Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[C:7]([CH3:9])[C:6]([S:10]([N:13]([CH3:28])[CH2:14][C:15]2[O:16][C:17]([C:20]([N:22]3[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]3)=[O:21])=[N:18][N:19]=2)(=[O:12])=[O:11])=[C:5]([CH3:29])[CH:4]=1.[CH3:30][N:31]1[C:35]([CH:36]=O)=[CH:34][N:33]=[CH:32]1.ClCCCl>>[CH3:1][O:2][C:3]1[CH:8]=[C:7]([CH3:9])[C:6]([S:10]([N:13]([CH3:28])[CH2:14][C:15]2[O:16][C:17]([C:20]([N:22]3[CH2:23][CH2:24][N:25]([CH2:36][C:35]4[N:31]([CH3:30])[CH:32]=[N:33][CH:34]=4)[CH2:26][CH2:27]3)=[O:21])=[N:18][N:19]=2)(=[O:11])=[O:12])=[C:5]([CH3:29])[CH:4]=1
Reactant: COc1cc(C)c(S(=O)(=O)N(C)Cc2nnc(C(=O)N3CCNCC3)o2)c(C)c1
Reactant: Cn1cncc1C=O
Solvent: ClCCCl
Product: COc1cc(C)c(S(=O)(=O)N(C)Cc2nnc(C(=O)N3CCN(Cc4cncn4C)CC3)o2)c(C)c1

Procedure:
The title compound was prepared according to general procedure CD using 4-methoxy-N,2,6-trimethyl-N-{[5-(piperazin-1-ylcarbonyl)-1,3,4-oxadiazol-2-yl]methyl}benzenesulfonamide (42 mg, 0.10 mmol), 1-methyl-1H-imidazole-5-carbaldehyde (13 mg, 0.12 mmol), STAB (42 mg, 0.2 mmol) DCE (0.8 mL) and a few 4 Å molecular sieves. The crude product was purified using prep method D.
Reaction SMILES: [CH:1]1([NH2:6])[CH2:5][CH2:4][CH2:3][CH2:2]1.C(O)(=O)C.C([BH3-])#N.[Na+].[CH2:15]([O:17][C:18](=[O:28])[C:19]([CH:26]=O)([CH3:25])[CH2:20][CH2:21][CH:22]([CH3:24])[CH3:23])[CH3:16]>C(O)C>[CH2:15]([O:17][C:18](=[O:28])[C:19]([CH2:25][NH:6][CH:1]1[CH2:5][CH2:4][CH2:3][CH2:2]1)([CH3:26])[CH2:20][CH2:21][CH:22]([CH3:23])[CH3:24])[CH3:16]
Reactant: CCOC(=O)C(C)(C=O)CCC(C)C
Reactant: NC1CCCC1
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CCO
Solvent: CC(=O)O
Product: CCOC(=O)C(C)(CCC(C)C)CNC1CCCC1
Temperature: 25 °C
Reaction time: 18 h
Yield: 39.3 %

Procedure:
Cyclopentylamine (1.49 mL, 15.1 mmol), glacial acetic acid (1.5 mL), and sodium cyanoborohydride (1.90 g, 30.2 mmol) were added sequentially to a solution of crude rac-2-formyl-2,5-dimethyl-hexanoic acid ethyl ester (prepared as described in Example 19c; 3.02 g, 15.1 mmol) in ethanol (45 mL) at 25° C. The mixture was stirred at 25° C. for 18 h, and then was concentrated in vacuo. The residue was partitioned between half-saturated aqueous sodium bicarbonate solution (150 mL) and ethyl acetate (2×150 mL). The combined organic layers were dried over sodium sulfate and were concentrated in vacuo. The residue was purified by flash column chromatography (self-packed glass column, gradient elution: 20-30% ethyl acetate in hexanes) to afford rac-2-cyclopentylaminomethyl-2,5-dimethyl-hexanoic acid ethyl ester (1.60 g, 5.94 mmol, 39%) as a pale yellow oil. 1H NMR (400 MHz, CDCl3) δ: 0.87 (6H, d, J=6.9 Hz), 1.01-1.06 (1H, m), 1.16 (3H, s), 1.27 (3H, t, J=6.9 Hz), 1.27-1.33 (4H, m), 1.43-1.64 (8H, m), 2.51 (1H, d, J=11.7 Hz), 2.79 (1H, d, J=11.7 Hz), 2.96-3.02 (1H, m), 4.12 (2H, q, J=7.2 Hz).
Reaction SMILES: [CH:1]1([CH2:6][N:7]([CH2:22][CH:23]=[CH2:24])[CH:8]([CH3:21])[CH2:9][CH2:10][CH2:11][C:12]([C:14]2[CH:19]=[CH:18][C:17](F)=[CH:16][CH:15]=2)=[O:13])[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH:25]1[CH:29]=[CH:28][N:27]=[CH:26]1>>[CH:1]1([CH2:6][N:7]([CH2:22][CH:23]=[CH2:24])[CH:8]([CH3:21])[CH2:9][CH2:10][CH2:11][C:12]([C:14]2[CH:19]=[CH:18][C:17]([N:25]3[CH:29]=[CH:28][N:27]=[CH:26]3)=[CH:16][CH:15]=2)=[O:13])[CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: C=CCN(CC1CCCC1)C(C)CCCC(=O)c1ccc(F)cc1
Reactant: c1c[nH]cn1
Product: C=CCN(CC1CCCC1)C(C)CCCC(=O)c1ccc(-n2ccnc2)cc1

Procedure:
In a manner similar to Example 26, react 5-[(cyclopentylmethyl)(2-propenyl)amino]-1-(4-fluorophenyl)hexan-1-one with 1H-imidazole to obtain the title compound.
Reaction SMILES: [F:1][C:2]([F:16])([F:15])[C:3]1[CH:4]=[C:5]([CH:8]=[C:9]([C:11]([F:14])([F:13])[F:12])[CH:10]=1)[CH2:6][NH2:7].[CH:17]([O:20][C:21]([N:23]1[C:36]2[C:28](=[CH:29][C:30]3[CH2:31][CH2:32][CH2:33][C:34]=3[CH:35]=2)[C:27](=O)[CH2:26][CH2:25][CH2:24]1)=[O:22])([CH3:19])[CH3:18].[BH4-].[Na+]>CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-].CO>[CH:17]([O:20][C:21]([N:23]1[C:36]2[C:28](=[CH:29][C:30]3[CH2:31][CH2:32][CH2:33][C:34]=3[CH:35]=2)[CH:27]([NH:7][CH2:6][C:5]2[CH:4]=[C:3]([C:2]([F:15])([F:16])[F:1])[CH:10]=[C:9]([C:11]([F:14])([F:12])[F:13])[CH:8]=2)[CH2:26][CH2:25][CH2:24]1)=[O:22])([CH3:19])[CH3:18]
Reactant: NCc1cc(C(F)(F)F)cc(C(F)(F)F)c1
Reactant: CC(C)OC(=O)N1CCCC(=O)c2cc3c(cc21)CCC3
Agent: [Ti+4]
Agent: CC(C)[O-]
Agent: [BH4-]
Solvent: CO
Product: CC(C)OC(=O)N1CCCC(NCc2cc(C(F)(F)F)cc(C(F)(F)F)c2)c2cc3c(cc21)CCC3
Reaction time: 72 h
Yield: 61.1 %

Procedure:
Add 3,5-bis(trifluoromethyl)benzylamine (187 mg, 0.77 mmol) followed by titanium isopropoxide (835 mg, 2.94 mmol) to 9-oxo-2,3,6,7,8,9-hexahydro-1H-5-aza-cyclohepta[f]indene-5-carboxylic acid isopropyl ester (200 mg, 0.7 mmol) at room temperature under an atmosphere of nitrogen and stir the solution for 3 days. Add methanol (3 mL) and sodium borohydride (40 mg, 1.05 mmol) and stir the mixture under nitrogen at room temperature for 16 h. Add sodium bicarbonate saturated solution, filter through Celite® and wash the residue with ethyl acetate. Separate organic layer, extract aqueous with ethyl acetate. Wash organic layer with brine and dry the organic layers over anhydrous sodium sulfate. Filter and remove the solvent under reduced pressure. Purify the residue by silica cartridge, eluting with hexanes/ethyl acetate 9:1, to afford (+/−)-isopropyl-9-(3,5-bis-trifluoromethyl-benzylamino)-2,3,6,7,8,9-hexahydro-1H-5-aza-cyclohepta[f]indene-5-carboxylate (220 mg).
Reaction SMILES: [F:1][C:2]([F:39])([F:38])[C:3]1[CH:4]=[C:5]([C:13]([CH3:37])([CH3:36])[C:14]([N:16]([C:18]2[C:19]([O:28][C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=3[CH3:35])=[N:20][C:21](S(C)(=O)=O)=[N:22][CH:23]=2)[CH3:17])=[O:15])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.O1[CH2:45][CH2:44]OCC1>>[F:1][C:2]([F:39])([F:38])[C:3]1[CH:4]=[C:5]([C:13]([CH3:37])([CH3:36])[C:14]([N:16]([CH3:17])[C:18]2[C:19]([O:28][C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=3[CH3:35])=[N:20][C:21]([N:16]3[CH2:45][CH2:44][NH:22][CH2:23][CH2:18]3)=[N:22][CH:23]=2)=[O:15])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1
Reactant: Cc1ccccc1Oc1nc(S(C)(=O)=O)ncc1N(C)C(=O)C(C)(C)c1cc(C(F)(F)F)cc(C(F)(F)F)c1
Reactant: C1COCCO1
Product: Cc1ccccc1Oc1nc(N2CCNCC2)ncc1N(C)C(=O)C(C)(C)c1cc(C(F)(F)F)cc(C(F)(F)F)c1
Reaction time: 16 h
Yield: 132.3 %

Procedure:
To a solution of 0.30 g (0.52 mmol) 2-(3,5-bis-trifluoromethyl-phenyl)-N-(2-methanesulfonyl-4-o-tolyloxy-pyrimidin-5-yl)-N-methyl-isobutyramide in 10 ml dioxane 0.112 g (1.3 mmol) piperazine was added. The reaction mixture was stirred for 16 hrs. After evaporation of the solvent, the residue was distributed between 50 ml CH2Cl2 and 50 ml sat. NaHCO3-solution. The aqueous layer was extracted with 50 ml CH2Cl2, the combined organic layers dried (MgSO4), filtered and evaporated. The residue was purified by chromatography (SiO2, CH2Cl2/MeOH/NH4OH 140:10:1) to give 0.20 g (66%) 2-(3,5-bis-trifluoromethyl-phenyl)-N-methyl-N-(2-piperazin-1-yl-4-o-tolyloxy-pyrimidin-5-yl)-isobutyramide as a white foam, MS (ISP): 582.2 (M+H)+.
Reaction SMILES: II.I[CH2:4]I.[Br:6][C:7]1[CH:8]=[C:9]([CH:12]=[CH:13][CH:14]=1)[CH:10]=[CH2:11]>C1(C)C=CC=CC=1.[Cu]>[Br:6][C:7]1[CH:8]=[C:9]([CH:10]2[CH2:4][CH2:11]2)[CH:12]=[CH:13][CH:14]=1
Reactant: ICI
Reactant: C=Cc1cccc(Br)c1
Agent: [Cu]
Agent: II
Solvent: Cc1ccccc1
Product: Brc1cccc(C2CC2)c1
Yield: 10.6 %

Procedure:
Iodine (0.335 g, 1.32 mmol), diiodomethane (4.3 mL, 53.0 mmol) and 3-bromostyrene (5 g, 26.4 mmol) were added successively to a suspension of copper (7.5 g, 118.8 mmol) in toluene (50 mL). The mixture was refluxed for 140 h, then filtered and concentrated in vacuo. The residue was distilled under reduced pressure to afford 3-bromo-1-cyclopropylbenzene (0.55 g, 10%) as a colorless oil.
Reaction SMILES: [CH3:1][C:2]1[NH:3][C:4]2[C:9]([CH:10]=1)=[CH:8][C:7]([CH3:11])=[CH:6][CH:5]=2.Cl[C:13]1[C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=2[S:15][N:14]=1>>[CH3:1][C:2]1[NH:3][C:4]2[C:9]([C:10]=1[C:13]1[C:17]3[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=3[S:15][N:14]=1)=[CH:8][C:7]([CH3:11])=[CH:6][CH:5]=2
Reactant: Cc1ccc2[nH]c(C)cc2c1
Reactant: Clc1nsc2ccccc12
Product: Cc1ccc2[nH]c(C)c(-c3nsc4ccccc34)c2c1

Procedure:
The sub-title compound was prepared by the method of Example 10 part a, using 2,5-dimethyl indole and 3-chloro-1,2-benzisothiazole.
Reaction SMILES: [CH3:1][C:2]1[C:6]([C:7]([OH:9])=[O:8])=[CH:5][NH:4][N:3]=1.S(=O)(=O)(O)O.C([O-])(O)=O.[Na+].[CH2:20](O)[CH3:21]>>[CH3:1][C:2]1[C:6]([C:7]([O:9][CH2:20][CH3:21])=[O:8])=[CH:5][NH:4][N:3]=1
Reactant: Cc1n[nH]cc1C(=O)O
Reactant: CCO
Agent: O=C([O-])O
Agent: O=S(=O)(O)O
Agent: [Na+]
Product: CCOC(=O)c1c[nH]nc1C
Temperature: 25 °C
Yield: 58 %

Procedure:
To a solution of 3-methyl-1H-pyrazole-4-carboxylic acid (2.986 g, 23.68 mmol) in ethanol (20 ml) was added concentrated sulphuric acid (1 ml). The reaction was heated at reflux for 6 hours, cooled to room temperature, and then poured into a saturated aqueous solution of NaHCO3. The mixture was extracted with dichloromethane (3×50 ml) then the combined organic extracts dried over MgSO4 and concentrated in vacuo. The product crystallised on standing (2.105 g, 58% yield).
Reaction SMILES: [CH3:1][N:2]1[C:11](=[O:12])[C:10]2[NH:9][CH:8]=[N:7][C:6]=2[N:5]([CH3:13])[C:3]1=[O:4].Br[CH2:15][CH2:16][CH2:17][P:18]([O:23][CH2:24][CH3:25])(=[O:22])[O:19][CH2:20][CH3:21]>>[CH3:1][N:2]1[C:11](=[O:12])[C:10]2[N:9]([CH2:15][CH2:16][CH2:17][P:18](=[O:22])([O:23][CH2:24][CH3:25])[O:19][CH2:20][CH3:21])[CH:8]=[N:7][C:6]=2[N:5]([CH3:13])[C:3]1=[O:4]
Reactant: CCOP(=O)(CCCBr)OCC
Reactant: Cn1c(=O)c2[nH]cnc2n(C)c1=O
Product: CCOP(=O)(CCCn1cnc2c1c(=O)n(C)c(=O)n2C)OCC

Procedure:
The title substance was prepared from 1,3-dimethylxanthine and diethyl 3-bromopropanephosphonate analogously to Example 1.
Reaction SMILES: C([O:3][C:4]([C:6]1([C:11]2[CH:20]=[CH:19][C:18]3[C:13](=[CH:14][CH:15]=[C:16]([CH2:21][N:22]4[C:26]5=[N:27][C:28]([CH3:32])=[CH:29][C:30]([CH3:31])=[C:25]5[N:24]=[C:23]4[CH2:33][CH3:34])[CH:17]=3)[CH:12]=2)[CH2:10][CH:9]=[CH:8][CH2:7]1)=[O:5])C.[OH-].[Na+]>C(O)C>[CH2:33]([C:23]1[N:22]([CH2:21][C:16]2[CH:17]=[C:18]3[C:13](=[CH:14][CH:15]=2)[CH:12]=[C:11]([C:6]2([C:4]([OH:5])=[O:3])[CH2:10][CH:9]=[CH:8][CH2:7]2)[CH:20]=[CH:19]3)[C:26]2=[N:27][C:28]([CH3:32])=[CH:29][C:30]([CH3:31])=[C:25]2[N:24]=1)[CH3:34]
Reactant: CCOC(=O)C1(c2ccc3cc(Cn4c(CC)nc5c(C)cc(C)nc54)ccc3c2)CC=CC1
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: CCc1nc2c(C)cc(C)nc2n1Cc1ccc2cc(C3(C(=O)O)CC=CC3)ccc2c1
Temperature: 25 °C

Procedure:
A solution of the product of Step 4, above (53) (35mg), 2N NaOH (0.5 ml) and 2 ml of ethanol was heated at 80° C. for 20 hours. The reaction mixture was cooled to ambient temperature and the solvent was evaporated. The residue was dissolved in water and extracted (1×5 ml EtOAc). The aqueous solution was then neutralized with concentrated acetic acid and extracted (2×5 ml CHCl3). The combined organics were dried over MgSO4, filtered and concentrated to dryness. The residue was azeotroped with heptane to remove trace amounts of acetic acid. The crude material was diluted with EtOAc and hexanes were added to crash out the product, which was filtered and dried to yield the title compound (54).
Reaction SMILES: [CH3:1][NH:2][S:3]([C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([CH3:12])[CH:7]=1)(=[O:5])=[O:4].[H-].[Na+].Cl[C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([Cl:22])[N:17]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CN(C=O)C>[Cl:22][C:18]1[N:17]=[C:16]([N:2]([CH3:1])[S:3]([C:6]2[CH:11]=[CH:10][CH:9]=[C:8]([CH3:12])[CH:7]=2)(=[O:5])=[O:4])[CH:21]=[CH:20][CH:19]=1
Reactant: Clc1cccc(Cl)n1
Reactant: CNS(=O)(=O)c1cccc(C)c1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21
Solvent: CN(C)C=O
Product: Cc1cccc(S(=O)(=O)N(C)c2cccc(Cl)n2)c1
Reaction time: 0.33 h

Procedure:
N,3-dimethylbenzenesulfonamide (0.250 g, 1.3 mmol) was added to a microwave vial, equipped with a stir bar. Then DMF (3 ml) was added to the mixture, followed by sodium hydride (0.160 g, 6.7 mmol) and allowed the mixture to stir 20 minutes. Then 2,6-dichloropyridine (0.300 g, 2.0 mmol), palladium(II) acetate (0.030 g, 0.13 mmol) and Xantphos (0.024 g) was added to the mixture. The vial was capped and placed into CEM Microwave for 10 minutes at 100° C., while 100 watts of energy was supplied via Powermax® (Simultaneous heating while cooling technology). The reaction was monitored by LC/MS, which showed desired product in the mixture. The mixture was diluted with DCM and saturated sodium bicarbonate solution. The organic layer was extracted with 4:1 DCM/MeOH (3×25 ml). Combined organics, dried over sodium sulfate, filtered and concentrated in vacuo. The crude was purified by ISCO silica-gel chromatography on a 40 gram column, in a gradient of 1-10% EtOAc/Hexanes over 30 minutes. The fractions with desired product were combined and concentrated to give N-(6-chloropyridin-2-yl)-N,3-dimethylbenzenesulfonamide (0.205 g, 51% yield) as a colorless oil. MS (ESI pos. ion) m/z: 297 (MH+). Calc'd exact mass for C13H13ClN2O2S: 296. 1H NMR (400 MHz, chloroform-d): 2.38 (d, J=2.01 Hz, 3H), 3.31 (d, J=2.51 Hz, 3H), 7.11 (d, J=3.51 Hz, 1H), 7.26-7.48 (m, 4H), 7.57-7.67 (m, 2H).
Reaction SMILES: [NH2:1][C:2]1[N:3]([C:11]2[C:16]([CH3:17])=[CH:15][C:14]([CH3:18])=[CH:13][C:12]=2[CH3:19])[C:4]([CH3:10])=[C:5]([CH3:9])[C:6]=1[C:7]#[N:8].[C:20](OC(=O)C)(=[O:22])[CH3:21]>C(O)(=O)C>[C:7]([C:6]1[C:5]([CH3:9])=[C:4]([CH3:10])[N:3]([C:11]2[C:16]([CH3:17])=[CH:15][C:14]([CH3:18])=[CH:13][C:12]=2[CH3:19])[C:2]=1[NH:1][C:20](=[O:22])[CH3:21])#[N:8]
Reactant: CC(=O)OC(C)=O
Reactant: Cc1cc(C)c(-n2c(C)c(C)c(C#N)c2N)c(C)c1
Solvent: CC(=O)O
Product: CC(=O)Nc1c(C#N)c(C)c(C)n1-c1c(C)cc(C)cc1C

Procedure:
The title compound was prepared as a tan solid by the procedure analogous to that of Example 1A starting with the compound of step A and acetic anhydride in acetic acid. The crude material was pure and used directly for the next cyclization step. 1H NMR (CDCl3) δ 1.75(s, 3H), 1.80(s, 6H), 1.95(s, 3H), 2.18(s, 3H), 2.30(s, 3H), 6.60(brs, 1H), 6.93(s, 2H) ppm.
Reaction SMILES: COCC(O[CH:7]([C:26]1[CH:27]=[C:28]2[C:32](=[CH:33][CH:34]=1)[N:31]([CH2:35][O:36][CH2:37][CH2:38][Si:39]([CH3:42])([CH3:41])[CH3:40])[CH:30]=[C:29]2[CH2:43][CH2:44][CH2:45][O:46][CH3:47])[CH:8]([CH2:12][CH:13]([N:23]=[N+]=[N-])[CH:14]1[CH2:18][CH:17]([CH:19]([CH3:21])[CH3:20])[C:16](=[O:22])[O:15]1)[CH:9]([CH3:11])[CH3:10])=O.C(CN)O>C(O)C.[Pd]>[NH2:23][CH:13]([CH:14]1[O:15][C:16](=[O:22])[CH:17]([CH:19]([CH3:21])[CH3:20])[CH2:18]1)[CH2:12][CH:8]([CH2:7][C:26]1[CH:27]=[C:28]2[C:32](=[CH:33][CH:34]=1)[N:31]([CH2:35][O:36][CH2:37][CH2:38][Si:39]([CH3:40])([CH3:42])[CH3:41])[CH:30]=[C:29]2[CH2:43][CH2:44][CH2:45][O:46][CH3:47])[CH:9]([CH3:11])[CH3:10]
Reactant: COCCCc1cn(COCC[Si](C)(C)C)c2ccc(C(OC(=O)COC)C(CC(N=[N+]=[N-])C3CC(C(C)C)C(=O)O3)C(C)C)cc12
Agent: [Pd]
Solvent: NCCO
Solvent: CCO
Product: COCCCc1cn(COCC[Si](C)(C)C)c2ccc(CC(CC(N)C3CC(C(C)C)C(=O)O3)C(C)C)cc12

Procedure:
The stirred solution of 1.86 g of 2-[2 azido-2-(4-isopropyl-5-oxotetrahydrofuran-2-yl)ethyl]-1-[3-(3-methoxypropyl)-1-(2-trimethylsilanylethoxymethyl)-1H-indol-5-yl]-3-methylbutyl methoxyacetate (diastereomer mixture) in 100 ml of ethanol is hydrogenated at 0° C. in the presence of 0.165 ml of ethanolamine and 1.88 g of 10% Pd/C over 6 hours. The reaction mixture is clarified by filtration and the filtrate is concentrated by evaporation. The residue is admixed with 100 ml of 1M sodium hydrogencarbonate solution and extracted with tert-butyl methyl ether (3×). The combined organic phases are dried over sodium sulphate and filtered, and the filtrate is concentrated by evaporation. The crude title compound is obtained as a colourless oil from the residue by means of flash chromatography (SiO2 60 F). Rt=24.2 (gradient II).
Reaction SMILES: [CH2:1]([NH:8][CH2:9][CH2:10][O:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[O:18][CH3:19])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:20]1([S:26]([N:29]2[C:41]3[CH:40]=[CH:39][CH:38]=[C:37]([O:42][CH2:43][CH:44]4[CH2:46][O:45]4)[C:36]=3[C:35]3[C:30]2=[CH:31][CH:32]=[CH:33][CH:34]=3)(=[O:28])=[O:27])[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>C(O)C>[C:20]1([S:26]([N:29]2[C:41]3[CH:40]=[CH:39][CH:38]=[C:37]([O:42][CH2:43][CH:44]([OH:45])[CH2:46][N:8]([CH2:1][C:2]4[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=4)[CH2:9][CH2:10][O:11][C:12]4[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=4[O:18][CH3:19])[C:36]=3[C:35]3[C:30]2=[CH:31][CH:32]=[CH:33][CH:34]=3)(=[O:27])=[O:28])[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1
Reactant: O=S(=O)(c1ccccc1)n1c2ccccc2c2c(OCC3CO3)cccc21
Reactant: COc1ccccc1OCCNCc1ccccc1
Solvent: CCO
Product: COc1ccccc1OCCN(Cc1ccccc1)CC(O)COc1cccc2c1c1ccccc1n2S(=O)(=O)c1ccccc1

Procedure:
7.4 g of benzyl-[2-(2-methoxy-phenoxy)-ethyl]-amine (29 mmol) were dissolved in 47 ml ethanol. To the stirred solution 10 g of 9-benzenesulfonyl-4-oxiranylmethoxy-9H-carbazole (26 mmol) were added and the mixture was heated under reflux for 15 h. The boiling solution was treated with 1 g of activated carbon for 30 min. The activated carbon was filtered off in the heat, and washed with 20 ml ethanol. The ethanol was rotary evaporated (Tbath 40° C., 20 mbar) and the crude material purified by liquid chromatography (eluent toluene/ethyl acetate 4:1), the pure fractions were collected and rotary evaporated (40° C./15 mbar).
Reaction SMILES: C1CO[C:8]23OCC[O:12][C:3]2([C@:4]2([CH2:27][CH2:26][C@H:25]4[C@@H:15]([CH2:16]/[C:17](=[N:28]\[O:29][CH3:30])/[CH:18]5[C@:23]4([CH3:24])[CH2:22][CH2:21][CH2:20][CH2:19]5)[C@@H:6]2[CH2:7]3)[CH3:5])O1.C=C1C2[C@](C)(CCC(=[O:50])C2)[C@@H]2[C@H]([C@H]3[C@@](CC2)(C)C(=O)CC3)C1>>[CH3:30][O:29]/[N:28]=[C:17]1\[CH2:16][C@@H:15]2[C@@H:25]([C@:23]3([CH3:24])[CH:18]\1[CH2:19][C:20](=[O:50])[CH2:21][CH2:22]3)[CH2:26][CH2:27][C@@:4]1([CH3:5])[C@H:6]2[CH2:7][CH2:8][C:3]1=[O:12]
Reactant: C=C1C[C@@H]2[C@H](CC[C@]3(C)C(=O)CC[C@@H]23)[C@@]2(C)CCC(=O)CC12
Reactant: CO/N=C1\C[C@@H]2[C@H](CC[C@@]3(C)[C@H]2CC24OCCOC23OCCO4)[C@@]2(C)CCCCC12
Product: CO/N=C1\C[C@@H]2[C@H](CC[C@]3(C)C(=O)CC[C@@H]23)[C@@]2(C)CCC(=O)CC12
Yield: 70 %

Procedure:
The title compound II-ao was prepared in 70% yield from 3,3:17,17-bis(ethylendioxy)-6-(E)-methoxyiminoandrostane by the procedure described above for the preparation of 6-methyleneandrostane-3,17-dione (II-ac, Prepn. 13). The combined organic extracts were washed with H2O, dried over Na2SO4 and evaporated to dryness. 1H-NMR (300 MHz, acetone-d6, ppm from TMS): δ 3.78 (3H, s), 3.37 (1H, dd), 2.68-1.14 (19H, m), 1.01 (3H, s), 0.98 (3H, s).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[N:11]1[CH2:16][CH2:15][CH2:14][CH2:13][C:12]1=[O:17])[C:5]([OH:7])=O.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.CN1CCOCC1.[Cl:47][C:48]1[CH:61]=[CH:60][C:51]2[NH:52][C:53]([C@@H:55]([NH2:59])[CH2:56][O:57][CH3:58])=[N:54][C:50]=2[CH:49]=1>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[N:11]1[CH2:16][CH2:15][CH2:14][CH2:13][C:12]1=[O:17])[C:5]([NH:59][C@H:55]([C:53]1[NH:52][C:51]2[CH:60]=[CH:61][C:48]([Cl:47])=[CH:49][C:50]=2[N:54]=1)[CH2:56][O:57][CH3:58])=[O:7]
Reactant: O=C(O)c1ccc(N2CCCCC2=O)c(Cl)c1
Reactant: COC[C@H](N)c1nc2cc(Cl)ccc2[nH]1
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[B-](F)(F)F
Solvent: CN(C)C=O
Solvent: CN1CCOCC1
Product: COC[C@H](NC(=O)c1ccc(N2CCCCC2=O)c(Cl)c1)c1nc2cc(Cl)ccc2[nH]1

Procedure:
Prepared analogously to Example 1f from 3-chloro-4-(piperidin-2-on-1-yl)-benzoic acid, TBTU, NMM and (1R)-1-(5-chloro-1H-benzimidazol-2-yl)-2-methoxy-ethylamine in DMF and subsequent purification by chromatography on silica gel (eluting gradient: ethyl acetate/ethanol 95:5->90:10).
Reaction SMILES: [C@H:1]1([N:12](C)[C@@H:13]([CH2:17][C:18]2[CH:25]=[C:23]([OH:24])[C:21]([OH:22])=[CH:20][CH:19]=2)[C:14]([OH:16])=[O:15])[O:9][C@H:8]([CH2:10][OH:11])[C@@H:6]([OH:7])[C@H:4]([OH:5])[C@H:2]1[OH:3].CN[C@@H](CC1C=C(O)C(O)=CC=1)C(O)=[O:31]>>[CH3:1][NH:12][C@@H:13]([CH2:17][C:18]1[CH:25]=[C:23]([OH:24])[C:21]([OH:22])=[CH:20][CH:19]=1)[C:14]([OH:16])=[O:15].[OH:31][C@H:1]1[O:9][C@H:8]([CH2:10][OH:11])[C@@H:6]([OH:7])[C@H:4]([OH:5])[C@H:2]1[OH:3]
Reactant: CN([C@@H](Cc1ccc(O)c(O)c1)C(=O)O)[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O
Agent: CN[C@@H](Cc1ccc(O)c(O)c1)C(=O)O
Product: OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@@H]1O

Procedure:
A fraction containing α-glucosyl methyldopa was recovered, concentrated in vacuo and pulverized to obtain a white α-glucosyl methyldopa preparation in the yield of about 55% against the weight of the material methyldopa, d.s.b. High-performance liquid chromatography (HPLC) analysis of the preparation revealed that it contained about 60% 3-α-glucosyl methyldopa and about 40% 4-α-glucosyl methyldopa.
Reaction SMILES: Cl[C:2]([O:4][CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)=[O:3].[NH2:12][C:13]1[C:18]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])=[C:17]([OH:26])[C:16]([C:27]2[CH:31]=[CH:30][O:29][C:28]=2[CH:32]=[O:33])=[CH:15][CH:14]=1>C(OCC)C>[CH2:5]([O:4][C:2]([NH:12][C:13]1[C:18]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])=[C:17]([OH:26])[C:16]([C:27]2[CH:31]=[CH:30][O:29][C:28]=2[CH:32]=[O:33])=[CH:15][CH:14]=1)=[O:3])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1
Reactant: O=C(Cl)OCc1ccccc1
Reactant: CC(C)(C)OC(=O)c1c(N)ccc(-c2ccoc2C=O)c1O
Solvent: CCOCC
Product: CC(C)(C)OC(=O)c1c(NC(=O)OCc2ccccc2)ccc(-c2ccoc2C=O)c1O
Temperature: 25 °C
Reaction time: 2 h
Yield: 47.7 %

Procedure:
Benzyl chloroformate (0.528 g) was added to a stirred solution of tert-butyl 6-amino-3-(2-formylfuran-3-yl)-2-hydroxybenzoate (Intermediate 61, 0.854 g) in diethyl ether (20 mL). The reaction mixture was stirred at room temperature for 2 hours. A further amount of benzyl chloroformate (1.056 g) was added and the resultant mixture stirred at room temperature overnight. The mixture was concentrated in vacuo and the residue was purified by chromatography on silica, eluting with a mixture of ethyl acetate and cyclohexane, with a gradient of 5-15% to give tert-butyl 6-benzyloxycarbonylamino-3-(2-formylfuran-3-yl)-2-hydroxybenzoate (0.588 g) as a yellow solid.
Reaction SMILES: [Mg].[CH3:2][C:3]1[O:9][C:6]([CH:7]=[O:8])=[CH:5][CH:4]=1.[CH2:10](Cl)[C:11]#[CH:12]>[Br-].[Zn+2].[Br-].C(Cl)C#C.O1CCCC1>[OH:8][CH:7]([C:6]1[O:9][C:3]([CH3:2])=[CH:4][CH:5]=1)[CH2:12][C:11]#[CH:10]
Reactant: Cc1ccc(C=O)o1
Reactant: C#CCCl
Agent: [Br-]
Agent: [Mg]
Agent: [Zn+2]
Solvent: C1CCOC1
Product: C#CCC(O)c1ccc(C)o1
Temperature: 10 °C
Yield: 80.3 %

Procedure:
In the same flask as in Example 1, there were charged granular magnesium (24.3 g), dry zinc bromide (16.9 g) and dry tetrahydrofuran (110 g). Propargyl chloride (0.55 g) was added thereto at 10° C. while stirring. The resultant mixture was kept in an adiabatic condition, whereupon the reaction proceeded. When the heat generation stopped, a mixture of 5-methylfurfural (55.06 g), propargyl chloride (47.9 g) and tetrahydrofuran (110 g) was dropwise added to the reaction mixture at 35° C. in 2 hours while stirring under cooling. The resultant mixture was kept at room temperature for 30 minutes while stirring. After completion of the reaction, the reaction mixture was treated in the same manner as in Example 1 to give 2-(1-hydroxy-3-butynyl)-5-methylfuran (60.3 g) in a yield of 81% (based on the starting 5-methylfurfural).