Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][N:2]1[CH2:30][CH2:29][C:5]2[N:6]([CH2:14][CH:15]([C:23]3[CH:28]=[CH:27][N:26]=[CH:25][CH:24]=3)[CH2:16][CH2:17]OS(C)(=O)=O)[C:7]3[CH:8]=[CH:9][C:10]([CH3:13])=[CH:11][C:12]=3[C:4]=2[CH2:3]1.[NH3:31]>>[CH3:1][N:2]1[CH2:30][CH2:29][C:5]2[N:6]([CH2:14][CH:15]([C:23]3[CH:28]=[CH:27][N:26]=[CH:25][CH:24]=3)[CH2:16][CH2:17][NH2:31])[C:7]3[CH:8]=[CH:9][C:10]([CH3:13])=[CH:11][C:12]=3[C:4]=2[CH2:3]1
Reactant: Cc1ccc2c(c1)c1c(n2CC(CCOS(C)(=O)=O)c2ccncc2)CCN(C)C1
Reactant: N
Product: Cc1ccc2c(c1)c1c(n2CC(CCN)c2ccncc2)CCN(C)C1

Procedure:
Methanesulfonic acid-4-(2,8-dimethyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-3-pyridin-4-yl-butyl ester (200 mg, 0.468 mmol) in 10 mL of aqueous ammonia was heated at 100° C. for 1 h. The progress of reaction was monitored by TLC. After consumption of starting material, the reaction mixture was dried and the crude product was purified by reverse phase chromatography to obtain 33 mg of 4-(2,8-dimethyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-3-pyridin-4-yl-butylamine as the TFA salt. 1H NMR (CD3OD, TFA salt) δ (ppm): 8.5 (d, 2H), 7.5 (m, 2H), 7.25 (d, 1H), 7.24 (s, 1H), 7.05 (t, 1H), 4.6 (d, 1H), 4.5 (d, 1H), 4.3 (m, 1H), 4.23 (t, 1H), 3.8 (m, 1H), 3.5 (m, 1H), 3.08 (d, 3H), 2.8 (m, 2H), 2.7 (m, 2H), 2.4 (s, 3H), 2.25 (m, 1H), 2.2 (m, 1H). Separation by chiral HPLC provides enantiomers II-231a-b.
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH3:15].[CH2:16]1[CH2:20][O:19][CH2:18][CH2:17]1>>[CH2:2]([C:18]1[O:19][CH:20]=[CH:16][CH:17]=1)[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:2][CH2:3][CH2:4][CH3:5]
Reactant: C1CCOC1
Reactant: CCCCCCCCCCCCCCBr
Product: CCCCCCCCCCCCCCCCCCc1ccco1
Temperature: 25 °C
Reaction time: 8 h
Yield: 90 %

Procedure:
1-Bromotetradecane (3.0 g, 9.01 mmol) in THF (4 mL) was added dropwise and the resulting solution was warmed to room temperature and stirred overnight. The reaction was quenched with a saturated solution of NH4Cl (5 mL). The organic layer was removed and the aqueous layer extracted with ether (3×5 mL). The combined organic layers were washed with a saturated solution of NaHCO3 (1×5 mL), brine (1×5 mL), dried over MgSO4, filtered and concentrated. The crude residue was passed through a small silica gel plug and recrystallized in methanol to afford the 2-(octadecyl)furan compound (22) (2.61 g, 90% yield).
Reaction SMILES: [C:1]1(=[O:11])[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3](=[O:10])[NH:2]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Br:31][C:32]1[CH:33]=[N:34][N:35]2[CH:40]=[CH:39][C:38]([NH:41][C@@H:42]([CH:45]([CH3:47])[CH3:46])[CH2:43]O)=[N:37][C:36]=12.N(/C(OC(C)C)=O)=N\C(OC(C)C)=O>C1COCC1>[Br:31][C:32]1[CH:33]=[N:34][N:35]2[CH:40]=[CH:39][C:38]([NH:41][C@@H:42]([CH:45]([CH3:47])[CH3:46])[CH2:43][N:2]3[C:3](=[O:10])[C:4]4[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=4)[C:1]3=[O:11])=[N:37][C:36]=12
Reactant: CC(C)[C@@H](CO)Nc1ccn2ncc(Br)c2n1
Reactant: O=C1NC(=O)c2ccccc21
Agent: CC(C)OC(=O)/N=N/C(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: CC(C)[C@@H](CN1C(=O)c2ccccc2C1=O)Nc1ccn2ncc(Br)c2n1
Temperature: 25 °C
Yield: 40.3 %

Procedure:
To a solution of isoindoline-1,3-dione (4.9 g, 34 mmol) in THF cooled to 0° C. was added triphenylphosphine (8.8 g, 34 mmol) and (S)-2-(3-bromopyrazolo[1,5-a]pyrimidin-5-ylamino)-3-methylbutan-1-ol (Example 15, Step 1; 6.7 g, 22 mmol) and the reaction stirred at ambient temperature until all reactants were dissolved. To the reaction was added (E)-diisopropyl diazene-1,2-dicarboxylate (8.2 g, 40 mmol) and the reaction was stirred for 2 hours at ambient temperature. The reaction was concentrated in vacuo and the material chromatographed using 20% EtOAc/dichloromethane as eluent to yield (S)-2-(2-(3-bromopyrazolo[1,5-a]pyrimidin-5-ylamino)-3-methylbutyl)isoindoline-1,3-dione (3.8 g, 40%).
Reaction SMILES: [Cl-].[Cl:2][C:3]1[C:28]([Cl:29])=[C:27]([O:30][CH3:31])[CH:26]=[C:25]([Cl:32])[C:4]=1[CH2:5][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[CH2:33]([O:35][C:36](=[O:47])[CH:37]=[C:38]([CH3:46])[CH:39]=[CH:40][CH:41]=[C:42]([CH:44]=O)[CH3:43])[CH3:34]>>[CH2:33]([O:35][C:36](=[O:47])[CH:37]=[C:38]([CH3:46])[CH:39]=[CH:40][CH:41]=[C:42]([CH3:44])[CH:43]=[CH:5][C:4]1[C:25]([Cl:32])=[CH:26][C:27]([O:30][CH3:31])=[C:28]([Cl:29])[C:3]=1[Cl:2])[CH3:34]
Reactant: CCOC(=O)C=C(C)C=CC=C(C)C=O
Reactant: COc1cc(Cl)c(C[P+](c2ccccc2)(c2ccccc2)c2ccccc2)c(Cl)c1Cl
Agent: [Cl-]
Product: CCOC(=O)C=C(C)C=CC=C(C)C=Cc1c(Cl)cc(OC)c(Cl)c1Cl

Procedure:
By the procedure of Example 1, 2,3,6-trichloro-4-methoxy-benzyltriphenyl-phosphonium chloride is reacted with 7-formyl-3 -methyl-octa-2,4,6-trien-1-oic acid ethyl ester to obtain 9-(2,3,6-trichloro-4-methoxyphenyl)-3,7-dimethyl-nona-2,4,6,8-tetraen-1-oic acid ethyl ester of melting point 126° - 128° C.
Reaction SMILES: C([SiH](CC)CC)C.[Br:8][CH2:9][C:10]([C:12]1[C:17]([CH3:18])=[CH:16][C:15]([NH:19][C:20](=[O:22])[CH3:21])=[C:14]([CH3:23])[CH:13]=1)=O>FC(F)(F)C(O)=O>[Br:8][CH2:9][CH2:10][C:12]1[C:17]([CH3:18])=[CH:16][C:15]([NH:19][C:20](=[O:22])[CH3:21])=[C:14]([CH3:23])[CH:13]=1
Reactant: CC(=O)Nc1cc(C)c(C(=O)CBr)cc1C
Agent: CC[SiH](CC)CC
Solvent: O=C(O)C(F)(F)F
Product: CC(=O)Nc1cc(C)c(CCBr)cc1C
Temperature: 0 °C
Reaction time: 24 h

Procedure:
Triethylsilane 60 mL (375 mmol) was added to trifluoroacetic acid 360 mL and stirred until a homogenous mixture was obtained (15 minutes). This mixture was then added to solid N-[4-(2-bromo-acetyl)-2,5-dimethyl-phenyl]-acetamide 28.88 g (101.64 mmol) in an ice-cooled flask. The flask was capped with a Dryerite-filled tube (as a gas outlet) and the mixture was stirred on ice bath for 1 hour, then at room temperature for 1 day. The reaction mixture was evaporated and the obtained thick residue was suspended in hexane (0.3 L). Water (100 mL) was added and the mixture was stirred and occasionally shaken for about 1 hour. The formed precipitate was collected by filtration, washed repeatedly with plenty of hexane and water, compressed on the frit, dried by air suction, then on high vacuum.
Reaction SMILES: [OH:1][CH2:2][CH:3]([CH2:5][OH:6])[OH:4].[CH:7](=O)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.O>S(=O)(=O)(O)O.C1(C)C=CC=CC=1>[C:8]1([CH:7]2[O:6][CH2:5][CH:3]([OH:4])[CH2:2][O:1]2)[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1
Reactant: O=Cc1ccccc1
Reactant: OCC(O)CO
Agent: O=S(=O)(O)O
Solvent: Cc1ccccc1
Solvent: O
Product: OC1COC(c2ccccc2)OC1

Procedure:
Concentrated sulfuric acid (3 drops) was added to a mixture of glycerol (55.1 g, 0.60 mmol) and benzaldehyde (50.0 g, 0.47 mmol) in toluene (69 mL) and the resulting mixture was heated to reflux in a Dean-Stark water separator under nitrogen. When the separation of water was complete, the solvent was concentrated under reduced pressure to give a white solid which was recrystallized from ether/petroleum ether. Repeated recrystallization from the same solvent gave pure 2-phenyl-1,3-dioxan-5-ol. 1H NMR (300 MHz, CDCl3) δ 7.51-7.48 (m, 2H), 7.41-7.37 (m, 3H), 5.55 (s, 1H), 4.21-4.17 (m, 2H), 4.14-4.10 (m, 2H), 3.63 (s, 1H), 2.78 (bs, 1H).
Reaction SMILES: C(OC([NH:8][C:9]1[CH:28]=[CH:27][CH:26]=[C:25]([CH3:29])[C:10]=1[CH2:11][NH:12][C:13]1[C:14]2[N:15]([C:19]([CH:23]=[O:24])=[C:20]([CH3:22])[N:21]=2)[CH:16]=[CH:17][CH:18]=1)=O)(C)(C)C.FC(F)(F)C(O)=O.C1(OC)C=CC=CC=1>>[NH2:8][C:9]1[CH:28]=[CH:27][CH:26]=[C:25]([CH3:29])[C:10]=1[CH2:11][NH:12][C:13]1[C:14]2[N:15]([C:19]([CH:23]=[O:24])=[C:20]([CH3:22])[N:21]=2)[CH:16]=[CH:17][CH:18]=1
Reactant: Cc1cccc(NC(=O)OC(C)(C)C)c1CNc1cccn2c(C=O)c(C)nc12
Solvent: O=C(O)C(F)(F)F
Solvent: COc1ccccc1
Product: Cc1cccc(N)c1CNc1cccn2c(C=O)c(C)nc12

Procedure:
Starting from 8-(2-tert-butoxycarbonylamino-6-methylbenzylamino)-3-formyl-2-methylimidazo[1,2-a]pyridine (3.6 g), trifluoroacetic acid (15 ml) and anisole (5 ml) according to the procedure described for Example C1 (Method B) gives, after chromatography on silica gel (eluent: toluene/dioxane=9:1) and crystallization from ethyl acetate/cyclohexane, 2.3 g (76%) of the title compound of m.p. 230-234° C.
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([F:9])=[CH:4][C:3]=1[C@H:10]1[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12][C@@H:11]1[C:23]([O:25]C)=[O:24].[OH-].[Li+]>O1CCCC1.CO>[C:19]([O:18][C:16]([N:13]1[CH2:14][CH2:15][C@H:10]([C:3]2[CH:4]=[C:5]([F:9])[C:6]([F:8])=[CH:7][C:2]=2[F:1])[C@@H:11]([C:23]([OH:25])=[O:24])[CH2:12]1)=[O:17])([CH3:22])([CH3:20])[CH3:21]
Reactant: COC(=O)[C@H]1CN(C(=O)OC(C)(C)C)CC[C@@H]1c1cc(F)c(F)cc1F
Agent: [Li+]
Agent: [OH-]
Solvent: CO
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N1CC[C@H](c2cc(F)c(F)cc2F)[C@@H](C(=O)O)C1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
To 3.3 g (15 mmol) of the product of Step B in 200 mL of 3:1 tetrahydrofuran/methanol was added 50 mL (50 mmol) of 1N aqueous lithium hydroxide solution and the resulting solution was stirred at ambient temperature for 16 h, then concentrated and acidified with 100 mL of 1N aqueous hydrochloric acid. The resulting mixture was extracted with three 100-mL portions of ethyl acetate, and the organic phases combined and washed sequentially with 1N hydrochloric acid and saturated aqueous brine (100 mL each). The organic phase was dried over magnesium sulfate, filtered, and evaporated in vacuo to yield the title compound as a colorless foamy solid that was used without further purification. LC/MS 382.4 (M+23).
Reaction SMILES: [Br:1][C:2]1[CH:21]=[CH:20][C:5]([CH2:6][NH:7][C:8](=[O:19])[C:9]2[CH:14]=[C:13]([CH3:15])[C:12]([F:16])=[CH:11][C:10]=2[O:17]C)=[C:4]([F:22])[CH:3]=1.Br.[Na+].[Cl-].C(OCC)(=O)C>C(O)(=O)C>[Br:1][C:2]1[CH:21]=[CH:20][C:5]([CH2:6][NH:7][C:8](=[O:19])[C:9]2[CH:14]=[C:13]([CH3:15])[C:12]([F:16])=[CH:11][C:10]=2[OH:17])=[C:4]([F:22])[CH:3]=1
Reactant: COc1cc(F)c(C)cc1C(=O)NCc1ccc(Br)cc1F
Agent: Br
Agent: [Cl-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CC(=O)O
Product: Cc1cc(C(=O)NCc2ccc(Br)cc2F)c(O)cc1F
Temperature: 120 °C
Yield: 73 %

Procedure:
A stirring suspension of N-(4-bromo-2-fluoro-benzyl)4-fluoro-2-methoxy-5-methyl-benzamide (2.32 g, 6.51 mmol) in a 25% solution of HBr in acetic acid (60 mL, 0.11 M) was equipped with a reflux condenser and heated to 120° C. for 3.5 h. The mixture was allowed to cool and saturated aq NaCl (50 mL) and ethyl acetate (50 mL) were added. The layers were allowed to separate and the organic layer was collected. The aqueous layer was extracted with ethyl acetate (2×50 mL). The combined organics were dried over Na2SO4, filtered, and concentrated to provide an orange powder. Purification of the solid via silica gel flash chromatography (30% ethyl acetate in heptane) provided N-(4-bromo-2-fluoro-benzyl)-4-fluoro-2-hydroxy-5-methyl-benzamide (1.69, 73%) as a white powder: mp 149-150° C.; Rf 0.51 (30% ethyl acetate in heptane); 1H NMR (CDCl3, 300 MHz) δ 12.20 (d, J=1.5, 1H), 7.30-7.29 (m, 2H), 7.26 (s, 1H), 7.14 (d, J=8.1 Hz, 1H), 6.64 (d, J=10.8, 1H), 6.48 (bd s, 1H), 4.62 (d, J=5.7'Hz, 2H), 2.19 (s, 3H); ESI-LC/MS m/z calcd for C15H12BrF2NO2: 355.0. Found 354.0 (M−1)−. Anal. calcd for C15H12BrF2NO2: C, 50.58; H, 3.40; N, 3.93. Found C, 50.65; H, 3.47; N, 3.87.
Reaction SMILES: [Cl:1][C:2]1[CH:9]=[CH:8][CH:7]=[C:6]([Cl:10])[C:3]=1[CH:4]=[O:5].[N+:11]([CH3:14])([O-])=O>>[NH2:11][CH2:14][CH:4]([OH:5])[C:3]1[C:2]([Cl:1])=[CH:9][CH:8]=[CH:7][C:6]=1[Cl:10]
Reactant: O=Cc1c(Cl)cccc1Cl
Reactant: C[N+](=O)[O-]
Product: NCC(O)c1c(Cl)cccc1Cl

Procedure:
The method of Schoenenberger, Archiv. der Pharmazie, 1975, 308(9), 717-719 can be employed. 2,6-Dichlorobenzaldehyde can be reacted with nitromethane and base, followed by reduction of the aliphatic nitro group to yield 1-amino-2-hydroxy-2-(2,6-dichlorophenyl) ethane. This substance can be reacted with 4-nitrobenzaldehyde to yield a mixture of cis-(±) and trans-(±)-5-(2,6-dichlorophenyl)-2-(4-nitrophenyl)-1,3-oxazolidines. The nitrophenyl group can be reduced with tin (II) dichloride or iron powder and ammonium chloride to yield the corresponding aniline. This aniline can be reacted with 2,2-dichloroacetyl chloride and triethylamine to yield a mixture of cis-(±) and trans-(±)-2,2-dichloro-N-[4-[5-(2,6-dichlorophenyl)-2-(1,3-oxazolidinyl)]phenyl]acetamides.
Reaction SMILES: [C:1]1([C@H:7]2[O:12][C@@H:11](OS(C3C=CC(C)=CC=3)(=O)=O)[CH2:10][CH2:9][O:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:24]([O-:27])(=[S:26])[CH3:25].[Na+].C1C=CC=CC=1>CN(C)C=O>[C:24]([S:26][C@@H:11]1[CH2:10][CH2:9][O:8][C@@H:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[O:12]1)(=[O:27])[CH3:25]
Reactant: CC([O-])=S
Reactant: Cc1ccc(S(=O)(=O)O[C@H]2CCO[C@@H](c3ccccc3)O2)cc1
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: c1ccccc1
Product: CC(=O)S[C@@H]1CCO[C@@H](c2ccccc2)O1
Temperature: 117.5 °C
Yield: 43.5 %

Procedure:
In 200 ml of dimethylformamide were dissolved 29.0 g (86.8 mmol) of cis-2-phenyl-4-(p-toluenesulfonyloxy)-1,3-dioxane and 17.0 g (149 mmol) of sodium thioacetate, and the solution was heated at 115 to 120° C. under a nitrogen atmosphere for 1 hour. After cooling, benzene was added to the reaction mixture and the mixture was washed with water, followed by evaporation of the solvent. The thus obtained brown residue was subjected to column chromatography using silica gel and the fractions eluted with a mixed solvent of benzene-hexane (2:1) were collected, followed by recrystallization from a mixed solvent of benzene-hexane to obtain 8.99 g (yield: 43%) of the title compound having a melting point of 95 to 96° C.
Reaction SMILES: [NH2:1][C:2]1[N:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([C:14]3[N:15]([C:32]4[CH:37]=[CH:36][C:35]([Cl:38])=[CH:34][CH:33]=4)[C:16](=[O:31])[C:17]4[N:18]=[CH:19][N:20]([C:23]5[CH:24]=[C:25]([CH:28]=[CH:29][CH:30]=5)[C:26]#[N:27])[C:21]=4[N:22]=3)=[CH:10][CH:9]=2)=[CH:4][CH:3]=1.Cl.C(=O)([O-])[O-].[NH4+:44].[NH4+]>CO>[NH2:1][C:2]1[N:7]=[CH:6][C:5]([C:8]2[CH:9]=[CH:10][C:11]([C:14]3[N:15]([C:32]4[CH:33]=[CH:34][C:35]([Cl:38])=[CH:36][CH:37]=4)[C:16](=[O:31])[C:17]4[N:18]=[CH:19][N:20]([C:23]5[CH:24]=[C:25]([CH:28]=[CH:29][CH:30]=5)[C:26]([NH2:44])=[NH:27])[C:21]=4[N:22]=3)=[CH:12][CH:13]=2)=[CH:4][CH:3]=1
Reactant: [NH4+]
Reactant: N#Cc1cccc(-n2cnc3c(=O)n(-c4ccc(Cl)cc4)c(-c4ccc(-c5ccc(N)nc5)cc4)nc32)c1
Agent: Cl
Agent: O=C([O-])[O-]
Solvent: CO
Product: N=C(N)c1cccc(-n2cnc3c(=O)n(-c4ccc(Cl)cc4)c(-c4ccc(-c5ccc(N)nc5)cc4)nc32)c1

Procedure:
To 3-[6-[4-(6-amino-pyridin-3-yl)-phenyl]-5-(4-chloro-phenyl)-4-oxo-4,5-dihydro-pyrazolo[3,4-d]pyrimidin-1-yl]-benzonitrile (prepared as described in example 44, 0.30 g, 0.58 mmol), methanol saturated with hydrogen chloride gas (15 mL) is added at 0° C. with stirring. The reaction mixture is allowed to reach rt and stirred there for 12 h. The reaction mixture is then concentrated to a dry residue. It is taken in dry methanol (15 mL) and ammonium carbonate (0.540 g, 3.48 mmol) is added. After stirring at rt for 24 h, the reaction mixture is concentrated and the residue obtained is purified by preparative HPLC to afford 3-[2-[4-(6-amino-pyridin-3-yl)-phenyl]-1-(4-chloro-phenyl)-6-oxo-1,6-dihydro-purin-9-yl]-benzamidine. 1H NMR (DMSO-d6, 400 MHz) δ 8.65 (s, 1H), 8.28 (s, 1H), 8.22 (m, 1H), 8.15 (br, 2H), 7.96-8.03 (m, 2H), 7.67 (m, 2H), 7.59 (s, 1H), 7.45-7.50 (m, 9H), 6.47 (d, 1H), 6.15 (br, 1H); LC-MS calculated for C29H21ClN8O (M+H+) 533.2, found 534.0.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:28]=[CH:29][C:30]=1[Cl:31])[CH2:5][N:6]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[C:8]([S:15]([N:17]2[CH2:22][CH2:21][O:20][CH2:19][CH2:18]2)=[O:16])=[C:7]1[C:23]([O:25][CH2:26][CH3:27])=[O:24].[Mn]([O-])(=O)(=O)=[O:33].[K+]>CC(C)=O.O>[Cl:1][C:2]1[CH:3]=[C:4]([CH:28]=[CH:29][C:30]=1[Cl:31])[CH2:5][N:6]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[C:8]([S:15]([N:17]2[CH2:18][CH2:19][O:20][CH2:21][CH2:22]2)(=[O:33])=[O:16])=[C:7]1[C:23]([O:25][CH2:26][CH3:27])=[O:24]
Reactant: O=[Mn](=O)(=O)[O-]
Reactant: CCOC(=O)c1c(S(=O)N2CCOCC2)c2ccccc2n1Cc1ccc(Cl)c(Cl)c1
Agent: [K+]
Solvent: O
Solvent: CC(C)=O
Product: CCOC(=O)c1c(S(=O)(=O)N2CCOCC2)c2ccccc2n1Cc1ccc(Cl)c(Cl)c1
Reaction time: 18 h
Yield: 82.1 %

Procedure:
To a suspension of ethyl N-(3,4-dichlorobenzyl)-3-morpholinosulphinylindole-2-carboxylate (803 mg) in acetone (40 ml) was added a solution of potassium permanganate (528 mg) in water (15 ml). The resulting mixture was stirred for 18 hours. The mixture was poured into water (20 ml) and extracted with diethyl ether, dried (MgSO4) and concentrated to a gum which was purified by column chromatography using iso-hexane:ethyl acetate (3:1) as eluent to give the desired product (681 mg, 82%); NMR d (CDCl3) 1.3 (t, 3H), 3.2-3.2 (m, 4H), 3.7-3.8 (m, 4H), 5.4 (s, 2H), 6.95 (d, 1H), 7.3-7.4 (m, 5H), 8.05 (d, 1H); M/z (+) 499.2 (MH+), 497.3.
Reaction SMILES: [O:1]=[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH2:5][CH2:4][N:3]1[CH:12]([CH:25]([OH:37])[CH2:26][NH:27][S:28]([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)(=[O:30])=[O:29])[CH:13]([NH:21][C:22]([CH3:24])=[O:23])[C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15].CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C1=CC=CC=2)=O>ClCCl.CCOCC>[O:1]=[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH2:5][CH2:4][N:3]1[CH:12]([C:25](=[O:37])[CH2:26][NH:27][S:28]([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)(=[O:30])=[O:29])[CH:13]([NH:21][C:22]([CH3:24])=[O:23])[C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15]
Reactant: CC(=O)NC(C(=O)OC(C)(C)C)C(C(O)CNS(=O)(=O)c1ccccc1)N1CCc2ccccc2C1=O
Agent: CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21
Solvent: ClCCl
Solvent: CCOCC
Product: CC(=O)NC(C(=O)OC(C)(C)C)C(C(=O)CNS(=O)(=O)c1ccccc1)N1CCc2ccccc2C1=O
Yield: 50 %

Procedure:
To 3-(1,2,3,4-tetrahydro-1-oxo-isoquinoline-2-yl)-acetamino-5-benzenesulfonylamino-4-hydroxy-pentanoic acid, tert-butyl ester (0.9 g, 1.7 mMol) in 20 mL of dichloromethane was added 1.1.1-triacetoxy-1.1-dihydro-1.2-benziodoxol-3-(1H)-one (Dess Martin periodinane, 1.08 g, 2.5 mMol). After 2 hours at room temperature the reaction mixture was diluted with ether, filtered, washed with sodium hydrogen carbonate and water, dried over sodium sulfate, and concentrated under reduced pressure. Chromatography over silica (elution with dichloromethane/methanol 15:1) gave 3-(1,2,3,4-tetrahydro-1-oxo-isoquinoline-2-yl)-acetamino-5-benzenesulfonylamino-4-oxo-pentanoic acid, tert-butyl ester (0.45 g).
Reaction SMILES: CC([O:4][C@H:5]1[C:14]2[C@@:15]3([CH3:30])[C@@H:26]([CH2:27][O:28][CH3:29])[O:25][C:23](=[O:24])[C:17]4=[CH:18][O:19][C:20]([C:21](=[O:22])[C:13]=2[C@@H:8]2[CH2:9][CH2:10][C@H:11]([OH:12])[C@@:7]2([CH3:31])[CH2:6]1)=[C:16]34)=O.[CH2:32]([NH:34][CH2:35][CH3:36])[CH3:33]>CO>[CH2:32]([N:34](/[CH:18]=[C:17]1/[C:23](=[O:24])[O:25][C@H:26]([CH2:27][O:28][CH3:29])[C@@:15]2([CH3:30])[C:16]/1=[C:20]([OH:19])[C:21](=[O:22])[C:13]1[C@H:8]3[C@:7]([CH3:31])([CH2:6][C@@H:5]([OH:4])[C:14]2=1)[C@@H:11]([OH:12])[CH2:10][CH2:9]3)[CH2:35][CH3:36])[CH3:33]
Reactant: COC[C@H]1OC(=O)c2coc3c2[C@@]1(C)C1=C(C3=O)[C@@H]2CC[C@H](O)[C@@]2(C)C[C@H]1OC(C)=O
Reactant: CCNCC
Solvent: CO
Product: CCN(/C=C1/C(=O)O[C@H](COC)[C@@]2(C)C1=C(O)C(=O)C1=C2[C@H](O)C[C@]2(C)[C@@H](O)CC[C@@H]12)CC

Procedure:
To a solution of 17-hydroxywortmannin (1100 mg) in methanol (5 mL) is added diethylamine (0.72 mL). After 48 hours the reaction mixture is concentrated under vacuum. The residue is dissolved in EtOAc and precipitated with hexane. A yellow powder is obtained (0.29 mg). MS: 462.2 (M+H)+.
Reaction SMILES: [OH:1][CH2:2][CH2:3][N:4]1[CH2:8][CH2:7][CH2:6][C:5]1=[O:9].[CH3:10][S:11](Cl)(=[O:13])=[O:12]>N1C=CC=CC=1>[CH3:10][S:11]([O:1][CH2:2][CH2:3][N:4]1[CH2:8][CH2:7][CH2:6][C:5]1=[O:9])(=[O:13])=[O:12]
Reactant: O=C1CCCN1CCO
Reactant: CS(=O)(=O)Cl
Solvent: c1ccncc1
Product: CS(=O)(=O)OCCN1CCCC1=O
Temperature: 25 °C
Reaction time: 8 h
Yield: 72.4 %

Procedure:
To a Stirred solution of 1-(2-hydroxyethyl)pyrrolidin-2-one (2.6 g, 20 mmol) in pyridine (15 ml) was added methanesulfonyl chloride (2.28 g, 20 mmol) and the reaction mixture was stirred at RT overnight. Solution was concentrated and diluted with ethyl acetate (50 ml) and washed with water (50 ml). Ethyl acetate layer was separated, dried over anhydrous sodium sulfate and evaporated to yield 3.0 g of 2-(2-oxopyrrolidin-1-yl)ethyl methanesulfonate, as an oil (yield: 75%).
Reaction SMILES: [CH3:1][N:2]([C:6]1[C:7]2[CH:20]=[CH:19][CH:18]=[CH:17][C:8]=2[S:9][C:10]=1[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)CCC.C(O)=[O:22]>O>[CH:1]([NH:2][C:6]1[C:7]2[CH:20]=[CH:19][CH:18]=[CH:17][C:8]=2[S:9][C:10]=1[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=[O:22]
Reactant: CCCN(C)c1c(-c2ccccc2)sc2ccccc12
Reactant: O=CO
Solvent: O
Product: O=CNc1c(-c2ccccc2)sc2ccccc12

Procedure:
Preparation of the starting product by reduction of the 3-formamido-2-phenyl-benzo(b)thiophene which can be isolated either by drying of the intermediate product formed from preparation of the 3-amino-2-phenyl-benzo(b)thiophene from the 2-phenyl-benzo(b)thiophen-3-ol produced as an intermediate product (described following Example 14) by heating for 1 hour the 3-amino-2-phenyl-benzo(b)thiophene with the same quantity of formic acid at 98 to 100%, followed by dissolving in water and drying. In both cases, 3-formamido-2-phenyl-benzo(b)thiophene is obtained in a quantitative yield: thin colourless needles, mp 185°-186° C. (benzene). 3.0 g (11.8 mmol) of this amide and 1.08 g (28.4 mmol) of LiAlH4 in 60 milliliters of absolute dioxan are refluxed with stirring for 30 minutes. Water is added to the cooled reaction mixture to decompose the excess LiAlH4 and, after the addition of approximately 100 milliliters of CH2Cl2, it is stirred for a further 15 minutes. After centrifuging with the addition of a filtration aid the organic phase is dried over K2CO3 and evaporated. The hydrochloride of the solution of the residue is precipitated in a little chloroform by the action of hydrochloric gas: 2.6 g (80% of theory). The hydrochloride of 3-methylamino-2-phenyl(b)thiophene, colourless crystals in ethanol-ether, decomposition from 198° C. (in sealed tube). From this salt the base is released by the action of ammonia: 3-methylamino- 2-phenyl -benzo(b)thiophene, yellow rods, mp 78°-79° C. (methanol).
Reaction SMILES: [Br-].C1([P+](C2C=CC=CC=2)(C2C=CC=CC=2)[CH2:9][C:10]2[CH:15]=[CH:14][C:13]([C:16]([F:19])([F:18])[F:17])=[CH:12][CH:11]=2)C=CC=CC=1.[Cl:32][C:33]1[N:38]=[CH:37][C:36]([CH:39]=O)=[CH:35][CH:34]=1.CC(C)([O-])C.[Na+]>C(O)C>[Cl:32][C:33]1[CH:34]=[CH:35][C:36](/[CH:39]=[CH:9]/[C:10]2[CH:11]=[CH:12][C:13]([C:16]([F:17])([F:18])[F:19])=[CH:14][CH:15]=2)=[CH:37][N:38]=1
Reactant: FC(F)(F)c1ccc(C[P+](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Reactant: O=Cc1ccc(Cl)nc1
Agent: CC(C)(C)[O-]
Agent: [Br-]
Agent: [Na+]
Solvent: CCO
Product: FC(F)(F)c1ccc(/C=C/c2ccc(Cl)nc2)cc1
Reaction time: 1 h
Yield: 24.7 %

Procedure:
Triphenyl[4-(trifluoromethyl)benzyl]phosphonium bromide (6.4 g) and 6-chloropyridine-3-carboxaldehyde (1.8 g) were dissolved in ethanol (120 mL). To the solution, sodium tert-butoxide (1.2 g) was added at room temperature, and the mixture was stirred for 1 hour. The solvent was distilled off under reduced pressure, and ethyl acetate was added to the residue. The organic layer was washed with water and dried over sodium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography (Yamazen Corporation, elution solvent: hexane/ethyl acetate). The obtained solid was washed with hexane to obtain the title compound (0.89 g) (yield: 25%).