Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([OH:10])[CH:7]=[CH:8][CH:9]=1)([O-:3])=[O:2].Br[CH2:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[CH:15][CH:14]=1.C(=O)([O-])[O-].[K+].[K+]>CC(C)=O>[N+:1]([C:4]1[CH:5]=[C:6]([CH:7]=[CH:8][CH:9]=1)[O:10][CH2:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)=[CH:15][CH:14]=1)([O-:3])=[O:2]
Reactant: O=[N+]([O-])c1cccc(O)c1
Reactant: BrCc1ccc(-c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: O=[N+]([O-])c1cccc(OCc2ccc(-c3ccccc3)cc2)c1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
A mixture of 3-Nitro-phenol (3.5 g, 25 mmole), 4-Bromomethyl-biphenyl (4.94 g, 20 mmole) and Potassium carbonate (3.8 g, 30 mmole) in 75 mL of acetone is stirred for 16 hr at room temperature. After removal of the solvent, the residue is taken up in ethyl acetate, washed with 1 N NaOH and brine, dried over Na2SO4, and concentrated to yield a solid. The solid is washed with methanol and dried under vacuum to afford 4-(3-Nitro-phenoxymethyl)-biphenyl.
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][NH:4][C:3]2[N:7]=[CH:8][CH:9]=[CH:10][C:2]1=2.[C:11](Cl)(=[O:18])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1>>[N:1]1([C:11]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[O:18])[CH2:6][CH2:5][NH:4][C:3]2[N:7]=[CH:8][CH:9]=[CH:10][C:2]1=2
Reactant: O=C(Cl)c1ccccc1
Reactant: c1cnc2c(c1)NCCN2
Product: O=C(c1ccccc1)N1CCNc2ncccc21
Yield: 10 %

Procedure:
1,2,3,4-tetrahydropyrido[2,3-b]pyrazine was reacted with benzoyl chloride as in General Procedure 2 to give the title compound as a beige solid (<10% yield). M.p. 166-168° C., LCMS: m/z=240.12 (M+H+), 1H-NMR (DMSO-d6, 400 MHz) δ 3.45-3.49 (m, 2H), 3.84-3.87 (m, 2H), 6.40 (s, 1H), 6.77 (dd, J=4.8 Hz, 4.5 Hz, 1H), 6.92 (dd, J=1.5 Hz, 7.8 Hz, 1H), 7.10 (dd, J=1.5 Hz, 4.6 Hz, 1H), 7.25-7.34 (m, 5H).
Reaction SMILES: I[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[O:8][CH3:9].[C:10]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[NH:18][C:19](=[O:21])[CH3:20])#[CH:11]>>[CH3:9][O:8][C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1[C:11]1[N:18]([C:19](=[O:21])[CH3:20])[C:13]2[C:12]([CH:10]=1)=[CH:17][CH:16]=[CH:15][CH:14]=2
Reactant: C#Cc1ccccc1NC(C)=O
Reactant: COc1ccccc1I
Product: COc1ccccc1-c1cc2ccccc2n1C(C)=O
Yield: 83 %

Procedure:
The general procedure was used to convert 1-iodo-2-methoxybenzene and N-(2-ethynylphenyl)acetamide to the title product. Purification by flash chromatography gave the analytically pure product as a slightly yellow solid, 83% yield. 1H NMR (300 MHz, CDCl3) δ 8.40-8.36 (m, 1H), 7.57-7.53 (m, 1H), 7.45-7.41 (m, 2H), 7.36-7.22 (m, 2H), 7.09-7.04 (m, 1H) 6.95-6.92 (m, 1H), 6.54 (s, 1H), 3.76 (s, 3H), 2.10 (s, 3H). 13C NMR (75 MHz, CDCl3) δ 171.26, 156.93, 137.29, 136.39, 130.66, 130.55, 129.06, 124.76, 123.43, 123.16, 121.04, 120.21, 116.07, 111.30, 110.65, 55.38, 25.80.
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[C:10]([NH:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[F:18])=[C:9]([F:19])[C:8](Cl)=[C:7]([C:21]#[N:22])[N:6]=1)=[O:4].[K].CC(=[N:27][NH2:28])C.CC(=NO)C>>[CH3:1][O:2][C:3]([C:5]1[C:10]([NH:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[F:18])=[C:9]([F:19])[C:8]2[C:7](=[C:21]([NH2:22])[NH:27][N:28]=2)[N:6]=1)=[O:4]
Reactant: CC(C)=NN
Reactant: COC(=O)c1nc(C#N)c(Cl)c(F)c1Nc1ccccc1F
Agent: CC(C)=NO
Agent: [K]
Product: COC(=O)c1nc2c(N)[nH]nc2c(F)c1Nc1ccccc1F

Procedure:
The title compound is prepared from 5-chloro-6-cyano-4-fluoro-3-(2-fluorophenylamino)-pyridine-2-carboxylic acid methyl ester (prepared in Example 9) and the potassium salt of acetone hydrazone in place of the potassium salt of acetone oxime by the method previously described in step H of Example 8.
Reaction SMILES: [Cl:1][C:2]1[C:3]([C:12](=[N:27][O:28][CH2:29][CH3:30])[CH2:13][NH:14][C:15](=[O:26])[C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[C:22]([F:25])([F:24])[F:23])=[N:4][CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1.C(C1C=CC=CC=1)(=O)C1C=CC=CC=1>C(#N)C>[Cl:1][C:2]1[C:3](/[C:12](=[N:27]\[O:28][CH2:29][CH3:30])/[CH2:13][NH:14][C:15](=[O:26])[C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[C:22]([F:24])([F:25])[F:23])=[N:4][CH:5]=[C:6]([C:8]([F:9])([F:11])[F:10])[CH:7]=1
Reactant: CCON=C(CNC(=O)c1ccccc1C(F)(F)F)c1ncc(C(F)(F)F)cc1Cl
Agent: O=C(c1ccccc1)c1ccccc1
Solvent: CC#N
Product: CCO/N=C(/CNC(=O)c1ccccc1C(F)(F)F)c1ncc(C(F)(F)F)cc1Cl
Yield: 87.5 %

Procedure:
To 48 mg of N-[2-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]-2-(ethoxyimino)ethyl]-2-(trifluoromethyl)benzamide in 3 ml of acetonitrile, 1 mg of benzophenone was added, and the mixture was irradiated with light for 4 hours in a quartz cell (manufactured by Fine, 4 clear windows for spectroscopy) using a 100 W high-pressure mercury lamp (manufactured by USHIO INC., lamp: UM-102, power supply: UM-103B-B). After completion of the reaction, the solvent was evaporated under reduced pressure, and the resulting residue was purified by silica gel column chromatography using ethyl acetate-hexane (with a gradient of from 1:9 to 5:5) as the eluent to obtain 42 mg of the desired product as white crystals.
Reaction SMILES: C([O:4][CH:5]([C:13]1[CH:21]=[C:20]2[C:16]([CH:17]=[CH:18][CH2:19]2)=[CH:15][CH:14]=1)[CH2:6][O:7][CH2:8][CH2:9][N:10]([CH3:12])[CH3:11])(=O)C.C[O-].[Na+].CO.[ClH:27].C(O)C>CO.C(O)C>[ClH:27].[CH2:19]1[C:20]2[C:16](=[CH:15][CH:14]=[C:13]([CH:5]([OH:4])[CH2:6][O:7][CH2:8][CH2:9][N:10]([CH3:11])[CH3:12])[CH:21]=2)[CH:17]=[CH:18]1
Reactant: CC(=O)OC(COCCN(C)C)c1ccc2c(c1)CC=C2
Agent: C[O-]
Agent: Cl
Agent: [Na+]
Solvent: CO
Solvent: CCO
Product: CN(C)CCOCC(O)c1ccc2c(c1)CC=C2
Temperature: 25 °C
Reaction time: 0.33 h

Procedure:
In 0.5 ml of methanol was dissolved 80 mg of 1-acetoxy-1-(1H-inden-6-yl)-2-[2-(N,N-dimethylamino)ethoxy]ethane. To the solution was added 80 mg of a 28% sodium methoxide-methanol solution with ice cooling. The resulting mixture was stirred at room temperature for 20 minutes. The solvent was removed by distillation under reduced pressure. The residue thus obtained was purified by column chromatography (eluant:chloroform/methanol=20/1) to obtain a yellow oily product. The oily product was dissolved in 0.1 ml of ethanol. To the solution was added 0.1 ml of a 5.9N dry hydrogen chloride-ethanol solution at room temperature. The resulting crystals were collected by filtration to obtain 20 mg of 1-(1H-inden-6-yl)-2-[2-(N,N-dimethylamino)ethoxy]ethanol hydrochloride (compound No. 298).
Reaction SMILES: [ClH:1].Cl.[N:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[N:9]([CH2:33][C:34]([O:36]CC)=[O:35])[C:10]([C:12]1[CH:32]=[CH:31][C:15]2[N:16]([CH3:30])[C:17]([CH2:19][NH:20][C:21]3[CH:26]=[CH:25][C:24]([C:27](=[NH:29])[NH2:28])=[CH:23][CH:22]=3)=[N:18][C:14]=2[CH:13]=1)=[O:11].[OH-].[Na+]>>[ClH:1].[N:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[N:9]([CH2:33][C:34]([OH:36])=[O:35])[C:10]([C:12]1[CH:32]=[CH:31][C:15]2[N:16]([CH3:30])[C:17]([CH2:19][NH:20][C:21]3[CH:26]=[CH:25][C:24]([C:27](=[NH:28])[NH2:29])=[CH:23][CH:22]=3)=[N:18][C:14]=2[CH:13]=1)=[O:11]
Reactant: CCOC(=O)CN(C(=O)c1ccc2c(c1)nc(CNc1ccc(C(=N)N)cc1)n2C)c1ccccn1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Product: Cn1c(CNc2ccc(C(=N)N)cc2)nc2cc(C(=O)N(CC(=O)O)c3ccccn3)ccc21
Yield: 91 %

Procedure:
Prepared analogously to Example 26 from 1-methyl-2-[N-(4-amidinophenyl)-aminomethyl]-benzimidazol-5-yl-carboxylic acid-N-(2-pyridyl)-N-(ethoxycarbonylmethyl)-amide-dihydrochloride and sodium hydroxide solution. Yield: 91% of theory, C24H23N7O3 (457.5) ##EQU28##
Reaction SMILES: [F:1][C:2]1[C:11]2[CH2:10][CH2:9][CH2:8][CH2:7][C:6]=2[CH:5]=[CH:4][C:3]=1[CH2:12][O:13][C:14]1[CH:19]=[CH:18][C:17]([C@@H:20]([C:26]2[N:30]([CH3:31])[CH:29]=[N:28][N:27]=2)[CH2:21][C:22]([O:24]C)=[O:23])=[CH:16][CH:15]=1.[Li+].[OH-]>C1COCC1.CCO>[F:1][C:2]1[C:11]2[CH2:10][CH2:9][CH2:8][CH2:7][C:6]=2[CH:5]=[CH:4][C:3]=1[CH2:12][O:13][C:14]1[CH:19]=[CH:18][C:17]([C@@H:20]([C:26]2[N:30]([CH3:31])[CH:29]=[N:28][N:27]=2)[CH2:21][C:22]([OH:24])=[O:23])=[CH:16][CH:15]=1
Reactant: COC(=O)C[C@@H](c1ccc(OCc2ccc3c(c2F)CCCC3)cc1)c1nncn1C
Agent: [Li+]
Agent: [OH-]
Solvent: CCO
Solvent: C1CCOC1
Product: Cn1cnnc1[C@@H](CC(=O)O)c1ccc(OCc2ccc3c(c2F)CCCC3)cc1
Temperature: 23 °C

Procedure:
To a stirred solution of 47.9 (100 mg, 0.24 mmol) in THF/EtOH (6 mL, 3/1, v/v) is added 1N LiOH (aq) (2 mL). The reaction mixture is stirred at 23° C. until TLC confirms consumption of the starting material. The organic solvent is removed in vacuo. 1N HCl is added to neutralize the mixture to pH 7. The mixture is extracted with EtOAc (2×10 mL), concentrated in vacuo. The residue is purified by column chromatography (silica, MeOH/DCM), to afford acid 47.
Reaction SMILES: O[CH:2]([C:5]1[N:9]([CH2:10][C:11]2[CH:16]=[CH:15][C:14]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[C:23]3[N:27]([C:28]([C:41]4[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=4)([C:35]4[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=4)[C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=4)[N:26]=[N:25][N:24]=3)=[CH:13][CH:12]=2)[C:8]([C:47]([O:49][CH2:50][CH3:51])=[O:48])=[CH:7][CH:6]=1)[CH2:3][CH3:4].C1CCN2C(=NCCC2)CC1.CS(Cl)(=O)=O>C(Cl)Cl>[CH:2]([C:5]1[N:9]([CH2:10][C:11]2[CH:12]=[CH:13][C:14]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[C:23]3[N:27]([C:28]([C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=4)([C:41]4[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=4)[C:35]4[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=4)[N:26]=[N:25][N:24]=3)=[CH:15][CH:16]=2)[C:8]([C:47]([O:49][CH2:50][CH3:51])=[O:48])=[CH:7][CH:6]=1)=[CH:3][CH3:4]
Reactant: CCOC(=O)c1ccc(C(O)CC)n1Cc1ccc(-c2ccccc2-c2nnnn2C(c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: CS(=O)(=O)Cl
Solvent: C1CCC2=NCCCN2CC1
Solvent: ClCCl
Product: CC=Cc1ccc(C(=O)OCC)n1Cc1ccc(-c2ccccc2-c2nnnn2C(c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Reaction time: 24 h

Procedure:
To a solution of ethyl 5-(1-hydroxypropyl)-1-[2'-(1-triphenylmethyltetrazol-5-yl)biphenyl-4yl-methyl]pyrrole-2-carboxylate (2.0 g, 3.0 mmol) in methylene chloride (100 ml) at 0° C. was added DBU (2.0 ml, 12.0 mmol) followed by methanesulfonyl chloride (0.7 ml, 9.0 mmol). The mixture was stirred overnight at room temperature whereupon an additional aliquot of DBU (2.0 ml) and methanesulfonyl chloride (0.7 ml) were added and the mixture was allowed to stir an additional 24 hours. The mixture was poured into a separatory funnel and washed with water (3×50 ml) and saturated aqueous sodium bicarbonate solution (50 ml) before being dried (MgSO4), filtered and concentrated. The crude residue was purified by flash chromatography on silica gel (150 g, 10-30% EtOAc/hexanes) to give the title compounds as a mixture of cis/trans isomers (ca. 1/4).
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([NH2:8])[CH:5]=[CH:4][CH:3]=1.[N:9]1[CH:14]=[CH:13][CH:12]=[C:11](B(O)O)[CH:10]=1.C([O-])([O-])=O.[K+].[K+]>CC([O-])=O.CC([O-])=O.[Pd+2].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=C(S([O-])(=O)=O)C=2OC)CCCCC1.[Na+].O>[N:7]1[C:6]([NH2:8])=[CH:5][CH:4]=[CH:3][C:2]=1[C:11]1[CH:10]=[N:9][CH:14]=[CH:13][CH:12]=1
Reactant: Nc1cccc(Cl)n1
Reactant: OB(O)c1cccnc1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: COc1ccc(S(=O)(=O)[O-])c(OC)c1-c1ccccc1P(C1CCCCC1)C1CCCCC1
Solvent: O
Product: Nc1cccc(-c2cccnc2)n1
Yield: 84.7 %

Procedure:
The general procedure described in Example 3 was used with 6-chloro-pyridin-2-ylamine (129 mg, 1.00 mmol), 3-pyridylboronic acid (184 mg, 1.50 mmol), Pd(OAc)2 (2.2 mg, 0.010 mmol, 1 mol %), sodium 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl-3′-sulfonate (10.0 mg, 0.020 mmol, 2 mol %), K2CO3 (414 mg, 3.00 mmol), water (2.0 mL), 12 h, 100° C. The product was purified by column chromatography on silica gel (eluting with ethyl acetate/methanol, 9.5/0.5) to give the desired product as a white solid (145 mg, 85%). Mp=108° C. 1H NMR (400 MHz, d4-MeOH) δ: 8.69 (d, 1H, J=4.8 Hz), 8.43 (dd, 1H, J=4.8 Hz, 1.6 Hz), 8.19 (d, 1H, J=4.8 Hz), 7.96 (dq, 1H, J=8.0 Hz, 1.6 Hz, 0.4 Hz), 7.75 (dd, 1H, J=8.8 Hz, 2.4 Hz), 7.44 (qd, 1H, J=4.8 Hz, 8.8 Hz), 6.68 (d, 1H, J=8.4 Hz). 13C NMR (125 MHz, d4-MeOH) δ: 161.0, 148.2, 147.4, 146.5, 137.9, 136.0, 135.4, 125.6, 123.4, 110.6. IR (neat, cm−1): 3396 (br), 2522, 1633, 1018. EI-MS: Theoretical [M+H]=172.0869. Found: 172.0868. Anal. Calcd for C10H9N3: C, 70.16; H, 5.30. Found: C, 69.89; H, 5.25.
Reaction SMILES: CC([N:5]([CH2:9][C:10]([NH:12][N:13]1[CH:17]=[CH:16][CH:15]=[C:14]1[Cl:18])=[O:11])C(=O)[O-])(C)C.Cl>CCOC(C)=O.CCOCC>[ClH:18].[NH2:5][CH2:9][C:10]([NH:12][N:13]1[CH:17]=[CH:16][CH:15]=[C:14]1[Cl:18])=[O:11]
Reactant: CC(C)(C)N(CC(=O)Nn1cccc1Cl)C(=O)[O-]
Agent: Cl
Solvent: CCOCC
Solvent: CCOC(C)=O
Product: NCC(=O)Nn1cccc1Cl
Reaction time: 19 h
Yield: 62.8 %

Procedure:
To a stirred solution of 1,1-dimethylethyl-[2-(2-chloro-1H-pyrrol-1-ylamino)-2-oxoethyl]carbamate (3.1 g) in EtOAc (20 ml) and ether (20 ml) was added ethereal HCl (excess) at room temperature. The reaction mixture was allowed to stir for 19 hours at which time the precipitated product was filtered and washed with EtOAc. Recrystallization from ethanol/ether afforded 0.75 g of the product as a solid, m.p. 220° C. (dec.).
Reaction SMILES: [S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[C:3](=[O:10])[NH:2]1.[CH3:11][C:12]1[CH:13]=[C:14]([CH:19]=[CH:20][CH:21]=1)[CH2:15][N:16]=[C:17]=[O:18]>>[CH3:11][C:12]1[CH:13]=[C:14]([CH:19]=[CH:20][CH:21]=1)[CH2:15][NH:16][C:17]([N:2]1[C:3](=[O:10])[C:4]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=2[S:1]1)=[O:18]
Reactant: O=c1[nH]sc2ccccc12
Reactant: Cc1cccc(CN=C=O)c1
Product: Cc1cccc(CNC(=O)n2sc3ccccc3c2=O)c1

Procedure:
Following the synthetic procedure of 6a as described in Example 1, compound 6k (37% yield) was synthesized from benzo[d]isothiazol-3-one and 3-methylbenzyl isocyanate as a white solid. mp 153-155° C.; IR(CHCl3) 3281, 1711, 1650,1534 cm−1; 1H-NMR (DMSO-d6) δ2.28 (s, 3H), 4.49 (d, J=5.9 Hz, 2H), 7.07 (d, J=7.5 Hz, 1H), 7.12-7.16 (m, 2H), 7.22 (t, J=7.5 Hz, 1H), 7.48 (t, J=7.8 Hz, 1H), 7.78 (t, J=8.2 Hz, 1H), 7.93 (d, J=7.8 Hz, 1H), 8.01 (d, J=8.2 Hz, 1H), 9.25 (br t, J=5.9 Hz, 1H); ESIMS m/e 299 (M++1).
Reaction SMILES: [O-:1][CH2:2]C.[Na+].[H-].[Na+].[CH3:7][O:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][C:18]=1[O:19][CH3:20])[N:15]([C:21]([O:23][CH2:24][CH3:25])=[O:22])[CH:14]([CH3:26])[CH2:13][C:12]2=[O:27].C(OCC)=O>C1C=CC=CC=1.C(O)C>[CH3:7][O:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][C:18]=1[O:19][CH3:20])[N:15]([C:21]([O:23][CH2:24][CH3:25])=[O:22])[CH:14]([CH3:26])[C:13](=[CH:2][OH:1])[C:12]2=[O:27]
Reactant: CCOC(=O)N1c2cc(OC)c(OC)cc2C(=O)CC1C
Reactant: CC[O-]
Agent: [H-]
Agent: [Na+]
Solvent: CCOC=O
Solvent: c1ccccc1
Solvent: CCO
Product: CCOC(=O)N1c2cc(OC)c(OC)cc2C(=O)C(=CO)C1C
Temperature: 25 °C
Reaction time: 3 h
Yield: 96 %

Procedure:
To sodium ethoxide, freshly prepared from 4.8 g. of sodium hydride and 6.0 ml. of ethanol was added a solution of 14.7 g. of ethyl 6,7-dimethoxy-2-methyl-4-oxo-1,2,3,4-tetrahydroquinoline-1-carboxylate and 19.8 ml. of ethyl formate in 150 ml. of benzene, over a 45 min. period. The reaction mixture was stirred at room temperature for 3 hrs. and then it was poured onto 250 ml. of ice water. The layers were separated, and the organic layer was extracted with 1N sodium hydroxide solution. The combined aqueous phases were washed with benzene, and then they were added dropwise to 250 ml. of 12N hydrochloric acid. This caused the product to separate in the form of an oil. Recrystallization of this oil from hexane produced 15.4 g. (96% yield) of the title compound, m.p. 98°-101° C. Further recrystallization from hexane raised the melting point to 129°-130° C.
Reaction SMILES: [Br:1][C:2]1[CH:23]=[CH:22][C:21]2[S:20][C:19]3[C:6](=[CH:7][C:8]4[S:9][C:10]5[C:15]([CH:16]([C:24]6[CH:29]=[CH:28][C:27]([CH:30]([CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH3:42])[CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH3:36])=[CH:26][CH:25]=6)[C:17]=4[CH:18]=3)=[CH:14][C:13]([Br:43])=[CH:12][CH:11]=5)[CH:5]([C:44]3[CH:49]=[CH:48][C:47]([CH:50]([CH2:57][CH2:58][CH2:59][CH2:60][CH2:61][CH3:62])[CH2:51][CH2:52][CH2:53][CH2:54][CH2:55][CH3:56])=[CH:46][CH:45]=3)[C:4]=2[CH:3]=1.C1(Cl)C(=O)C(Cl)=C(Cl)C(=O)C=1Cl>CO>[Br:43][C:13]1[CH:12]=[CH:11][C:10]2[S:9][C:8]3[C:17]([CH:18]=[C:19]4[C:6]([CH:7]=3)=[C:5]([C:44]3[CH:49]=[CH:48][C:47]([CH:50]([CH2:51][CH2:52][CH2:53][CH2:54][CH2:55][CH3:56])[CH2:57][CH2:58][CH2:59][CH2:60][CH2:61][CH3:62])=[CH:46][CH:45]=3)[C:4]3[C:21](=[CH:22][CH:23]=[C:2]([Br:1])[CH:3]=3)[S:20]4)=[C:16]([C:24]3[CH:25]=[CH:26][C:27]([CH:30]([CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH3:42])[CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH3:36])=[CH:28][CH:29]=3)[C:15]=2[CH:14]=1
Reactant: CCCCCCC(CCCCCC)c1ccc(C2c3cc(Br)ccc3Sc3cc4c(cc32)Sc2ccc(Br)cc2C4c2ccc(C(CCCCCC)CCCCCC)cc2)cc1
Agent: O=C1C(Cl)=C(Cl)C(=O)C(Cl)=C1Cl
Solvent: CO
Product: CCCCCCC(CCCCCC)c1ccc(C2=c3cc4c(cc3Sc3ccc(Br)cc32)=C(c2ccc(C(CCCCCC)CCCCCC)cc2)c2cc(Br)ccc2S4)cc1
Temperature: 150 °C
Reaction time: 1 h

Procedure:
A mixture of 7.1 grams of 2,9-Dibromo-7,14-bis-[4-(1-hexyl-heptyl)-phenyl]-7,14-dihydro-5,12-dithia-pentacene and 2.6 grams of chloranil is heated in 100 ml ortho-dichloronezene at 150° C. for 4 hours. After cooling to 22° C., the reaction mixture is poured into 600 ml methanol, filtered off and washed three times with 50 ml methanol. The crude product is suspended in 80 ml acetone, stirred for one hour and filtered off. After drying in vacuum 3.0 grams 2,9-dibromo-7,14-bis-[4-(1-hexyl-heptyl)-phenyl]-5,12-dithia-pentacene are obtained as violet crystals. 1H-NMR(CHCl3): 7.26 (d, 4H, J=8 Hz); 7.04 (d, 4H, J=8 Hz); 6.98 (dd, 2H, J=8.5/2 Hz); 6.71 (d, 2H, J=8.5 Hz); 6.58 (d, 2H, J=2 Hz); 5.86 (s, 2H); 2.57 (m, 2H); 1.8-1.1 (m, 40H); 0.88 (t, 12H).
Reaction SMILES: [C:1]([C:3]1[CH:4]=[C:5]([C:13]2[S:14][C:15]([C:18]3[C:19]([CH2:37][CH3:38])=[C:20]([CH2:24][CH2:25][N:26]4[CH2:31][CH2:30][CH:29]([C:32]([O:34]CC)=[O:33])[CH2:28][CH2:27]4)[CH:21]=[CH:22][CH:23]=3)=[CH:16][N:17]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH:10]([CH3:12])[CH3:11])#[N:2].[OH-].[Na+]>C(O)(C)C.O>[C:1]([C:3]1[CH:4]=[C:5]([C:13]2[S:14][C:15]([C:18]3[C:19]([CH2:37][CH3:38])=[C:20]([CH2:24][CH2:25][N:26]4[CH2:27][CH2:28][CH:29]([C:32]([OH:34])=[O:33])[CH2:30][CH2:31]4)[CH:21]=[CH:22][CH:23]=3)=[CH:16][N:17]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH:10]([CH3:11])[CH3:12])#[N:2]
Reactant: CCOC(=O)C1CCN(CCc2cccc(-c3cnc(-c4ccc(OC(C)C)c(C#N)c4)s3)c2CC)CC1
Agent: [Na+]
Agent: [OH-]
Solvent: CC(C)O
Solvent: O
Product: CCc1c(CCN2CCC(C(=O)O)CC2)cccc1-c1cnc(-c2ccc(OC(C)C)c(C#N)c2)s1
Temperature: 25 °C
Reaction time: 8 h
Yield: 24.8 %

Procedure:
To a solution of ethyl 1-{2-[3-(2-{3-cyano-4-[(1-methylethyl)oxy]phenyl}-1,3-thiazol-5-yl)-2-ethylphenyl]ethyl}-4-piperidinecarboxylate (D86) (204 mg) in isopropanol (40 mL) and water (10 mL) stirred under nitrogen at room temperature was added a solution of NaOH (30.7 mg) in water in one charge. The reaction mixture was stirred at room temperature overnight. Isopropanol was removed in vacuo. The residue was dissolved in water and acidified with 1N HCl to pH=5. The solvent was removed in vacuo, the residue was dissolved in THF, and filtered. The filtrate was purified by Mass Directed AutoPrep to give 1-{2-[3-(2-{3-cyano-4-[(1-methylethyl)oxy]phenyl}-1,3-thiazol-5-yl)-2-ethylphenyl]ethyl}-4-piperidinecarboxylic acid (E37) (48 mg) as a TFA salt (white solid). δH (DMSO-d6, 400 MHz): 1.10 (3H, t), 1.36 (6H, d), 1.76 (2H, m), 2.13 (2H, m), 2.72 (2H, m), 3.07 (4H, m), 3.28 (3H, m), 3.67 (2H, m), 4.91 (1H, m), 7.34 (3H, m), 7.44 (1H, d), 7.85 (1H, s), 8.22 (1H, dd), 8.28 (1H, d), 9.37 (1H, br s), 12.60 (1H, br s). δF (DMSO-d6, 376 MHz): −73.5. MS (ES): C29H33N3O3S requires 503. found 504.1 (M+H+).
Reaction SMILES: [Si]([O:18][CH2:19][CH2:20][CH2:21][C:22]1[CH:49]=[CH:48][C:25]([O:26][CH2:27][CH:28]([O:44][C:45](=[O:47])[CH3:46])[CH2:29][O:30][C:31]2[CH:36]=[CH:35][C:34]([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])=[CH:33][CH:32]=2)=[CH:24][CH:23]=1)(C(C)(C)C)(C1C=CC=CC=1)C1C=CC=CC=1.C(O)(=O)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>O1CCCC1.C(OCC)(=O)C>[OH:18][CH2:19][CH2:20][CH2:21][C:22]1[CH:49]=[CH:48][C:25]([O:26][CH2:27][CH:28]([O:44][C:45](=[O:47])[CH3:46])[CH2:29][O:30][C:31]2[CH:36]=[CH:35][C:34]([C:37]([O:39][C:40]([CH3:41])([CH3:42])[CH3:43])=[O:38])=[CH:33][CH:32]=2)=[CH:24][CH:23]=1
Reactant: CC(=O)OC(COc1ccc(CCCO[Si](c2ccccc2)(c2ccccc2)C(C)(C)C)cc1)COc1ccc(C(=O)OC(C)(C)C)cc1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Solvent: CC(=O)O
Solvent: CCOC(C)=O
Product: CC(=O)OC(COc1ccc(CCCO)cc1)COc1ccc(C(=O)OC(C)(C)C)cc1
Temperature: 70 °C
Yield: 99.2 %

Procedure:
A solution of (2R and 2S)-3-[4-[3-(tert-butyldiphenylsilyloxy)propyl]phenoxy]-1-[4-(tert-butoxycarbonyl)phenoxy]-2-acetoxypropane (7.38 g, 10.8 mmol) in tetrahydrofuran (100 ml) was treated with acetic acid (3.7 ml) and 24 ml (24 mmol) of a 1M solution of tetrabutylammonium fluoride in tetrahydrofuran and the resulting mixture was heated at 70° C. for 4 hours. The cooled mixture was diluted with ethyl acetate, washed with water, saturated sodium bicarbonate, brine and dried (magnesium sulfate). Evaporation of the solvent and chromatography of the residue on silica gel (elution toluene-ethyl acetate, 75:25) gave 4.76 g (97%) of the title alcohol as an oil.
Reaction SMILES: [C:1]1([OH:7])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:8][C:9]1([CH3:28])[CH2:26][C:13]2=[C:14]([C:21]3[CH:25]=[CH:24][NH:23][N:22]=3)[S:15][C:16](S(C)(=O)=O)=[C:12]2[C:11](=[O:27])[CH2:10]1.[OH-].[Na+]>C1COCC1.CCOC(C)=O>[CH3:8][C:9]1([CH3:28])[CH2:26][C:13]2=[C:14]([C:21]3[CH:25]=[CH:24][NH:23][N:22]=3)[S:15][C:16]([O:7][C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)=[C:12]2[C:11](=[O:27])[CH2:10]1
Reactant: Oc1ccccc1
Reactant: CC1(C)CC(=O)c2c(S(C)(=O)=O)sc(-c3cc[nH]n3)c2C1
Agent: [Na+]
Agent: [OH-]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: CC1(C)CC(=O)c2c(Oc3ccccc3)sc(-c3cc[nH]n3)c2C1
Temperature: 25 °C
Yield: 16.7 %

Procedure:
To a solution of phenol (116 mg, 1.1 mmol) in THF (10 mL) was added 6,6-dimethyl-3-methanesulphonyl-1-(pyrazol-3-yl)-4,5,6,7-tetrahydrobenzo[c]thiophen-4-one (0.2 g, 0.62 mmol) and NaOH (0.3 mL of a 4M solution, 1.1 mmol). The mixture was heated at reflux overnight. Phenol (50 mg, 0.62 mmol) and NaOH (0.15 mL of a 4M solution, 0.62 mmol) were then added and the mixture heated at reflux for an additional 8 h. The solution was cooled to room temperature, diluted with EtOAc (100 mL) and washed with NaOH (1M, 2×100 mL). The organic layer was separated, dried (Na2SO4) and evaporated. The residue was chromatographed on silica gel, eluting with hexane:EtOAc (2:1) to give the title compound (35 mg, 18%) as a yellow solid. mp 232-234° C. 1H NMR (360 MHz, CDCl3) δ 1.10 (6H, s), 2.42 (2H, s), 2.86 (2H, s), 6.43 (1H, d, J=2.3 Hz), 7.20-7.26 (3H, m), 7.37 (1H, d, J=7.3 Hz), 7.39 (1H, d, J=8.7 Hz), 7.59 (1H, d, J=2.3 Hz). MS (ES+) 339 (M+1).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([CH:11]=[C:12]([S:14]([F:19])([F:18])([F:17])([F:16])[F:15])[CH:13]=1)[C:5]([N:7]([O:9][CH3:10])[CH3:8])=[O:6].C(=O)([O-])[O-].[Cs+].[Cs+].[I-].[Na+].Br[CH2:29][CH2:30][O:31][CH2:32][CH2:33]Br>CN(C=O)C.CC(=O)OCC>[CH3:10][O:9][N:7]([CH3:8])[C:5](=[O:6])[C:4]1[CH:11]=[C:12]([S:14]([F:19])([F:15])([F:16])([F:17])[F:18])[CH:13]=[C:2]([N:1]2[CH2:33][CH2:32][O:31][CH2:30][CH2:29]2)[CH:3]=1
Reactant: CON(C)C(=O)c1cc(N)cc(S(F)(F)(F)(F)F)c1
Reactant: BrCCOCCBr
Agent: O=C([O-])[O-]
Agent: [Cs+]
Agent: [I-]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CON(C)C(=O)c1cc(N2CCOCC2)cc(S(F)(F)(F)(F)F)c1
Temperature: 130 °C
Yield: 32 %

Procedure:
3-Amino-N-methoxy-N-methyl-5-(pentafluorosulfanyl)benzamide (O5.075; 6.3 g) was dissolved in DMF (80 ml), and cesium carbonate (10.1 g), sodium iodide (0.62 g) and bis(2-bromoethyl) ether (19.37 g) were added. The mixture was divided between 10 microwave vessels, each of which was heated to 130° C. for 3 h. Subsequently, the batches were combined and freed of solvent. The residue was taken up in EA and washed with water. The EA phase was dried and concentrated. The residue was purified using silica gel (120 g cartridge, n-heptane/EA gradient of 0-100% within 30 min). 2.48 g of the title compound were obtained. LC-MS rt: 1.41 min [M+H]+: 377.0 (met. a)