as an off-white solid (0.059 g; 54%). LCMS: m/z=412 (MH+). LCMS: m/z=375 (MH+).
Reaction SMILES: C(C1C=C([C:15]2[C:16]([O:21][CH3:22])=[N:17][CH:18]=[CH:19][CH:20]=2)C=CC=1OC(F)F)(C)(C)C.[CH3:23][CH2:24]OC(C)=O>CCO.[Pd]>[CH2:23]([C:18]1[CH:19]=[CH:20][CH:15]=[C:16]([O:21][CH3:22])[N:17]=1)[CH3:24]
Reactant: COc1ncccc1-c1ccc(OC(F)F)c(C(C)(C)C)c1
Reactant: CCOC(C)=O
Agent: [Pd]
Solvent: CCO
Product: CCc1cccc(OC)n1
Reaction time: 0.75 h

Procedure:
step 2—A mixture of 22 (1.95 g) and Pd/C (10% wt. on carbon, 50 mg) in EtOAc (15 mL) and EtOH (15 mL) at RT was stirred under 1 atmosphere of H2 for 45 min. The catalyst was filtered off and the filtrate was concentrated. The crude residue was purified by SiO2 chromatography eluting with a EtOAc/hexane gradient (0 to 5% EtOAc) to afford 560 mg of 2-ethyl-6-methoxypyridine (26) as a colorless oil.
Reaction SMILES: [C:1]([C:3]1[CH:4]=[N:5][N:6]2[C:11]([C:12]([F:15])([F:14])[F:13])=[CH:10][C:9]([C:16]3[CH:21]=[CH:20][C:19]([C:22]([F:25])([F:24])[F:23])=[CH:18][CH:17]=3)=[N:8][C:7]=12)#[CH:2].C(OC(=O)[NH:32][CH2:33][CH2:34][NH:35][S:36]([C:39]1[S:40][C:41](Br)=[CH:42][CH:43]=1)(=[O:38])=[O:37])(C)(C)C.C(O)(C(F)(F)F)=O>ClCCl>[NH2:32][CH2:33][CH2:34][NH:35][S:36]([C:39]1[S:40][C:41]([C:2]#[C:1][C:3]2[CH:4]=[N:5][N:6]3[C:11]([C:12]([F:14])([F:13])[F:15])=[CH:10][C:9]([C:16]4[CH:21]=[CH:20][C:19]([C:22]([F:25])([F:24])[F:23])=[CH:18][CH:17]=4)=[N:8][C:7]=23)=[CH:42][CH:43]=1)(=[O:38])=[O:37]
Reactant: C#Cc1cnn2c(C(F)(F)F)cc(-c3ccc(C(F)(F)F)cc3)nc12
Reactant: CC(C)(C)OC(=O)NCCNS(=O)(=O)c1ccc(Br)s1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: NCCNS(=O)(=O)c1ccc(C#Cc2cnn3c(C(F)(F)F)cc(-c4ccc(C(F)(F)F)cc4)nc23)s1

Procedure:
The title compound was prepared from 3-ethynyl-7-trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine (example C.1) (178 mg, 0.5 mmol) and [2-(5-bromo-thiophene-2-sulfonylamino)-ethyl]-carbamic acid tert-butyl ester (example B.51) (193 mg, 0.5 mmol) according to general procedure II and subsequent cleavage of the protecting group with TFA in dichloromethane at 0° C. Obtained as an orange solid (158 mg, 56%). MS (ISN) 558.0 [(M−H)−]; mp 161° C.
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:17]3[C:12](=[CH:13][C:14]([S:18]([NH:21][C:22]4[CH:27]=[CH:26][N:25]=[CH:24][N:23]=4)(=[O:20])=[O:19])=[CH:15][CH:16]=3)[CH:11]=[CH:10][N:9]=2)=[C:4]([O:28][CH3:29])[CH:3]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.[I-].[CH2:60]([Zn+])[C:61]([CH3:64])([CH3:63])[CH3:62]>CO.CO.C(Cl)Cl.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:29][O:28][C:4]1[CH:3]=[C:2]([CH2:60][C:61]([CH3:64])([CH3:63])[CH3:62])[CH:7]=[CH:6][C:5]=1[C:8]1[C:17]2[C:12](=[CH:13][C:14]([S:18]([NH:21][C:22]3[CH:27]=[CH:26][N:25]=[CH:24][N:23]=3)(=[O:20])=[O:19])=[CH:15][CH:16]=2)[CH:11]=[CH:10][N:9]=1
Reactant: CC(C)(C)C[Zn+]
Reactant: COc1cc(Cl)ccc1-c1nccc2cc(S(=O)(=O)Nc3ccncn3)ccc12
Agent: [Pd]
Agent: COc1cccc(OC)c1-c1ccccc1P(C1CCCCC1)C1CCCCC1
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Solvent: CO
Solvent: ClCCl
Product: COc1cc(CC(C)(C)C)ccc1-c1nccc2cc(S(=O)(=O)Nc3ccncn3)ccc12
Temperature: 70 °C
Yield: 32.5 %

Procedure:
A vial was charged with 1-(4-chloro-2-methoxyphenyl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide (EXAMPLE 160; 67 mg, 0.157 mmol), dicyclohexyl(2′,6′-dimethoxy-[1,1′-biphenyl]-2-yl)phosphine (6.44 mg, 0.016 mmol), and Pd2(dba)3 (7.19 mg, 7.85 mmol). The vial was flushed with Ar (g), then neopentylzinc(II) iodide (0.5 M in THF) (1570 μl, 0.785 mmol) was added. The mixture was sonicated for 30 s to give a suspension. The sealed vial was heated to 70° C. for 2 h then 90° C. overnight. The mixture was diluted with MeOH, filtered through Celite, and concentrated. The residue was purified by chromatography on silica gel (12-g Redi-Sep Gold column, 0-7.5% MeOH/DCM) to give a yellow foam. The material was dissolved in MeOH/DCM and loaded onto a 2-g SCX-2 ion exchange column. The filtrate was concentrated, and the residue was purified by chromatography on silica gel (25-g Interchim 15 micron column, 3.5% MeOH/DCM) to give 1-(2-methoxy-4-neopentylphenyl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide (23.65 mg, 0.051 mmol, 32.6% yield) as a light-yellow solid. 1H NMR (400 MHz, DMSO-d6) δ=13.07 (br. s, 1H), 8.70-8.61 (m, 2H), 8.57 (s, 1H), 8.24 (br. s., 1H), 8.06 (d, J=5.8 Hz, 1H), 7.94 (dd, J=1.7, 8.9 Hz, 1H), 7.71 (d, J=8.8 Hz, 1H), 7.22 (d, J=7.6 Hz, 1H), 7.03 (br. s., 1H), 6.96 (s, 1H), 6.89 (d, J=7.6 Hz, 1H), 3.62 (s, 3H), 2.60 (s, 2H), 0.97 (s, 9H). m/z (ESI) 463.2 (M+H)+.
Reaction SMILES: [CH2:1]([N:5]([CH2:15][CH2:16][CH2:17][CH3:18])[C:6]([C:8]1[C:12](Cl)=[C:11]([CH3:14])[NH:10][N:9]=1)=[O:7])[CH2:2][CH2:3][CH3:4].[O:19]1[CH2:24][CH2:23][CH2:22][CH2:21][CH:20]1[O:25][CH2:26]CC1NN=C(C(OCC)=O)C=1>>[CH2:1]([N:5]([CH2:15][CH2:16][CH2:17][CH3:18])[C:6]([C:8]1[CH:12]=[C:11]([CH2:14][CH2:26][O:25][CH:20]2[CH2:21][CH2:22][CH2:23][CH2:24][O:19]2)[NH:10][N:9]=1)=[O:7])[CH2:2][CH2:3][CH3:4]
Reactant: CCCCN(CCCC)C(=O)c1n[nH]c(C)c1Cl
Reactant: CCOC(=O)c1cc(CCOC2CCCCO2)[nH]n1
Product: CCCCN(CCCC)C(=O)c1cc(CCOC2CCCCO2)[nH]n1
Yield: 83 %

Procedure:
Following a procedure analogous to that for the synthesis of Intermediate 1B, ethyl 5-(2-(tetrahydro-2H-pyran-2-yloxy)ethyl)-1H-pyrazole-3-carboxylate (2.15 g, 8.01 mmol) was converted to the title compound (2.35 g, 83%). MS(ESI+) m/z 352.4 (M+H)+.
Reaction SMILES: I[C:2]1[C:7]([O:8][C:9]2[C:18]3[C:13](=[CH:14][C:15]([O:21][CH3:22])=[C:16]([O:19][CH3:20])[CH:17]=3)[N:12]=[CH:11][CH:10]=2)=[CH:6][CH:5]=[C:4]([CH3:23])[N:3]=1.[S:24]1[CH:28]=[CH:27][C:26](B(O)O)=[CH:25]1.C(=O)([O-])O.[Na+]>C1(C)C=CC=CC=1>[CH3:20][O:19][C:16]1[CH:17]=[C:18]2[C:13](=[CH:14][C:15]=1[O:21][CH3:22])[N:12]=[CH:11][CH:10]=[C:9]2[O:8][C:7]1[C:2]([C:26]2[CH:27]=[CH:28][S:24][CH:25]=2)=[N:3][C:4]([CH3:23])=[CH:5][CH:6]=1
Reactant: OB(O)c1ccsc1
Reactant: COc1cc2nccc(Oc3ccc(C)nc3I)c2cc1OC
Agent: O=C([O-])O
Agent: [Na+]
Solvent: Cc1ccccc1
Product: COc1cc2nccc(Oc3ccc(C)nc3-c3ccsc3)c2cc1OC
Temperature: 80 °C
Reaction time: 3 h
Yield: 77 %

Procedure:
4-[(2-Iodo-6-methyl-3-pyridyl)oxy]-6,7-dimethoxyquinoline (compound 116) (84 mg), 3-thiopheneboronic acid (128 mg), and tetrakistriphenylphosphine palladium (12 mg) were dissolved in toluene (1 ml) to prepare a solution. A saturated aqueous sodium hydrogencarbonate solution (1 ml) was added to the solution, and the mixture was stirred at 80° C. for 3 hr. The reaction solution was filtered, the solvent was then removed by distillation under the reduced pressure, and the residue was purified by column chromatography using methanol-chloroform to give the title compound (58 mg, yield 77%).
Reaction SMILES: [Li].[O:2]([CH2:5][CH3:6])CC.IC.[CH3:9][CH:10]([N:12]1[CH2:17][CH2:16][C:15]([NH:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)(C(O)=O)[CH2:14][CH2:13]1)[CH3:11]>O>[CH3:11][CH:10]([N:12]1[CH2:17][CH2:16][C:15]([C:5](=[O:2])[CH3:6])([NH:21][C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=2)[CH2:14][CH2:13]1)[CH3:9]
Reactant: CC(C)N1CCC(Nc2ccccc2)(C(=O)O)CC1
Reactant: CCOCC
Agent: [Li]
Solvent: CI
Solvent: O
Product: CC(=O)C1(Nc2ccccc2)CCN(C(C)C)CC1
Temperature: 5 °C
Reaction time: 1.5 h
Yield: 33.5 %

Procedure:
To a stirred mixture of 13.8 parts of lithium and 140 parts of 1,1'-oxybisethane is added dropwise a mixture of 156 parts of iodomethane and 140 parts of 1,1'-oxybisethane while nitrogen gas is introduced. After the addition is complete, there are added 420 parts of 1,1'-oxybisethane and stirring is continued at reflux temperature till all lithium has reacted (about 15 minutes). Then there are added portionwise 26.25 parts of 1-(1-methylethyl)-4-(phenylamino)-4-piperidinecarboxylic acid (exothermic reaction: reflux temperature is maintained) while nitrogen gas is still introduced. Upon completion, stirring at reflux is continued for 1.50 hours. After the nitrogen gas introduction is stopped, the reaction mixture is cooled to 5° C. and decomposed by pouring onto 600 parts of water. The organic phase is separated, washed with water, dried, filtered and evaporated. The residue is purified by column-chromatography over silica gel using a mixture of trichloromethane and methanol (95:5 by volume), saturated with ammonia, as eluent. The pure fractions are collected and the eluent is evaporated. The residue is crystallized from petroleumether at 0° C. The product is filtered off and dried, yielding 8.7 parts (33.5%) of 1-[1-(1-methylethyl)-4-(phenylamino)-4-piperidinyl]ethanone; mp. 107.1° C.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[S:10][CH3:11])[CH:5]=[O:6].[CH:12]([C:14]([CH3:16])=[O:15])=[CH2:13].CCN(CC)CC>C(O)C.[Cl-].C([N+]1C(C)=C(CCO)SC=1)C1C=CC=CC=1>[F:1][C:2]1[CH:3]=[C:4]([C:5](=[O:6])[CH2:13][CH2:12][C:14](=[O:15])[CH3:16])[CH:7]=[CH:8][C:9]=1[S:10][CH3:11]
Reactant: C=CC(C)=O
Reactant: CSc1ccc(C=O)cc1F
Agent: Cc1c(CCO)sc[n+]1Cc1ccccc1
Agent: [Cl-]
Solvent: CCN(CC)CC
Solvent: CCO
Product: CSc1ccc(C(=O)CCC(C)=O)cc1F
Reaction time: 2 h
Yield: 72.5 %

Procedure:
To a stirred solution of 3-fluoro-4-(methylthio)benzaldehyde (3.04 g, 17.9 mmol) in ethanol (12 mL) was added methyl vinyl ketone (1.3 mL, 15.5 mmol), 3-benzyl-5-(2-hydroxyethyl)-4-methylthiazolium chloride (0.84 g, 3.1 mmol), and Et3N (4.32 mL, 31 mmol) at room temperature. After stirring for 2 hours, volatiles were removed by evaporation. The residue was taken up with ethyl acetate (200 mL), and washed with water (120 mL), dil. aqueous HCl (120 mL), water (120 mL), brine (120 mL), dried over MgSO4, and concentrated in vacuo. The resulting crude residue was purified by flash chromatography on silica gel eluting with ethyl acetate/hexane (1/2) to provide 1-[3-fluoro-4-(methylthio)phenyl]pentane-1,4-dione (2.7 g, 73% yield). To a stirred suspension of 1-[3-fluoro-4-(methylthio)phenyl]pentane-1,4-dione (2.7 g, 11.25 mmol) in methanol (50 mL) was added Oxone (14.14 g, 23 mmol) in water (50 mL) at room temperature. After stirring for 5 hours, the mixture was diluted with water. The whole was extracted with CH2Cl2 (50 mL×4), the combined organic layer washed with brine, dried over MgSO4, and evaporated in vacuo to give the subtitle compound (2.8 g, 66% yield).
Reaction SMILES: C([O:3][C:4]([C:6]1[CH:7]=[N:8][N:9]([C:11]2[C:16]([NH:17][S:18]([C:21]3[CH:26]=[CH:25][C:24]([C:27]([CH3:30])([CH3:29])[CH3:28])=[CH:23][CH:22]=3)(=[O:20])=[O:19])=[CH:15][C:14]([Cl:31])=[CH:13][N:12]=2)[CH:10]=1)=[O:5])C.[OH-].[Na+].C1COCC1>C(O)(=O)C>[C:27]([C:24]1[CH:25]=[CH:26][C:21]([S:18]([NH:17][C:16]2[C:11]([N:9]3[CH:10]=[C:6]([C:4]([OH:5])=[O:3])[CH:7]=[N:8]3)=[N:12][CH:13]=[C:14]([Cl:31])[CH:15]=2)(=[O:19])=[O:20])=[CH:22][CH:23]=1)([CH3:30])([CH3:28])[CH3:29]
Reactant: CCOC(=O)c1cnn(-c2ncc(Cl)cc2NS(=O)(=O)c2ccc(C(C)(C)C)cc2)c1
Agent: [Na+]
Agent: [OH-]
Solvent: CC(=O)O
Solvent: C1CCOC1
Product: CC(C)(C)c1ccc(S(=O)(=O)Nc2cc(Cl)cnc2-n2cc(C(=O)O)cn2)cc1
Temperature: 80 °C
Reaction time: 16 h

Procedure:
A 25 mL scintillation vial was charged with 1-[3-(4-tert-butyl-benzenesulfonylamino)-5-chloro-pyridin-2-yl]-1H-pyrazole-4-carboxylic acid ethyl ester (synthesized according to general procedure D, 93 mg, 0.2 mmol), NaOH (2 mL, 1.0 M solution in water), and THF (3 mL). The vial was sealed and stirred at 80° C. for 16 hours. The reaction solution was subsequently neutralized to pH=5 with glacial acetic acid. The mixture was extracted with ethyl acetate (2×10 mL) and the combined organics were concentrated in vacuo. The resultant residue was purified via preparative HPLC to afford 1-[3-(4-tert-butyl-benzenesulfonylamino)-5-chloro-pyridin-2-yl]-1H-pyrazole-4-carboxylic acid as a white powder: MS (ES) M+H expected 435.1, found 435.0.
Reaction SMILES: OC1C=CC([C:8]([C:16]2[CH:21]=[CH:20][C:19]([OH:22])=[CH:18]C=2)([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)C)=CC=1.C(Cl)(=O)C1C=CC=C(C(Cl)=[O:28])C=1>>[CH:12]1[CH:11]=[C:10]([C:8]2[CH:16]=[CH:21][CH:20]=[C:19]([OH:22])[CH:18]=2)[C:15]([OH:28])=[CH:14][CH:13]=1
Reactant: CC(c1ccccc1)(c1ccc(O)cc1)c1ccc(O)cc1
Reactant: O=C(Cl)c1cccc(C(=O)Cl)c1
Product: Oc1cccc(-c2ccccc2O)c1

Procedure:
A polyester of 1,1-bis-(4-hydroxy-phenyl)-1-phenyl-ethane (diphenol B) and an equimolar mixture of isophthaloyl chloride and terephthaloychloride were reacted in a two-phase boundary surface to form a diphenol B polyester with an η inh.=0.76 dl/g. 1.9 kg of the said polyester were dissolved in 8.1 mg of 1,2-dichloroethane to obtain 10 kg of a spinning solution with a FB viscosity of 63 s/400 mm. The spinning procedure of Example 1 was repeated with the spinning solution to obtain individual fibers with the following properties: titer of 2.5 den; elasticity modulus of 1.41×106N/cm2 ; tensile strength of 1.03×104N/cm2 (0.97 g/den); and tear elongation of 7.8%.