Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([Br:10])[CH:9]=1)[C:5]#[N:6].[C:11]1(B(O)O)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.C([O-])([O-])=O.[K+].[K+]>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.COCCOC>[Br:10][C:8]1[CH:7]=[C:4]([C:5]#[N:6])[CH:3]=[C:2]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH:9]=1
Reactant: N#Cc1cc(Br)cc(Br)c1
Reactant: OB(O)c1ccccc1
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: [K+]
Solvent: COCCOC
Product: N#Cc1cc(Br)cc(-c2ccccc2)c1
Temperature: 95 °C

Procedure:
A mixture of 3,5-dibromobenzonitrile (0.58 g, 2.2 mmol), phenylboronic acid (0.24 g, 2.0 mmol), Pd(PPh3)4 (0.23 g, 0.1 mmol), K2CO3 (3 mL 2 M aqueous solution) and DME (3 mL) was degassed and heated to 95° C. for 12 hr under argon. The reaction mixture was diluted with EtOAc and washed with water. The aqueous layer was extracted with ethyl acetate (2×). The combined organics were dried (MgSO4) and concentrated to give the crude product which was purified with chromatography on silica gel (EtOAc/hexanes) to afford 5-bromobiphenyl-3-carbonitrile.
Reaction SMILES: [C:1]([C:4]1[C:5](=[O:21])[N:6]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[C:7]2[C:12]([C:13]=1O)=[CH:11][CH:10]=[CH:9][N:8]=2)(=O)[CH3:2].O.[NH2:23][NH2:24]>C(O)(=O)C>[CH3:2][C:1]1[C:4]2[C:5](=[O:21])[N:6]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[C:7]3[N:8]=[CH:9][CH:10]=[CH:11][C:12]=3[C:13]=2[NH:24][N:23]=1
Reactant: NN
Reactant: CC(=O)c1c(O)c2cccnc2n(-c2ccccc2)c1=O
Solvent: O
Solvent: CC(=O)O
Product: Cc1n[nH]c2c1c(=O)n(-c1ccccc1)c1ncccc21
Temperature: 25 °C
Yield: 44.3 %

Procedure:
Compound 102 in an amount of 1.2 g (4.3 millimoles) was suspended in 10 ml of glacial acetic acid, and 0.46 ml (9.4 millimoles) of hydrazine monohydrate was added to the suspension. Thereafter, the mixture was heated under reflux for 3 hours. The reaction solution was cooled to room temperature, and the precipitate was collected by filtration and recrystallized from DMF-water to give 530 mg (yield: 44.3%) of Compound 2.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[CH:4][C:5]2[CH2:11][CH2:10][CH2:9][C:8]([C:12]([O:14][CH3:15])=[O:13])=[C:7]([CH3:16])[C:6]=2[CH:17]=1.[F:18][C:19]1[CH:20]=[CH:21][C:22]([C:25](O)=[O:26])=[N:23][CH:24]=1>>[F:18][C:19]1[CH:20]=[CH:21][C:22]([C:25]([NH:1][C:2]2[CH:3]=[CH:4][C:5]3[CH2:11][CH2:10][CH2:9][C:8]([C:12]([O:14][CH3:15])=[O:13])=[C:7]([CH3:16])[C:6]=3[CH:17]=2)=[O:26])=[N:23][CH:24]=1
Reactant: COC(=O)C1=C(C)c2cc(N)ccc2CCC1
Reactant: O=C(O)c1ccc(F)cn1
Product: COC(=O)C1=C(C)c2cc(NC(=O)c3ccc(F)cn3)ccc2CCC1

Procedure:
In a manner similar to the procedure of step 3A, methyl 2-amino-9-methyl-6,7-dihydro-5H-benzo[7]annulene-8-carboxylate from preparation J, step J1, was coupled with 5-fluoropicolinic acid to afford the titled compound of Step 43A. 1H NMR (500 HMz, chloroform-d) δ 9.82 (br. s., 1H), 8.48 (d, J=2.7 Hz, 1H), 8.36 (dd, J=8.7, 4.6 Hz, 1H), 7.73 (d, J=2.3 Hz, 1H), 7.66-7.59 (m, 2H), 7.22 (d, J=8.1 Hz, 1H), 3.83 (s, 3H), 2.57 (t, J=6.6 Hz, 2H), 2.45 (s, 3H), 2.17-2.10 (m, 4H).
Reaction SMILES: CS[C:3](=[N:6][C:7]#[N:8])[S:4][CH3:5].[NH2:9][CH2:10][CH2:11][S:12][CH2:13][C:14]1[C:19]([Br:20])=[CH:18][CH:17]=[CH:16][N:15]=1>>[C:7]([NH:6][C:3](=[N:9][CH2:10][CH2:11][S:12][CH2:13][C:14]1[C:19]([Br:20])=[CH:18][CH:17]=[CH:16][N:15]=1)[S:4][CH3:5])#[N:8]
Reactant: CSC(=NC#N)SC
Reactant: NCCSCc1ncccc1Br
Product: CSC(=NCCSCc1ncccc1Br)NC#N

Procedure:
Reaction of dimethylcyanodithioimidocarbonate with 2-((2-aminoethyl)thiomethyl)-3-bromopyridine by the procedure described in Example 3 (d) gave N-cyano-N'-[2-((3-bromo-2-pyridyl)methylthio)ethyl]-S-methylisothiourea and a mixture of this compound (1.4 g.) and 3-bromo-2-((2-aminoethyl)thiomethyl)pyridine (2.0 g.) was heated at 140° for 6 hours. The product crystallised upon treatment with isopropyl acetate and was recrystallised from aqueous isopropanol to give the title compound (1.1 g.), m.p. 118°-119°.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:20]=[CH:19][C:6]([NH:7][C:8]2[S:9][C:10]3[N:18]=[CH:17][CH:16]=[CH:15][C:11]=3[C:12](=[O:14])[N:13]=2)=[CH:5][CH:4]=1.[H-].[Li+].[CH2:23](Br)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>>[CH2:23]([N:13]1[C:12](=[O:14])[C:11]2[CH:15]=[CH:16][CH:17]=[N:18][C:10]=2[S:9][C:8]1=[N:7][C:6]1[CH:19]=[CH:20][C:3]([O:2][CH3:1])=[CH:4][CH:5]=1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1
Reactant: COc1ccc(Nc2nc(=O)c3cccnc3s2)cc1
Reactant: BrCc1ccccc1
Agent: [H-]
Agent: [Li+]
Product: COc1ccc(N=c2sc3ncccc3c(=O)n2Cc2ccccc2)cc1

Procedure:
The reaction procedure of Example 11 was followed except that 428 mg of 2-(4-methoxyanilino)-4H-pyrido[3,2-e]-1,3-thiazin-4-one, 14 mg of lithium hydride and 0.18 ml of benzyl bromide were used. As a result, 295 mg of 3-benzyl-2-[(4-methoxyphenyl)imino]-2,3-dihydro-4H-pyrido[3,2-e]-1,3-thiazin-4-one was obtained as a low polarity substance, and 174 mg of 2-[N-benzyl-N-(4-methoxyphenyl)amino]-4H-pyrido[3,2-e]-1,3-thiazin-4-one was obtained as a high polarity substance.
Reaction SMILES: [OH-].[Na+].Cl.Cl.[N:5]1[CH:10]=[CH:9][CH:8]=[C:7]([CH2:11][S:12][C:13](=N)N)[N:6]=1.BrC[CH2:18][CH2:19][Cl:20]>O>[Cl:20][CH2:19][CH2:18][CH2:13][S:12][CH2:11][C:7]1[N:6]=[N:5][CH:10]=[CH:9][CH:8]=1
Reactant: ClCCCBr
Reactant: N=C(N)SCc1cccnn1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: ClCCCSCc1cccnn1
Temperature: 75 °C
Reaction time: 15 h
Yield: 67.5 %

Procedure:
A 10 N aqueous solution of sodium hydroxide (84 cc) is added dropwise, in the course of 10 minutes and whilst keeping the temperature below 18° C., to a solution of 2-(pyridazin-3-ylmethyl)-isothiourea dihydrochloride (106 g) in distilled water (220 cc). After heating for 20 minutes at 75° C. and then cooling to 10° C., a 10 N aqueous solution of sodium hydroxide (50 cc) and then 1-bromo-3-chloropropane (69 g) are added, whilst stirring, and stirring is continued for 15 hours at a temperature of about 20° C. The reaction mixture is then extracted three times with methylene chloride (340 cc in total). The organic extracts are combined, washed with distilled water (250 cc) and dried over anhydrous sodium sulphate. After filtration, the solution obtained is poured onto neutral silica gel (80 g) contained in a column of diameter 2.7 cm; the column is then eluted with methylene chloride (700 cc). The first fraction (200 cc) is discarded. The second fraction (500 cc) is collected and concentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at 35° C. Pyridazin-3-ylmethyl 3-chloropropyl sulphide (60 g) is thus obtained in the form of a red oil.
Reaction SMILES: [OH:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][CH:3]=1.[NH2:11][C:12]1[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=1.CCN=C=NCCCN(C)C>CN(C=O)C>[OH:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[O:8])=[CH:9][CH:10]=1
Reactant: O=C(O)c1ccc(O)cc1
Reactant: Nc1ccc(O)cc1
Agent: CCN=C=NCCCN(C)C
Solvent: CN(C)C=O
Product: O=C(Nc1ccc(O)cc1)c1ccc(O)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 34.6 %

Procedure:
4-Hydroxybenzoic acid (1.01 g, 7.31 mmol) and 4-aminophenol (1.19 g, 10.9 mmol) were dissolved in 15 mL of dry DMF. To the above solution EDCI (1.40 g, 7.31 mmoL) was added in one portion and the resulting mixture was stirred at rt overnight under nitrogen. The reaction mixture was then partitioned between EtOAc (200 mL) and water (200 mL). The organic layer was separated, washed consecutively with 1 N HCl, water, saturated sodium bicarbonate solution, water, and brine, and dried over MgSO4. Solvent was removed under reduced pressure and the crude product was purified by column chromatography using EtOAc in hexane as an eluent (10% to 20%) to give 580 mg (34% yield) of 4-hydroxy-N-(4-hydroxyphenyl)-benzamide. MS (ES) m/z: 230.04 (M+1).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][C:11]=1[O:12][CH3:13])[NH:8][C:7](=[O:14])[CH2:6]2.[C:15](OC(=O)C)(=[O:17])[CH3:16]>>[C:15]([N:8]1[C:9]2[C:5](=[CH:4][C:3]([O:2][CH3:1])=[C:11]([O:12][CH3:13])[CH:10]=2)[CH2:6][C:7]1=[O:14])(=[O:17])[CH3:16]
Reactant: COc1cc2c(cc1OC)NC(=O)C2
Reactant: CC(=O)OC(C)=O
Product: COc1cc2c(cc1OC)N(C(C)=O)C(=O)C2
Temperature: 130 °C

Procedure:
16.0 g of 5,6-dimethoxy-2-indolinone (according to Hahn; Tulus; Chem. Ber. 74, 500 (1941)) are dissolved in 170 ml of acetic anhydride and stirred for more than 3 hours at 130° C. After cooling the residue is filtered off, washed with ether and dried in vacuo at 100° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[C:9]([S:13]([CH3:16])(=[O:15])=[O:14])=[N:8][C:7]([CH3:17])=[C:6]2[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.C(Br)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1>>[CH2:16]([S:13]([C:9]1[C:10]2[C:5](=[CH:4][C:3]([O:2][CH3:1])=[CH:12][CH:11]=2)[C:6]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[C:7]([CH3:17])[N:8]=1)(=[O:14])=[O:15])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1
Reactant: BrCc1ccccc1
Reactant: COc1ccc2c(S(C)(=O)=O)nc(C)c(-c3ccccc3)c2c1
Product: COc1ccc2c(S(=O)(=O)Cc3ccccc3)nc(C)c(-c3ccccc3)c2c1

Procedure:
Following the procedure 6-methoxy-3-methyl-1-(methylsulfonyl)-4-phenylisoquinoline, using (in Step B) benzyl bromide in place of iodomethane, the titled compound was synthesized.
Reaction SMILES: [O:1]1[CH:7]2[CH:2]1[C:3]([CH2:17][F:18])([CH2:15][F:16])[O:4][C:5]1[CH:11]=[CH:10][C:9]([N+:12]([O-:14])=[O:13])=[CH:8][C:6]=12.[NH3:19]>C(O)C>[NH2:19][CH:7]1[C:6]2[CH:8]=[C:9]([N+:12]([O-:14])=[O:13])[CH:10]=[CH:11][C:5]=2[O:4][C:3]([CH2:17][F:18])([CH2:15][F:16])[CH:2]1[OH:1]
Reactant: N
Reactant: O=[N+]([O-])c1ccc2c(c1)C1OC1C(CF)(CF)O2
Solvent: CCO
Product: NC1c2cc([N+](=O)[O-])ccc2OC(CF)(CF)C1O
Temperature: 25 °C
Reaction time: 42 h

Procedure:
A mixture of 0.53 g of 3,4-epoxy-2,2-bisfluoromethyl-3,4-dihydro-6-nitro-2H-1-benzopyran, 15 ml of a concentrated aqueous ammonia solution and 15 ml of ethanol was stirred at room temperature for 42 hours. The solvent was distilled off and methylene chloride was added thereto. The mixture was extracted with 1N hydrochloric acid and 2N sodium hydroxide was added to an aqueous layer to form an alkaline solution. The solution was extracted with methylene chloride and the organic layer was washed with water and dried. The solvent was distilled off and the resultant residue was recrystallized from a mixed solvent of ethyl acetate and hexane to obtain 0.32 g of 4-amino-2,2-bisfluoromethyl-3,4-dihydro-6-nitro-2H-1-benzopyran-3-ol represented by the following formula having a melting point of 174-177° C. (decomp.).
Reaction SMILES: O[CH2:2][C:3]1[CH:4]=[CH:5][C:6]([NH:26][C:27](=[O:29])[CH3:28])=[C:7]([C:9]2[C:14]([CH3:15])=[CH:13][C:12]([O:16][CH2:17][C:18]3([OH:24])[CH2:23][CH2:22][S:21][CH2:20][CH2:19]3)=[CH:11][C:10]=2[CH3:25])[CH:8]=1.[F:30][C:31]1[CH:36]=[C:35]([NH:37][S:38]([C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][C:42]=2[N+:47]([O-:49])=[O:48])(=[O:40])=[O:39])[CH:34]=[CH:33][C:32]=1[CH2:50][CH2:51][C:52]([O:54][CH2:55][CH3:56])=[O:53].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>O1CCCC1>[C:27]([NH:26][C:6]1[C:7]([C:9]2[C:10]([CH3:25])=[CH:11][C:12]([O:16][CH2:17][C:18]3([OH:24])[CH2:23][CH2:22][S:21][CH2:20][CH2:19]3)=[CH:13][C:14]=2[CH3:15])=[CH:8][C:3]([CH2:2][N:37]([S:38]([C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][C:42]=2[N+:47]([O-:49])=[O:48])(=[O:39])=[O:40])[C:35]2[CH:34]=[CH:33][C:32]([CH2:50][CH2:51][C:52]([O:54][CH2:55][CH3:56])=[O:53])=[C:31]([F:30])[CH:36]=2)=[CH:4][CH:5]=1)(=[O:29])[CH3:28]
Reactant: CC(=O)Nc1ccc(CO)cc1-c1c(C)cc(OCC2(O)CCSCC2)cc1C
Reactant: CCOC(=O)CCc1ccc(NS(=O)(=O)c2ccccc2[N+](=O)[O-])cc1F
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: CCOC(=O)CCc1ccc(N(Cc2ccc(NC(C)=O)c(-c3c(C)cc(OCC4(O)CCSCC4)cc3C)c2)S(=O)(=O)c2ccccc2[N+](=O)[O-])cc1F
Temperature: 25 °C
Yield: 91.7 %

Procedure:
To a solution of N-{5-(hydroxymethyl)-4′-[(4-hydroxytetrahydro-2H-thiopyran-4-yl)methoxy]-2′,6′-dimethylbiphenyl-2-yl}acetamide (148 mg, 0.36 mmol), ethyl 3-(2-fluoro-4-{[(2-nitrophenyl)sulfonyl]amino}phenyl)propanoate (157 mg, 0.40 mmol) and triphenylphosphine (189 mg, 0.72 mmol) in tetrahydrofuran (4 mL) was added diethyl azodicarboxylate (40% toluene solution, 0.33 mL, 0.72 mmol) under stirring at room temperature, and the mixture was stirred for one day. The reaction mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (hexane/ethyl acetate=9/1-hexane/ethyl acetate=1/3) to give the title compound (262 mg, yield 83%) as a colorless amorphous powder.
Reaction SMILES: [CH:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]2[C:14]3[C:15]([CH3:20])=[CH:16][CH:17]=[C:18]([CH3:19])[C:13]=3[O:12][C:11]2=[O:21])=[CH:6][CH:5]=1)([CH3:3])[CH3:2]>CCCCCC.C(OCC)(=O)C>[OH:21][CH2:11][CH:10]([C:14]1[C:15]([CH3:20])=[CH:16][CH:17]=[C:18]([CH3:19])[C:13]=1[OH:12])[C:7]1[CH:6]=[CH:5][C:4]([CH:1]([CH3:3])[CH3:2])=[CH:9][CH:8]=1
Reactant: Cc1ccc(C)c2c1OC(=O)C2c1ccc(C(C)C)cc1
Solvent: CCCCCC
Solvent: CCOC(C)=O
Product: Cc1ccc(C)c(C(CO)c2ccc(C(C)C)cc2)c1O
Yield: 88 %

Procedure:
Using 3-(4-isopropylphenyl)-4,7-dimethyl-1-benzofuran-2(3H)-one synthesized in Reference Example 230, the title compound was synthesized in the same manner as in Reference Example 8. Yield 88%. Melting point: 88-89° C. (hexane-ethyl acetate).
Reaction SMILES: [Cl:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([O:10][C:11]2[CH:19]=[CH:18][CH:17]=[C:16]3[C:12]=2[CH2:13][CH2:14][C:15]3=O)[CH:3]=1.CN.[C:23]([BH3-])#[N:24].[Na+].[C:27]([OH:34])(=[O:33])/[CH:28]=[CH:29]/[C:30]([OH:32])=[O:31]>CO.C(O)(=O)C>[C:27]([OH:34])(=[O:33])/[CH:28]=[CH:29]/[C:30]([OH:32])=[O:31].[Cl:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([O:10][C:11]2[CH:19]=[CH:18][CH:17]=[C:16]3[C:12]=2[CH2:13][CH2:14][CH:15]3[NH:24][CH3:23])[CH:3]=1
Reactant: N#Cc1ccc(Cl)cc1Oc1cccc2c1CCC2=O
Reactant: [BH3-]C#N
Agent: CN
Agent: O=C(O)/C=C/C(=O)O
Agent: [Na+]
Solvent: CO
Solvent: CC(=O)O
Product: CNC1CCc2c(Oc3cc(Cl)ccc3C#N)cccc21
Yield: 78.7 %

Procedure:
4-Chloro-2-(1-oxoindan-4-yloxy)benzonitrile (0.12 g, 0.42 mmol), methylamine (33% in ethanol, 1.0 mL, 8.0 mmol) and sodium cyanoborohydride (100 mg, 0.86 mmol) were stirred at ambient temperature in a solution of glacial acetic acid (1.0 mL) in methanol (30 mL) for 5 days. The solvent was removed in vacuo. The residue was treated with 10% sodium carbonate solution and extracted with ethyl acetate. The ethyl acetate layer was separated and fumaric acid (40 mg, 0.34 mmol) was added. After the solvent was removed in vacuo, the residue was triturated with ethyl acetate overnight, collected by filtration, and dried to give 4-chloro-2-(1-methylaminoindan-4-yloxy)benzonitrile fumarate (111 mg, 63%) as a white solid.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:26]=[CH:25][C:6]([CH2:7][O:8][CH2:9][C@H:10]([CH3:24])[C@H:11]([O:16][Si:17]([C:20]([CH3:23])([CH3:22])[CH3:21])([CH3:19])[CH3:18])[C@@H:12]([CH3:15])[CH2:13]O)=[CH:5][CH:4]=1.CCN(CC)CC.[H-].[Na+].[CH3:36][CH2:37][O:38][C:39]([CH3:41])=[O:40].CCCCCC>>[CH2:37]([O:38][C:39](=[O:40])/[CH:41]=[CH:13]/[C@H:12]([CH3:15])[C@@H:11]([O:16][Si:17]([C:20]([CH3:22])([CH3:21])[CH3:23])([CH3:19])[CH3:18])[C@@H:10]([CH3:24])[CH2:9][O:8][CH2:7][C:6]1[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:26][CH:25]=1)[CH3:36]
Reactant: CCOC(C)=O
Reactant: COc1ccc(COC[C@H](C)[C@H](O[Si](C)(C)C(C)(C)C)[C@@H](C)CO)cc1
Agent: [H-]
Agent: [Na+]
Solvent: CCN(CC)CC
Solvent: CCCCCC
Product: CCOC(=O)/C=C/[C@H](C)[C@@H](O[Si](C)(C)C(C)(C)C)[C@@H](C)COCc1ccc(OC)cc1
Yield: 63 %

Procedure:
The procedure for 10 was used with the aldehyde from 21 (17.5 g, 31.6 mmol), Py.SO3 (15.2 g, 95.5 mmol) and Et3N (13.3 mL, 95.5 mmol), NaH (0.90 g, 39.7 mmol) and triethylphosphonoacetate (7.2 mL, 40.3 mmol) to yield 8.96 g (63% for 3 steps) of the ester 22 by flash column chromatography (EtOAc/Hexane 1:9) as a colorless oil: IR (CHCl3) 2957, 2931, 2856, 1720, 1651, 1613, 1513, 1463, 1366, 1250, 1180, 1093, 1077, 837 cm−1; 1H NMR (300 MHz, CDCl3) ε7.31-7.27 (m, 2H), 7.03 (dd, J=15.8, 7.8 Hz, 1H), 6.93-6.91 (m, 2H), 5.83 (dd, J=15.8, 1.3 Hz, 1H), 4.48b -4.40 (m, 2H), 4.23 (q, J=7.1 Hz, 2H), 3.84 (s, 3H), 3.67 (m, 1H), 3.52 (m, 1H), 3.30 (dd, J=9.1, 7.2 Hz, 1H), 2.59 (m, 1H), 2.00 (m, 1H), 1.33 (t, J=7.1 Hz, 3H), 1.09 (d, J=6.8 Hz, 3H), 1.01 (d, J=7.0 Hz, 3H), 0.94 (s, 9H), 0.08 (m, 6H); 13C NMR (75 MHz, CDCl3) δ 166.5, 159.0, 152.7, 130.6, 129.0, 120.4, 113.6, 76.8, 72.5, 71.8, 60.0, 55.1, 40.2, 38.0, 26.0, 18.2, 14.8, 14.3, 14.2, −4.0, −4.2; LRMS (ESI) 473.2 [M+Na]+; HRMS (ESI) calcd for C25H42O5SiNa 473.2699 [M+Na]+, found 473.2716; [α]20D−28.3 (c 0.41, CHCl3).
Reaction SMILES: C1(S([N:10]2[C:14]3=[N:15][CH:16]=[C:17]([O:19][CH2:20][CH2:21][O:22][CH3:23])[CH:18]=[C:13]3[CH:12]=[C:11]2[C:24]([C:31]2[CH:36]=[CH:35][C:34]([S:37]([CH3:40])(=[O:39])=[O:38])=[CH:33][CH:32]=2)=[CH:25][CH:26]2[CH2:30][CH2:29][CH2:28][CH2:27]2)(=O)=O)C=CC=CC=1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>O1CCCC1.C(OCC)(=O)C>[CH:26]1([CH:25]=[C:24]([C:11]2[NH:10][C:14]3=[N:15][CH:16]=[C:17]([O:19][CH2:20][CH2:21][O:22][CH3:23])[CH:18]=[C:13]3[CH:12]=2)[C:31]2[CH:36]=[CH:35][C:34]([S:37]([CH3:40])(=[O:39])=[O:38])=[CH:33][CH:32]=2)[CH2:30][CH2:29][CH2:28][CH2:27]1
Reactant: COCCOc1cnc2c(c1)cc(C(=CC1CCCC1)c1ccc(S(C)(=O)=O)cc1)n2S(=O)(=O)c1ccccc1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: COCCOc1cnc2[nH]c(C(=CC3CCCC3)c3ccc(S(C)(=O)=O)cc3)cc2c1
Yield: 100 %

Procedure:
A solution of 1-benzenesulfonyl-2-[2-cyclopentyl-1-(4-methanesulfonyl-phenyl)-vinyl]-5-(2-methoxy-ethoxy)-1H-pyrrolo[2,3-b]pyridine (343 mg, 0.59 mmol) in tetrahydrofuran (0.5 mL) and a tetrabutylammonium fluoride solution in tetrahydrofuran (1 M, 4 mL, 4 mmol) was stirred at room temperature for 12 h. The mixture was diluted with ethyl acetate (150 mL), and washed with a saturated aqueous ammonium chloride solution, brine, dried over anhydrous sodium sulfate and concentrated in vacuo to afford 2-[2-cyclopentyl-1-(4-methanesulfonyl-phenyl)-vinyl]-5-(2-methoxy-ethoxy)-1H-pyrrolo[2,3-b]pyridine (260 mg, quant.) as a white solid: LC/MS m/e calcd for C24H28N2O4S [M+H]+ 441.57, observed 441.2.
Reaction SMILES: [C:1]([C:4]1[CH:26]=[CH:25][C:7]([O:8][CH2:9][CH2:10][CH2:11][S:12]([C:15]2[CH:20]=[CH:19][C:18]([C:21]([O:23]C)=[O:22])=[CH:17][N:16]=2)(=[O:14])=[O:13])=[C:6]([CH2:27][CH2:28][CH3:29])[C:5]=1[OH:30])(=[O:3])[CH3:2].[OH-].[Na+].O>C1COCC1>[C:1]([C:4]1[CH:26]=[CH:25][C:7]([O:8][CH2:9][CH2:10][CH2:11][S:12]([C:15]2[CH:20]=[CH:19][C:18]([C:21]([OH:23])=[O:22])=[CH:17][N:16]=2)(=[O:14])=[O:13])=[C:6]([CH2:27][CH2:28][CH3:29])[C:5]=1[OH:30])(=[O:3])[CH3:2]
Reactant: CCCc1c(OCCCS(=O)(=O)c2ccc(C(=O)OC)cn2)ccc(C(C)=O)c1O
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Product: CCCc1c(OCCCS(=O)(=O)c2ccc(C(=O)O)cn2)ccc(C(C)=O)c1O
Temperature: 25 °C
Reaction time: 8 h

Procedure:
The compound of Example 3, (570 mg, 1.31 mmoles) was dissolved in THF (6 ml) to which was added 1N NaOH (3 ml) and H2O (3 ml). The reaction mixture was stirred at room temperature under N2 overnight. The THF was removed in vacuo. The aqueous phase was washed with CHCl3. Then the aqueous phase was acidified with concentrated HCl until slightly acid (pH about 5-6). The resulting beige solid was filtered, taken up in CHCl3 (about 500 ml), and the organic solvent was dried and concentrated. The residue was triturated with ether and filtered to afford the title compound, m.p. 177°-179°.
Reaction SMILES: [CH3:1][O:2][C:3]1[C:8](I)=[CH:7][C:6]([C:10](=[O:26])[NH:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[CH:5][C:4]=1I.[CH:28]([C:30]1[CH:31]=[C:32](B(O)O)[CH:33]=[CH:34][CH:35]=1)=[O:29]>>[CH:28]([C:30]1[CH:31]=[C:32]([C:4]2[CH:5]=[C:6]([C:10](=[O:26])[NH:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[CH:7]=[C:8]([C:4]3[CH:3]=[CH:8][CH:7]=[C:6]([CH:10]=[O:26])[CH:5]=3)[C:3]=2[O:2][CH3:1])[CH:33]=[CH:34][CH:35]=1)=[O:29]
Reactant: O=Cc1cccc(B(O)O)c1
Reactant: COc1c(I)cc(C(=O)NCCCCCCCCc2ccccc2)cc1I
Product: COc1c(-c2cccc(C=O)c2)cc(C(=O)NCCCCCCCCc2ccccc2)cc1-c1cccc(C=O)c1

Procedure:
The title compound was prepared as a solid (0.479 g, 75%) from 2,6-diiodo-4-(8-phenyl-octylcarbamoyl)phenyl methyl ether using 3-formylbenzeneboronic acid and a procedure similar to step 3 of Example 93; 1H NMR (DMSO-d6) δ 1.21-1.35 (m, 8H), 1.46-1.60 (m, 4H), 2.47-2.58 (m, 2H), 3.13 (s, 3H), 3.21-3.32 (m, 2H), 7.09-7.19 (m, 3H), 7.21-7.30 (m, 2H), 7.54 (t, J=7.5 Hz, 2H), 7.94-8.03 (m, 6H), 8.17 (s, 2H), 8.61 (t, J=5.6 Hz, 1H), 10.14 (s, 2H); mass spectrum [(+) ESI], m/z 548 (M+H)+, 570 (M+Na)+.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1F)[O:8][CH:7](C1C=CC=CC=1)[CH2:6][C:5]2=O.[C:20](=[N:26][Si](C)(C)C)=[N:21][Si](C)(C)C>C(Cl)Cl.Cl[Ti](Cl)(Cl)Cl>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[O:8][CH2:7][CH2:6][C:5]2=[N:26][C:20]#[N:21]
Reactant: C[Si](C)(C)N=C=N[Si](C)(C)C
Reactant: O=C1CC(c2ccccc2)Oc2cc(F)c(Br)cc21
Agent: Cl[Ti](Cl)(Cl)Cl
Solvent: ClCCl
Product: N#CN=C1CCOc2ccc(Br)cc21
Temperature: 0 °C
Reaction time: 1 h
Yield: 93.3 %

Procedure:
To a solution of 6-bromo-7-fluoro-2-phenylchroman-4-one (289.3 mg, 1.28 mmol) in DCM (10 mL) was added TiCl4 (2.6 mL, 1 M in CH2Cl2) dropwise within 15 minutes at room temperature. After stirring for 1 h, N,N′-methanediylidenebis(1,1,1-trimethylsilanamine) (0.63 mL, 2.82 mmol) was added dropwise. The mixture was stirred at room temperature overnight and poured into ice-water (50 g). The organic layer was separated and the aqueous layer was extracted with CH2Cl2. The combined organic layer was dried and concentrated to give crude N-(6-bromochroman-4-ylidene)cyanamide (300 mg, 94%).
Reaction SMILES: ClC1C=CC=C(C(OO)=[O:9])C=1.[S:12]([NH:16][C:17](=[NH:22])[CH2:18][CH2:19][S:20][CH3:21])(=[O:15])(=[O:14])[NH2:13]>C(Cl)(Cl)Cl.CO>[S:12]([NH:16][C:17](=[NH:22])[CH2:18][CH2:19][S:20]([CH3:21])=[O:9])(=[O:14])(=[O:15])[NH2:13]
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: CSCCC(=N)NS(N)(=O)=O
Solvent: ClC(Cl)Cl
Solvent: CO
Product: CS(=O)CCC(=N)NS(N)(=O)=O
Reaction time: 2 h

Procedure:
A solution of commercial 80% pure m-chloroperbenzoic acid (5.4 g, 25 mmol) in chloroform (40 ml) was added dropwise to a solution of N-sulfamyl-3-(methylthio)propionamidine (4.94 g, 25 mmol) in methanol (50 ml) at room temperature. After stirring for two hours, the product was collected by filtration, analytically pure, to give 4.44 g, mp 141°-144°.