Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][CH:3]([O:14][CH3:15])[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH:12]=[CH2:13].[CH2:16]([O:18][SiH:19]([O:23][CH2:24][CH3:25])[O:20][CH2:21][CH3:22])[CH3:17]>>[CH3:15][O:14][CH:3]([O:2][CH3:1])[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][Si:19]([O:23][CH2:24][CH3:25])([O:20][CH2:21][CH3:22])[O:18][CH2:16][CH3:17]
Reactant: CCO[SiH](OCC)OCC
Reactant: C=CCCCCCCCCC(OC)OC
Product: CCO[Si](CCCCCCCCCCC(OC)OC)(OCC)OCC
Temperature: 25 °C
Reaction time: 3 h
Yield: 65.2 %

Procedure:
36.39 g of 11,11-dimethoxyundec-1-ene (7) obtained above in the first stage (170 mmol) are dissolved in 31.025 g of 97% triethoxysilane (34.86 ml, 183 mmol, 1.08 eq.). Subsequently, 0.424 g (0.45 mmol, 0.0026 eq.) of Karstedt catalyst is added very slowly. After stirring at ambient temperature for 3 hours, the crude reaction product is purified by distillation to give 41.88 g of a colorless liquid (yield of 65%) melting at a temperature of 115°-120° C. (at a pressure of 10−2 mm of mercury).
Reaction SMILES: [Br:1][CH2:2][CH2:3][C:4]1[CH:11]=[CH:10][CH:9]=[CH:8][C:5]=1[CH2:6]Br.[CH2:12]([O:14][P:15]([O:19]CC)[O:16][CH2:17][CH3:18])[CH3:13]>>[Br:1][CH2:2][CH2:3][C:4]1[CH:11]=[CH:10][CH:9]=[CH:8][C:5]=1[CH2:6][P:15](=[O:19])([O:16][CH2:17][CH3:18])[O:14][CH2:12][CH3:13]
Reactant: CCOP(OCC)OCC
Reactant: BrCCc1ccccc1CBr
Product: CCOP(=O)(Cc1ccccc1CCBr)OCC
Yield: 69.1 %

Procedure:
In a round bottom flask equipped for distillation, 15.0 g (54 mmol) of 2-(2-bromoethyl)benzyl bromide and 9.0 g (54 mmol) of triethylphosphite were heated on an oil bath with stirring at 90°-100° C. When ethyl bromide ceased distilling off (1 h) the remaining volatile by-products and triethylphosphite were removed from the mixture by distillation under vacuum. The viscous oil which remained was chromatographed on a column of silica gel with hexane-ethyl acetate (1:1) as eluant. The combined fractions were concentrated under reduced pressure to yield 12.5 g (70%) of the product as a yellow oil. IR(neat): 2987, 1249, 1170, 1064, 964, 802 cm-1. 1H NMR(CDCl3) δ 1.2 (t, 6H); 3.0-4.35 (m, 10H); 7.2 (s, 4H).
Reaction SMILES: [F:1][C:2]([F:12])([F:11])[S:3][C:4]1[CH:9]=[CH:8][C:7](Br)=[CH:6][CH:5]=1.[CH2:13]1[CH2:17]O[CH2:15][CH2:14]1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:1][C:2]([F:12])([F:11])[S:3][C:4]1[CH:9]=[CH:8][C:7]([C:15]#[C:14][C:13]2[CH:17]=[CH:9][C:4]([S:3][C:2]([F:12])([F:11])[F:1])=[CH:5][CH:6]=2)=[CH:6][CH:5]=1
Reactant: C1CCOC1
Reactant: FC(F)(F)Sc1ccc(Br)cc1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Product: FC(F)(F)Sc1ccc(C#Cc2ccc(SC(F)(F)F)cc2)cc1
Yield: 80 %

Procedure:
A mixture of 4-(trifluoromethylthio)bromobenzene (0.47 g, 1.82 mmol), bis (tri-N-butylstannyl)acetylene (0.5 g, 0.83 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.05 g, 0.04 mmol) in THF (10 mL) under nitrogen was heated to reflux overnight. After the usual work-up, it was purified by column chromatography to give 0.24 g (80%) of 1,2-bis(4-trifluoromethylthiophenyl)acetylene as a white fluffy solid. 1HNMR (360 MHz, DMSO-d6) δ7.72-7.79 (m, 8H). MS-EI m/z 378 [M+].
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[Sn](CCCC)(CCCC)CCCC.[CH2:20]([O:24][C:25]([N:27]([C:44]1[C:49]([O:50][CH3:51])=[N:48][C:47]([CH3:52])=[CH:46][N:45]=1)[S:28]([C:31]1[C:32]([C:37]2[CH:42]=[CH:41][C:40](I)=[CH:39][CH:38]=2)=[N:33][CH:34]=[CH:35][CH:36]=1)(=[O:30])=[O:29])=[O:26])[CH:21]([CH3:23])[CH3:22].O>C1(C)C(C)=CC=CC=1.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>[CH2:20]([O:24][C:25]([N:27]([C:44]1[C:49]([O:50][CH3:51])=[N:48][C:47]([CH3:52])=[CH:46][N:45]=1)[S:28]([C:31]1[C:32]([C:37]2[CH:42]=[CH:41][C:40]([C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=3)=[CH:39][CH:38]=2)=[N:33][CH:34]=[CH:35][CH:36]=1)(=[O:30])=[O:29])=[O:26])[CH:21]([CH3:23])[CH3:22]
Reactant: CCCC[Sn](CCCC)(CCCC)c1ccccn1
Reactant: COc1nc(C)cnc1N(C(=O)OCC(C)C)S(=O)(=O)c1cccnc1-c1ccc(I)cc1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: Cc1ccccc1C
Solvent: O
Product: COc1nc(C)cnc1N(C(=O)OCC(C)C)S(=O)(=O)c1cccnc1-c1ccc(-c2ccccn2)cc1
Temperature: 125 °C
Yield: 31.7 %

Procedure:
Tetrakis(triphenylphosphine)palladium (0) (45 mg) was added to a deoxygenated solution of (2-pyridyl)tributylstannane (294 mg) and N-isobutoxycarbonyl-N-(3-methoxy-5-methylpyrazin-2-yl)-2-(4-iodophenyl)pyridine-3-sulphonamide(465 mg) in xylene (15 ml). The mixture was stirred and heated under argon at 125° C. for 17 hours and then allowed to cool to ambient temperature. Water was added and the mixture was extracted with ethyl acetate. The organic layers were combined, washed with saturated sodium chloride solution then dried (MgSO4). Volatile material was removed by evaporation and the residue was purified by chromatography on a silica gel Mega Bond Elut column, eluting with 0-65% ethyl acetate/hexane to give N-isobutoxycarbonyl-N-(3-methoxy-5-methylpyrazin-2-yl)-2-(4-(2-pyridyl)phenyl)pyridine-3-sulphonamide (135 mg) as a foam; 1H NMR (CDCl3): 0.7 (d, 6H), 1.7 (m, 1H), 2.5 (s, 3H), 3.8 (d, 2H), 4.0 (s, 3H), 7.5 (dd, 2H), 7.6-7.8 (m, 4H), 7.9 (s, 1H), 8.1 (dd, 2H), 8.7 (dd, 1H), 8.9 (dd, 1H), 9.0 (dd, 1H); mass spectrum (+ve ESP): 534 (M+H)+.
Reaction SMILES: [CH2:1]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([NH:17][C:18]3[C:27]4[C:22](=[CH:23][CH:24]=[C:25](Br)[CH:26]=4)[N:21]=[CH:20][N:19]=3)=[CH:14][CH:15]=2)[CH:10]=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([Sn](CCCC)(CCCC)[C:34]1[O:35][C:36]([CH:39]2[O:43][CH2:42][CH2:41][O:40]2)=[CH:37][CH:38]=1)CCC>O1CCOCC1>[CH2:1]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([NH:17][C:18]3[C:27]4[C:22](=[CH:23][CH:24]=[C:25]([C:34]5[O:35][C:36]([CH:39]6[O:43][CH2:42][CH2:41][O:40]6)=[CH:37][CH:38]=5)[CH:26]=4)[N:21]=[CH:20][N:19]=3)=[CH:14][CH:15]=2)[CH:10]=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CCCC[Sn](CCCC)(CCCC)c1ccc(C2OCCO2)o1
Reactant: Brc1ccc2ncnc(Nc3ccc4c(cnn4Cc4ccccc4)c3)c2c1
Solvent: C1COCCO1
Product: c1ccc(Cn2ncc3cc(Nc4ncnc5ccc(-c6ccc(C7OCCO7)o6)cc45)ccc32)cc1

Procedure:
Prepared according to Procedure B from (1-benzyl-1H-indazol-5-yl)-(6-bromoquinazolin-4-yl)-amine (4.3 g), 2-(tributylstannyl)-5-(1,3-dioxolan-2-yl)-furan (J. Chem. Soc., Chem Commun., (1988), 560) (10 g) and 1,4-bis(diphenylphosphino)palladium(II)chloride (1 g) in dioxane. The solvent was removed in vacuo and the residue chromatographed on silica. Subsequent trituration gave the title compound δH [2H6]-DMSO 10.13 (1H, s), 8.85 (1H, s), 8.54 (1H, s), 8.20 (3H, m), 7.80 (3H, m), 7.30 (5H, m), 7.13 (1H, d), 6.79 (1H, d), 6.04 (1H, s), 5.71 (2H, s), 4.15 (4H, m).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([C:8]#[C:9][C:10]2[CH:23]=[CH:22][N:13]3[C:14](=[O:21])[C:15]([C:18](O)=[O:19])=[CH:16][N:17]=[C:12]3[CH:11]=2)[CH:5]=[CH:6][CH:7]=1.C(Cl)(=O)C([Cl:27])=O>CN(C=O)C.ClCCl>[F:1][C:2]1[CH:3]=[C:4]([C:8]#[C:9][C:10]2[CH:23]=[CH:22][N:13]3[C:14](=[O:21])[C:15]([C:18]([Cl:27])=[O:19])=[CH:16][N:17]=[C:12]3[CH:11]=2)[CH:5]=[CH:6][CH:7]=1
Reactant: O=C(O)c1cnc2cc(C#Cc3cccc(F)c3)ccn2c1=O
Reactant: O=C(Cl)C(=O)Cl
Solvent: CN(C)C=O
Solvent: ClCCl
Product: O=C(Cl)c1cnc2cc(C#Cc3cccc(F)c3)ccn2c1=O
Temperature: 25 °C
Reaction time: 3 h

Procedure:
To a mixture of 8-((3-fluorophenyl)ethynyl)-4-oxo-4H-pyrido[1,2-a]pyrimidine-3-carboxylic acid (50 mg, 0.162 mmol, 1 equiv) and 1 drop DMF in dichloromethane was added oxalyl dichloride (1 mL) dropwise. The reaction mixture was stirred at room temperature for 3 h and concentrated to give the desired product, which was directly used for the next step.
Reaction SMILES: Br[C:2]1[C:3]([F:19])=[CH:4][C:5]2[O:11][CH2:10][CH2:9][N:8]3[CH:12]=[C:13]([C:15]([NH2:17])=[O:16])[N:14]=[C:7]3[C:6]=2[CH:18]=1.[Cl:20][C:21]1[CH:22]=[CH:23][C:24]([C:27]([OH:31])([C:29]#[CH:30])[CH3:28])=[N:25][CH:26]=1>>[Cl:20][C:21]1[CH:22]=[CH:23][C:24]([C:27]([OH:31])([CH3:28])[C:29]#[C:30][C:2]2[C:3]([F:19])=[CH:4][C:5]3[O:11][CH2:10][CH2:9][N:8]4[CH:12]=[C:13]([C:15]([NH2:17])=[O:16])[N:14]=[C:7]4[C:6]=3[CH:18]=2)=[N:25][CH:26]=1
Reactant: C#CC(C)(O)c1ccc(Cl)cn1
Reactant: NC(=O)c1cn2c(n1)-c1cc(Br)c(F)cc1OCC2
Product: CC(O)(C#Cc1cc2c(cc1F)OCCn1cc(C(N)=O)nc1-2)c1ccc(Cl)cn1
Yield: 28 %

Procedure:
Similar to as described in General Procedure G, 10-bromo-9-fluoro-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-2-carboxamide was reacted with 2-(5-chloropyridin-2-yl)but-3-yn-2-ol to give the titled compound as a grey solid (60 mg, 28%).
Reaction SMILES: FC(F)(F)C1C=CC(C[O:8][C:9](=[O:29])[C:10]2[CH:15]=[CH:14][C:13]([O:16][CH2:17][C:18]3[CH:23]=[CH:22][C:21]([C:24]([F:27])([F:26])[F:25])=[CH:20][CH:19]=3)=[C:12](F)[CH:11]=2)=CC=1.[F:34]C(F)(F)C1C=CC(COC(=O)C2C=CC(OCC3C=CC(F)=CC=3)=C(F)C=2)=CC=1>>[F:34][C:11]1[CH:12]=[C:13]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][C:21]([C:24]([F:27])([F:26])[F:25])=[CH:20][CH:19]=2)[CH:14]=[CH:15][C:10]=1[C:9]([OH:8])=[O:29]
Reactant: O=C(OCc1ccc(C(F)(F)F)cc1)c1ccc(OCc2ccc(C(F)(F)F)cc2)c(F)c1
Reactant: O=C(OCc1ccc(C(F)(F)F)cc1)c1ccc(OCc2ccc(F)cc2)c(F)c1
Product: O=C(O)c1ccc(OCc2ccc(C(F)(F)F)cc2)cc1F
Yield: 90 %

Procedure:
As described for example 18b, 3-fluoro-4-(4-trifluoromethyl-benzyloxy)-benzoic acid 4-trifluoromethyl-benzyl ester (5.3 g, 11 mmol) [instead of 3-fluoro-4-(4-fluoro-benzyloxy)-benzoic acid 4-trifluoromethyl-benzyl ester] was converted to the title compound (3.1 g, 90%) which was obtained as a white solid. MS: m/e=312.9 (M−H−).
Reaction SMILES: [C:1]([N:4]1[C:22](=[O:23])[NH:21][C:20](=[O:24])[C@@:5]21[O:9][C@@H:8]([CH2:10]I)[C@H:7]([O:12][C:13](=[O:15])[CH3:14])[C@H:6]2[O:16][C:17](=[O:19])[CH3:18])(=[O:3])[CH3:2].[C:25]([O-:28])(=[S:27])[CH3:26].C[N+](C)(C)C>COCCOC.ClCCl>[C:1]([N:4]1[C:22](=[O:23])[NH:21][C:20](=[O:24])[C@@:5]21[O:9][C@@H:8]([CH2:10][S:27][C:25](=[O:28])[CH3:26])[C@H:7]([O:12][C:13](=[O:15])[CH3:14])[C@H:6]2[O:16][C:17](=[O:19])[CH3:18])(=[O:3])[CH3:2]
Reactant: CC([O-])=S
Reactant: CC(=O)O[C@H]1[C@H](CI)O[C@]2(C(=O)NC(=O)N2C(C)=O)[C@@H]1OC(C)=O
Agent: C[N+](C)(C)C
Solvent: COCCOC
Solvent: ClCCl
Product: CC(=O)O[C@H]1[C@H](CSC(C)=O)O[C@]2(C(=O)NC(=O)N2C(C)=O)[C@@H]1OC(C)=O
Temperature: 45 °C
Yield: 94.4 %

Procedure:
To a solution of (2R, 3R, 4R, 5S)-6-acetyl-2-iodomethyl-3, 4-diacetoxy-1-oxa-6,8-diazaspiro (4,4) nonane-7, 9-dione (598 mg, 1.32 mm) in anhydrous DME (10 ml) is added, under N2, tetramethylammonium thioacetate (353 mg, 2.37 mm) in one portion. The resulting mixture is heated at 45° C. for 4 hours, then diluted with dichloromethane and washed with brine, dried, and evaporated for dryness. The crude product is purified by thin-layer chromatography to give (2R, 3R, 4R, 5S)-6-acetyl-2-acetylthiomethyl-3, 4-diacetoxy-1-oxa-6, 8-diazaspiro (4,4) nonane-7, 9-dione (500 mg) as a hygroscopic foam.
Reaction SMILES: [C:1]([NH:8][C@@H:9]([C:17]([OH:19])=O)[CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[NH2:20][C@H:21]1[N:27]=[C:26]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=2[F:34])[C:25]2[CH:35]=[CH:36][CH:37]=[CH:38][C:24]=2[N:23]([CH3:39])[C:22]1=[O:40].C1(N=C=NC2CCCCC2)CCCCC1>>[CH3:7][C:4]([O:3][C:1](=[O:2])[NH:8][CH:9]([CH2:10][C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1)[C:17]([NH:20][CH:21]1[N:27]=[C:26]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=2[F:34])[C:25]2[CH:35]=[CH:36][CH:37]=[CH:38][C:24]=2[N:23]([CH3:39])[C:22]1=[O:40])=[O:19])([CH3:5])[CH3:6]
Reactant: CC(C)(C)OC(=O)N[C@H](Cc1ccccc1)C(=O)O
Reactant: CN1C(=O)[C@@H](N)N=C(c2ccccc2F)c2ccccc21
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Product: CN1C(=O)C(NC(=O)C(Cc2ccccc2)NC(=O)OC(C)(C)C)N=C(c2ccccc2F)c2ccccc21

Procedure:
The procedure of Example 77 was carried out in which Boc-D-phenylalanine was coupled to 3(S)-(-)-amino-1,3-dihydro-1-methyl-5-(2-fluorophenyl)-2H-1,4-benzodiazepin-2-one with dicyclohexylcarbodiimide. Following the identical work-up and purification procedure of Example 77 gave the analytical product.
Reaction SMILES: [CH3:1][N:2]([CH3:15])[CH2:3][CH2:4][CH2:5][O:6][C:7]1[CH:14]=[CH:13][CH:12]=[CH:11][C:8]=1[CH:9]=O.[NH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>C(O)C>[CH3:1][N:2]([CH3:15])[CH2:3][CH2:4][CH2:5][O:6][C:7]1[CH:14]=[CH:13][CH:12]=[CH:11][C:8]=1[CH:9]=[N:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1
Reactant: Nc1ccccc1
Reactant: CN(C)CCCOc1ccccc1C=O
Solvent: CCO
Product: CN(C)CCCOc1ccccc1C=Nc1ccccc1
Yield: 83.2 %

Procedure:
A solution of 15 g of 2-(3-dimethylaminopropoxy)benzaldehyde and 8.0 g of aniline (distilled over zinc dust) in 300 ml of ethanol is kept at room temperature for 22 hours, refluxed for 2 hours, and the solvent removed on a rotary evaporator. The residue (21.3 g) is distilled to give 17 g of an oil; boiling point 171°-175° C./0.2 mm of Hg.
Reaction SMILES: [O:1]=[S:2]1[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[CH2:6][N:5]([C:13]2[NH:14][C:15](=O)[C:16]3[S:21][C:20]([CH3:22])=[CH:19][C:17]=3[N:18]=2)[CH2:4][CH2:3]1.[CH2:24]([NH2:28])[CH2:25][CH2:26][NH2:27]>>[CH3:22][C:20]1[S:21][C:16]2[C:15]([NH:27][CH2:26][CH2:25][CH2:24][NH2:28])=[N:14][C:13]([N:5]3[CH2:6][C:7]4[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=4[S:2](=[O:1])[CH2:3][CH2:4]3)=[N:18][C:17]=2[CH:19]=1
Reactant: Cc1cc2nc(N3CCS(=O)c4ccccc4C3)[nH]c(=O)c2s1
Reactant: NCCCN
Product: Cc1cc2nc(N3CCS(=O)c4ccccc4C3)nc(NCCCN)c2s1

Procedure:
The title compound was prepared in analogy to Example 3-1 in Scheme 3 by using 2-(1-oxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylthieno[3,2-d]pyrimidin-4(3H)-one and 1,3-propandiamine. MS obsd. (ESI+) [(M+H)+] 402, 1H NMR (400 MHz, METHANOL-d4) δ ppm 7.78 (d, J=6.6 Hz, 1H), 7.63 (d, J=7.6 Hz, 1H), 7.34-7.44 (m, 2H), 6.80 (s, 1H), 5.29 (m, 2H), 3.69-3.83 (m, 2H), 3.27-3.42 (m, 2H), 2.97 (t, J=6.3 Hz, 2H), 2.49-2.58 (m, 5H), 1.87 (m, 2H).
Reaction SMILES: [N:1]1[C:10]2[C:5](=[CH:6][C:7]([CH:11]=O)=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.[S:13]1[CH2:19][C:17](=[O:18])[NH:16][C:14]1=[S:15].C([O-])(=O)C.[Na+].O>C(O)(=O)C>[N:1]1[C:10]2[C:5](=[CH:6][C:7](/[CH:11]=[C:19]3/[C:17](=[O:18])[NH:16][C:14](=[S:15])[S:13]/3)=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1
Reactant: O=Cc1ccc2ncccc2c1
Reactant: O=C1CSC(=S)N1
Agent: CC(=O)[O-]
Agent: [Na+]
Solvent: CC(=O)O
Solvent: O
Product: O=C1NC(=S)S/C1=C\c1ccc2ncccc2c1
Temperature: 25 °C
Yield: 98.6 %

Procedure:
The suspension of 6-quinolinecarboxaldehyde (6 g, 38 mmol), rhodanine (2-thioxo-4-thiazolidinone) (5.08 g, 38 mmol) and sodium acetate (12.5 g, 152 mmol) in acetic acid (50 mL) was stirred under reflux for 12 h. After cooling to room temperature, water (150 mL) was added. The solid was collected by filtration, washed with water and dried to obtain 5-[1-quinolin-6-yl-meth-(Z)-ylidene]-2-thioxo-thiazolidin-4-one (10.2 g, 98%) as a yellow solid. LC-MS m/e 273 (MH+).
Reaction SMILES: [CH3:1][N:2]1[CH:6]=[C:5]([C:7]2[CH:12]=[CH:11][N:10]=[CH:9][CH:8]=2)[C:4]([C:13]2[CH:18]=[CH:17][C:16]([OH:19])=[CH:15][CH:14]=2)=[N:3]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[N:39]1[C:48]2[C:43](=[CH:44][CH:45]=[CH:46][N:47]=2)[CH:42]=[CH:41][C:40]=1[CH2:49]O.[OH-].[Na+]>O1CCOCC1>[CH3:1][N:2]1[CH:6]=[C:5]([C:7]2[CH:8]=[CH:9][N:10]=[CH:11][CH:12]=2)[C:4]([C:13]2[CH:18]=[CH:17][C:16]([O:19][CH2:49][C:40]3[CH:41]=[CH:42][C:43]4[C:48](=[N:47][CH:46]=[CH:45][CH:44]=4)[N:39]=3)=[CH:15][CH:14]=2)=[N:3]1
Reactant: Cn1cc(-c2ccncc2)c(-c2ccc(O)cc2)n1
Reactant: OCc1ccc2cccnc2n1
Agent: [Na+]
Agent: [OH-]
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1COCCO1
Product: Cn1cc(-c2ccncc2)c(-c2ccc(OCc3ccc4cccnc4n3)cc2)n1
Temperature: 60 °C
Yield: 8.7 %

Procedure:
To a solution of 4-(1-methyl-4-pyridin-4-yl-1H-pyrazol-3-yl)-phenol (72 mg) in dioxane 1.5 ml, was added triphenyl phosphine (121 mg), [1,8]Naphthyridin-2-yl-methanol (69 mg) and di-t-butyl-diazacarboxalate (106 mg) and the reaction mixture heated at 60° C. for 24 h. The reaction mixture was poured into 1 N NaOH, extracted with methylene chloride, dried magnesium sulfate and concentrated. Purification via Prep TLC eluting with 15% methanol/70% ethyl acetate/15% hexanes provided the title compound (9.8 mg). 1H NMR (400 MHz, CDCl3) δ 9.13 (dd, J=4.2, 1.7 Hz, 1H), 8.45 (d, J=5.8 Hz, 2H), 8.23 (d, J=8.3 Hz, 1H), 7.21 (dd, J=8.5, 2.1 Hz, 1H), 7.79 (d, J=8.7 Hz, 1H), 7.57 (s, 1H), 7.52 (m, 1H), 7.37 (d, J=9.1 Hz, 2H), 7.16 (d, J=6.2 Hz, 2H), 7.01 (d, J=8.7 Hz, 2H), 5.47 (s, 2H) 3.94 (s, 3H); MS: (M+H m/z=394.0).
Reaction SMILES: [CH2:1]([O:8][C:9](Cl)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:12][C@@H:13]([CH2:15][OH:16])[CH3:14].C(=O)([O-])[O-].[K+].[K+].C(OCC)(=O)C>O>[CH2:1]([O:8][C:9]([NH:12][C@H:13]([CH3:14])[CH2:15][OH:16])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C(Cl)OCc1ccccc1
Reactant: C[C@@H](N)CO
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CCOC(C)=O
Product: C[C@H](CO)NC(=O)OCc1ccccc1
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 98.2 %

Procedure:
11.42 g of benzyloxycarbonyl chloride were added dropwise to a mixture of 5.00 g of D-alaninol, 18.49 g of potassium carbonate, 15 ml of ethyl acetate and 15 ml of water, and the mixture was stirred at room temperature for 1.5 hours. At the end of this time, the ethyl acetate layer was separated, and the aqueous layer was extracted with ethyl acetate. The ethyl acetate layer and the extract were combined, dried over anhydrous sodium sulfate and then concentrated by evaporation under reduced pressure. The crude crystals which precipitated were collected by filtration and washed with hexane, to give 13.68 g of the title compound, melting at 78° C. to 80° C.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([CH2:11][C:12]2[CH:17]=[CH:16][N:15]=[CH:14][CH:13]=2)(=[O:10])=[O:9])=[CH:4][CH:3]=1.[CH3:18][N:19]([CH3:23])[CH2:20][CH2:21]O.C(C=P(CCCC)(CCCC)CCCC)#N>C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([S:8]([CH:11]([C:12]2[CH:13]=[CH:14][N:15]=[CH:16][CH:17]=2)[CH2:21][CH2:20][N:19]([CH3:23])[CH3:18])(=[O:9])=[O:10])=[CH:6][CH:7]=1
Reactant: O=S(=O)(Cc1ccncc1)c1ccc(Cl)cc1
Reactant: CN(C)CCO
Agent: CCCCP(=CC#N)(CCCC)CCCC
Solvent: Cc1ccccc1
Product: CN(C)CCC(c1ccncc1)S(=O)(=O)c1ccc(Cl)cc1
Temperature: 25 °C
Yield: 55.4 %

Procedure:
A toluene (5 ml) solution of the 4-(4-chlorophenylsulfonylmethyl)pyridine (70 mg, 0.261 mmol) obtained in Example 119, 2-dimethylaminoethanol (54 μl, 0.538 mmol) and cyanomethylenetri-n-butylphosphorane (129 mg, 0.538 mol) was heated under reflux for 3 days under an argon atmosphere. After cooling to room temperature, the reaction mixture was added with 2-dimethylaminoethanol (54 μl, 0.538 mmol) and cyanomethylenetri-n-butylphosphorane (129 mg, 0.538 mol), followed by heating under reflux for 22 hours under an argon atmosphere. After cooling to room temperature, the reaction mixture was concentrated under reduced pressure. The residue was subjected to chromatography on a silica gel column, and the fraction obtained from the methanol:methylene chloride (=1:10) eluate was concentrated under reduced pressure. The residue thus obtained was purified by high performance liquid chromatography (using a mixed solvent of water/acetonitrile/formic acid) to give the title compound (49 mg, 55%) as a white solid. The resulting solid was washed with hexane-ether and then, collected by filtration, whereby the title compound was obtained as a white powder.
Reaction SMILES: [CH:1]1[C:13]2[NH:12][C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1.[H-].[Na+].Br[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][C:23]([O:25][CH2:26][CH3:27])=[O:24]>>[CH2:26]([O:25][C:23](=[O:24])[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18][CH2:17][N:12]1[C:11]2[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=2[C:5]2[C:13]1=[CH:1][CH:2]=[CH:3][CH:4]=2)[CH3:27]
Reactant: CCOC(=O)CCCCCCBr
Reactant: c1ccc2c(c1)[nH]c1ccccc12
Agent: [H-]
Agent: [Na+]
Product: CCOC(=O)CCCCCCn1c2ccccc2c2ccccc21
Temperature: 50 °C
Reaction time: 0.33 h
Yield: 66.3 %

Procedure:
A RB flask fitted with reflux condenser containing carbazole (0.60 g, 3.59 mmol) and sodium hydride (60 wt. % in mineral oil, 0.22 g, 5.38 mmol) was vacuum purged and filled with argon, followed by addition of DMF (16 mL). After stirring at 50° C. for 20 min, ethyl 7-bromo-heptanoate (0.85 g, 3.59 mmol) was added and the mixture stirred at 80° C. overnight. The reaction was quenched by addition of 5% aqueous NH4Cl (75 mL), transferred to a separatory funnel and extracted with ethyl acetate (3×30 mL). The combined organic layers were washed with brine (2×20 L), dried (Na2SO4) and concentrated. Purification by MPCC (0-50% gradient of ethyl acetate in hexane) afforded the title compound (0.77 g, 66%). 1H NMR (300 MHz, CDCl3): 8.15 (d, 2H, J=7.8 Hz), 7.52 (t, 2H, J=7.3 Hz), 7.44 (d, 2H, J=8.1 Hz), 7.28 (t, 2H, J=7.7 Hz), 4.32 (t, 2H, J=7.2 Hz), 4.16 (q, 2H, J=7.1 Hz), 2.30 (t, 2H, J=7.4 Hz), 1.91 (m, 2H), 1.64 (m, 2H), 1.41 (m, 4H), 1.30 (t, 3H, J=7.2 Hz). 13C NMR APT (100 MHz, CDCl3): 173.7 (up), 140.5 (up), 125.6 (down), 122.9 (up), 120.4 (down), 118.8 (down), 108.7 (down), 60.3 (up), 43.0 (up), 34.3 (up), 28.9 (up), 27.0 (up), 24.8 (up), 14.3 (down). ESI-HRMS (m/z): [M+H]+ calcd. for C21H25NO2, 324.1958. found, 324.1957
Reaction SMILES: [OH:1][CH2:2][C:3]1[C:7]2[NH:8][C:9]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[CH:10][C:6]=2[O:5][CH:4]=1>C(Cl)Cl.O=[Mn]=O>[CH:2]([C:3]1[C:7]2[NH:8][C:9]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[CH:10][C:6]=2[O:5][CH:4]=1)=[O:1]
Reactant: CCOC(=O)c1cc2occ(CO)c2[nH]1
Agent: O=[Mn]=O
Solvent: ClCCl
Product: CCOC(=O)c1cc2occ(C=O)c2[nH]1
Temperature: 25 °C
Reaction time: 8 h
Yield: 91.8 %

Procedure:
To a solution of ethyl 3-hydroxymethyl-4H-furo[3,2-b]pyrrole-5-carboxylate (1.1 g, 5.26 mmol) in CH2Cl2 (100 mL) was added MnO2 (4.6 g, 52.6 mmol). The reaction mixture was stirred at rt overnight and was then filtered through Celite® and washed with CH2Cl2 (3×50 mL). The organic solution was concentrated in vacuo and chromatographed over silica gel (0 to 40% EtOAc in heptane over 30 min) to give ethyl 3-formyl-4H-furo[3,2-b]pyrrole-5-carboxylate (1.0 g, 92%) as light yellow solid. 1H NMR (400 MHz, CDCl3) δ ppm 1.41 (t, J=7.13 Hz, 3-H) 4.40 (q, J=7.13 Hz, 2H) 6.83 (dd, J=1.54, 1.00 Hz, 1H) 7.23 (d, J=0.88 Hz, 1H) 8.98 (br. s., 1H) 9.67 (s, 1H).
Reaction SMILES: [CH2:1]([O:5][C:6]1[CH:25]=[CH:24][C:9]([C:10]([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[CH:14][CH:13]=2)=[S:11])=[C:8]([OH:26])[CH:7]=1)[CH:2]1[O:4][CH2:3]1.[OH2:27]>O1CCCC1>[OH:4][CH:2]([CH2:3][OH:27])[CH2:1][O:5][C:6]1[CH:25]=[CH:24][C:9]([C:10]([C:12]2[CH:13]=[CH:14][C:15]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[CH:16][CH:17]=2)=[S:11])=[C:8]([OH:26])[CH:7]=1
Reactant: O
Reactant: Oc1cc(OCC2CO2)ccc1C(=S)c1ccc(-c2ccccc2)cc1
Solvent: C1CCOC1
Product: OCC(O)COc1ccc(C(=S)c2ccc(-c3ccccc3)cc2)c(O)c1

Procedure:
The tide compound is prepared by the reaction of the compound of Example 14 with water in the presence of mineral acid in tetrahydrofuran.