Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([C:3]1[CH:11]=[CH:10][C:9]2[NH:8][C:7]3[CH2:12][CH2:13][N:14]([CH3:16])[CH2:15][C:6]=3[C:5]=2[CH:4]=1)[CH3:2].[OH-].[K+].[CH3:19][C:20]1[N:25]=[CH:24][C:23]([CH:26]=[CH2:27])=[CH:22][N:21]=1>CN1CCCC1=O.O>[CH2:1]([C:3]1[CH:11]=[CH:10][C:9]2[N:8]([CH2:27][CH2:26][C:23]3[CH:22]=[N:21][C:20]([CH3:19])=[N:25][CH:24]=3)[C:7]3[CH2:12][CH2:13][N:14]([CH3:16])[CH2:15][C:6]=3[C:5]=2[CH:4]=1)[CH3:2]
Reactant: C=Cc1cnc(C)nc1
Reactant: CCc1ccc2[nH]c3c(c2c1)CN(C)CC3
Agent: [K+]
Agent: [OH-]
Solvent: CN1CCCC1=O
Solvent: O
Product: CCc1ccc2c(c1)c1c(n2CCc2cnc(C)nc2)CCN(C)C1
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 20.8 %

Procedure:
To a solution of 8-Ethyl-2-methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (0.1 g. 0.00046 mol) in N-methyl 2-pyrolidone (1.0 mL) was added powdered potassium hydroxide (0.13 g, 0.0023 mol) and allowed to stir for 10 min at RT. 2-methyl-5-vinyl pyrimidine (0.14 g, 0.00116 mol) was added and stirred for further 3 h. At 80 deg C. After completion (TLC), reaction mixture was diluted with water (15 mL) and extracted with ethyl acetate (3×50 mL). The organic layer was dried over anhydrous sodium sulphate and concentrated under reduced pressure using rotary evaporator. The crude was purified through column chromatography (7% MeOH:DCM in silica 100-200 mesh, Diameter of column—2.5 cm, Height of silica—approx. 5 inch) then purified through preparative TLC. to get the desired compound as yellow oil (0.032 g, 20% yield). 8-Ethyl-2-methyl-5-[2-(2-methyl-pyrimidin-5-yl)-ethyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (0.032 g, 0.000095 mol) was dissolved in THF (1.0 mL). A solution of oxalic acid dihydrate (0.012 g, 0.000095 mol) in THF (1.0 mL) was added and stirred for 30 min at RT, Precipitate obtained was filtered and dried to give oxalate salt as off white solid (0.030 g, 75% yield).
Reaction SMILES: [CH3:1][C:2]([CH:5]1[CH2:11][CH2:10][CH2:9][CH2:8][C:7](OC)=[N:6]1)([CH3:4])[CH3:3].[Cl-:14].[NH4+:15]>CCO>[ClH:14].[CH3:1][C:2]([CH:5]1[NH:6][C:7](=[NH:15])[CH2:8][CH2:9][CH2:10][CH2:11]1)([CH3:4])[CH3:3]
Reactant: [Cl-]
Reactant: COC1=NC(C(C)(C)C)CCCC1
Reactant: [NH4+]
Solvent: CCO
Product: CC(C)(C)C1CCCCC(=N)N1
Product: Cl

Procedure:
The product of EXAMPLE 100 (174 mg, 1.0 mmol) in 10 mL of EtOH was reacted with ammonium chloride (51 mg, 1.0 mmol) by the method of EXAMPLE 27 to yield the crude title material.
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([F:13])=[CH:9][C:10]=2[F:12])[N:5]=[C:4]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[S:20]([CH3:23])(=[O:22])=[O:21])[C:3]=1[CH3:24].[CH3:25][O:26][C:27]1[N:32]=[CH:31][C:30]([C:33]2[C:38]([NH2:39])=[CH:37][C:36]([N:40]3[CH2:45][CH2:44][O:43][CH2:42][CH2:41]3)=[CH:35][N:34]=2)=[CH:29][CH:28]=1>C1(C)C=CC=CC=1>[F:12][C:10]1[CH:9]=[C:8]([F:13])[CH:7]=[C:6]2[C:11]=1[C:2]([NH:39][C:38]1[C:33]([C:30]3[CH:31]=[N:32][C:27]([O:26][CH3:25])=[CH:28][CH:29]=3)=[N:34][CH:35]=[C:36]([N:40]3[CH2:41][CH2:42][O:43][CH2:44][CH2:45]3)[CH:37]=1)=[C:3]([CH3:24])[C:4]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[S:20]([CH3:23])(=[O:22])=[O:21])=[N:5]2
Reactant: Cc1c(-c2ccccc2S(C)(=O)=O)nc2cc(F)cc(F)c2c1Cl
Reactant: COc1ccc(-c2ncc(N3CCOCC3)cc2N)cn1
Solvent: Cc1ccccc1
Product: COc1ccc(-c2ncc(N3CCOCC3)cc2Nc2c(C)c(-c3ccccc3S(C)(=O)=O)nc3cc(F)cc(F)c23)cn1

Procedure:
Essentially prepared according to Procedure H using 4-chloro-5,7-difluoro-3-methyl-2-(2-(methylsulfonyl)phenyl)quinoline (50.0 mg, 0.140 mmol) and 6′-methoxy-5-morpholino-2,3′-bipyridin-3-amine in toluene to give 5,7-difluoro-N-(6′-methoxy-5-morpholino-2,3′-bipyridin-3-yl)-3-methyl-2-(2-(methylsulfonyl)-phenyl)quinolin-4-amine. 1H NMR (CDCl3) δ ppm 8.64 (1H, d, J=1.8 Hz), 8.20 (1H, d, J=7.2 Hz), 8.00 (1H, dd, J=8.5, 2.4 Hz), 7.94 (1H, br. s.), 7.80 (1H, td, J=7.5, 1.4 Hz), 7.70 (1H, td, J=7.7, 1.4 Hz), 7.47 (1H, ddd, J=9.4, 2.4, 1.3 Hz), 7.42 (1H, d, J=7.2 Hz), 6.92-7.04 (2H, m), 6.88 (1H, dd, J=8.6, 0.8 Hz), 6.53 (1H, br. s.), 4.00 (3H, s), 3.78 (4H, t, J=4.7 Hz), 3.02-3.27 (7H, m), 1.97 (3H, s). Mass Spectrum (ESI) m/e=618.2 (M+1).
Reaction SMILES: [CH3:1][CH2:2][O:3][C:4]([C:6]1[N:10]([CH:11]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH3:12])[CH:9]=[N:8][CH:7]=1)=[O:5].[I:19][CH3:20]>ClCCl>[I-:19].[CH2:2]([O:3][C:4]([C:6]1[NH+:10]([CH:11]([C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=2)[CH3:12])[CH2:9][N:8]([CH3:20])[CH:7]=1)=[O:5])[CH3:1]
Reactant: CCOC(=O)c1cncn1C(C)c1ccccc1
Reactant: CI
Solvent: ClCCl
Product: CCOC(=O)C1=CN(C)C[NH+]1C(C)c1ccccc1
Product: [I-]
Temperature: 25 °C
Reaction time: 24 h

Procedure:
To a stirred solution of 7 parts of R-(+) ethyl 1-(1-phenylethyl)-1H-imidazole-5-carboxylate in 19.5 parts of iodomethane were added 21.3 parts of dichloromethane and the whole was stirred for 24 hours at room temperature. The reaction mixture was evaporated and the residue was crystallized from 2-propanol. The product was filtered off and washed with petroleum ether, yielding 7.03 parts of 5-ethoxycarbonyl-3-methyl-1-(1-phenylethyl)-1H-imidazolium iodide; mp. 159.5° C.; [α]D =-62.79° (10% water).
Reaction SMILES: [H-].[Na+].[I:3][C:4]1[CH:9]=[C:8]([C:10]2([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]2)[CH:7]=[CH:6][C:5]=1[OH:22].[CH3:23]I>CN(C=O)C>[I:3][C:4]1[CH:9]=[C:8]([C:10]2([C:16]3[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=3)[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15]2)[CH:7]=[CH:6][C:5]=1[O:22][CH3:23]
Reactant: Oc1ccc(C2(c3ccccc3)CCCCC2)cc1I
Reactant: CI
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COc1ccc(C2(c3ccccc3)CCCCC2)cc1I
Temperature: 0 °C
Reaction time: 2 h

Procedure:
NaH (60% in mineral oil, 60 mg, 1.50 mmol) was added an ice-cooled solution of 2-iodo-4-(1-phenyl-cyclohexyl)-phenol (400 mg, 1.06 mmol) in DMF (10 mL). Methyl iodide (125 μL, 2.0 mmol) was added. The reaction temperature was allowed to reach room temperature. The mixture was stirred for 2 h, then quenched with water 10 mL and extracted with dichloromethane (2×20 mL). The combined organic phase was dried (Na2SO4) and concentrated in vacuo. The residue was taken up in water (20 mL) and extracted with dichloromethane. The organic phase was dried (Na2SO4) and concentrated in vacuo. 1H-nmr of the syrup (430 mg) indicated full conversion to the methyl ether. 1H NMR (400 MHz, CDCl3): 7.71 (d, 1H, J=2.1 Hz), 7.32-7.25 (m, 4H), 7.18 (dd, 1H, J=2.1 Hz, J=8.8 Hz), 7.17-7.13 (m, 1H), 6.72 (d, 1H, J=8.8 Hz), 3.83 (s, 3H), 2.32-2.18 (m, 4H), 1.62-1.44 (m, 6H).
Reaction SMILES: [CH2:1]([Li])CCC.CCCCCC.[CH3:12][N:13]([CH3:27])[C:14]1([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH2:19][CH2:18][C:17](=[O:20])[CH2:16][CH2:15]1.Br[CH2:29][C:30]([O:32][CH3:33])=[O:31].[OH-].[Na+]>C1COCC1>[C:30]([O:32][CH2:33][CH:18]1[CH2:19][C:14]([N:13]([CH3:27])[CH3:12])([C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)[CH2:15][CH2:16][C:17]1=[O:20])(=[O:31])[CH:29]=[CH2:1]
Reactant: [Li]CCCC
Reactant: COC(=O)CBr
Reactant: CN(C)C1(c2ccccc2)CCC(=O)CC1
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CCCCCC
Product: C=CC(=O)OCC1CC(c2ccccc2)(N(C)C)CCC1=O
Temperature: -78 °C
Reaction time: 0.5 h

Procedure:
Diisopropylamine (2.1 ml, 15 mmol) was provided in dry THF (30 ml) in argon and mixed with a solution of butyl lithium in hexane (2.5M, 5 ml, 12.5 mmol) at −30° C. (bath temperature). The reaction mixture was cooled to −78° C. After this temperature was reached, 4-(dimethylamino)-4-phenylcyclohexanone (2.17 g, 10 mmol), dissolved in dry THF (10 ml), was added in drops within 1 min. The batch was left for 30 min at −78° C. Then, methyl bromoacetate (1 ml, 10.6 mmol), dissolved in dry THF (5 ml), was added in drops within 1 min. The reaction mixture was stirred for 1 h at −78° C. After room temperature was reached, the batch was stirred for a further 4 h. After approx. 2 h the batch became cloudy and a precipitate began to separate out. For work up the batch was carefully mixed with water (1 ml), then a mixture of saturated NaCl solution (30 ml) and 2 N HCl (20 ml) was added. The mixture was stirred for 10 min, the organic phase separated and extracted with saturated NaCl solution (2×10 ml). The combined aqueous phases were washed with ethyl acetate (3×20 ml) and then added to a saturated NaHCO3 solution (approx. 30 ml) for neutralisation. The emulsion formed was strongly basified with 2N NaOH and extracted with ethyl acetate (3×30 ml). The combined organic phases were dried over MgSO4 and then concentrated to low volume. The two possible diastereoisomers of the ketone were isolated from the residue (2.53 g) with yields of 710 g (more non-polar diastereoisomer, 24%) and 260 mg (more polar diastereoisomer with an impurity of approx. 10% of a diester, approx. 8%) by means of chromatographic purification [silica gel 60 G (10 g); cyclohexane/ethyl acetate 2:1 (70 ml), cyclohexane/ethyl acetate 1:1 (70 ml), ethyl acetate (70 ml)]. Since according to all observations made hitherto the di-substituted ketones do not react with tryptophol, a further purification of the more polar compound could be omitted.
Reaction SMILES: C(O[CH2:4][CH2:5][CH2:6][CH2:7][O:8]C=C)=C.C#C.[C:13]1(=O)[NH:19][CH2:18][CH2:17]CC[CH2:14]1>>[CH:18]([N:19]1[CH2:13][CH2:14][CH2:4][CH2:5][CH2:6][C:7]1=[O:8])=[CH2:17]
Reactant: C=COCCCCOC=C
Reactant: O=C1CCCCCN1
Agent: C#C
Product: C=CN1CCCCCC1=O
Yield: 85 %

Procedure:
Example 3 was carried out by adding 1% by weight of 1,4-divinyloxybutane as cocatalyst. The amount of ethyne taken up was 0.97 mol per mole of ε-caprolactam. The distillative workup yielded N-vinyl-ε-caprolactam in a yield of 85.0%. A liquid distillation residue was obtained.
Reaction SMILES: [NH:1]1[CH:5]=[N:4][N:3]=[N:2]1.[H-].[Na+].[CH2:8]([N:14]1[C:23]2[C:18](=[CH:19][C:20]([CH3:24])=[CH:21][CH:22]=2)[C:17]([O:25][CH3:26])=[C:16]([CH2:27]Br)[C:15]1=[O:29])[CH2:9][CH2:10][CH2:11][CH2:12][CH3:13]>CN(C)C=O.C(OC(=O)C)C>[CH2:8]([N:14]1[C:23]2[C:18](=[CH:19][C:20]([CH3:24])=[CH:21][CH:22]=2)[C:17]([O:25][CH3:26])=[C:16]([CH2:27][C:5]2[NH:4][N:3]=[N:2][N:1]=2)[C:15]1=[O:29])[CH2:9][CH2:10][CH2:11][CH2:12][CH3:13]
Reactant: c1nnn[nH]1
Reactant: CCCCCCn1c(=O)c(CBr)c(OC)c2cc(C)ccc21
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CCCCCCn1c(=O)c(Cc2nnn[nH]2)c(OC)c2cc(C)ccc21
Temperature: 25 °C
Reaction time: 2 h
Yield: 52.2 %

Procedure:
A solution of tetrazole (0.17 g) in dimethylformamide (2 ml) at ice-bath temperature under nitrogen was stirred with 60% sodium hydride (0.1 g) for 5 mins and then a solution of 1-hexyl-3-bromomethyl-4-methoxy-6-methyl-2(1H)-quinolinone (Example 14, 0.73 g) in dimethylformamide (8 ml) was added to it. The reaction mixture was stirred at room temperature for 2 hours, diluted with ethylacetate and then washed several times with water. The organic layer was dried and evaporated under reduced pressure. The resulting crude reaction product was chromatographed on silica-gel (30 g). Elution with 10% to 20% ethylacetatedichloromethane gave 1-hexyl-3-(1-tetrazolylmethyl)-4-methoxy-6-methyl-2(1H)-quinolinone (0.37 g). That this compound was obtained was confirmed by the spectral data: MS: m/e 355 (M.+); NMR (CDCl3): δ4.18 (s, 3H, OCH3), 5.68 (s, 2H, CH2), 9.14 (s, 1H, CH=).
Reaction SMILES: [F:1][C:2]([F:20])([F:19])[C:3]1[CH:4]=[C:5]([C:13]([CH3:18])([CH3:17])[C:14](O)=[O:15])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.C(Cl)(=O)C([Cl:24])=O>ClCCl.CN(C=O)C>[F:1][C:2]([F:20])([F:19])[C:3]1[CH:4]=[C:5]([C:13]([CH3:18])([CH3:17])[C:14]([Cl:24])=[O:15])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1
Reactant: O=C(Cl)C(=O)Cl
Reactant: CC(C)(C(=O)O)c1cc(C(F)(F)F)cc(C(F)(F)F)c1
Solvent: CN(C)C=O
Solvent: ClCCl
Product: CC(C)(C(=O)Cl)c1cc(C(F)(F)F)cc(C(F)(F)F)c1

Procedure:
15.0 g (50 mmol) 2-(3,5-bis-trifluoromethyl-phenyl)-2-methyl-propionic acid were dissolved in 127.5 ml dichloromethane in the presence of 0.75 ml DMF. 8.76 ml (2 eq.) Oxalyl chloride were added and after 4.5 hours, the solution was rotary evaporated to dryness. 9 ml Toluene were added and the resulting solution was again rotary evaporated, then dried under high vacuum yielding 16.25 g (quant.) of 2-(3,5-bis-trifluoromethyl-phenyl)-2-methyl-propionyl chloride as a yellow oil of 86% purity according to HPLC analysis. NMR (250 MHz, CDCl3): 7.86 (br s, 1H); 7.77, (br s, 2H, 3 Harom); 1.77 (s, 6H, 2 CH3).
Reaction SMILES: [C:1]([O:5][CH:6]([C:11]1[N:16]([CH3:17])[C:15](=[O:18])[C:14]2[NH:19][CH:20]=[CH:21][C:13]=2[C:12]=1[C:22]1[C:23]([CH3:32])=[C:24]2[C:29](=[CH:30][CH:31]=1)[O:28][CH2:27][CH2:26][CH2:25]2)[C:7]([O:9][CH3:10])=[O:8])([CH3:4])([CH3:3])[CH3:2].C([O-])([O-])=O.[Cs+].[Cs+].[F:39][C:40]1[CH:41]=[C:42]([CH:45]=[CH:46][C:47]=1[CH3:48])[CH2:43]Br>C(#N)C.O.Cl>[C:1]([O:5][CH:6]([C:11]1[N:16]([CH3:17])[C:15](=[O:18])[C:14]2[N:19]([CH2:43][C:42]3[CH:45]=[CH:46][C:47]([CH3:48])=[C:40]([F:39])[CH:41]=3)[CH:20]=[CH:21][C:13]=2[C:12]=1[C:22]1[C:23]([CH3:32])=[C:24]2[C:29](=[CH:30][CH:31]=1)[O:28][CH2:27][CH2:26][CH2:25]2)[C:7]([O:9][CH3:10])=[O:8])([CH3:4])([CH3:3])[CH3:2]
Reactant: COC(=O)C(OC(C)(C)C)c1c(-c2ccc3c(c2C)CCCO3)c2cc[nH]c2c(=O)n1C
Reactant: Cc1ccc(CBr)cc1F
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: O
Solvent: CC#N
Product: COC(=O)C(OC(C)(C)C)c1c(-c2ccc3c(c2C)CCCO3)c2ccn(Cc3ccc(C)c(F)c3)c2c(=O)n1C
Temperature: 70 °C
Reaction time: 1.5 h
Yield: 82.6 %

Procedure:
A solution of methyl 2-(tert-butoxy)-2-(6-methyl-4-(5-methylchroman-6-yl)-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-5-yl)acetate (20 mg, 0.046 mmol) in Acetonitrile (0.45 mL) was treated with Cs2CO3 (59.4 mg, 0.182 mmol), 3-fluoro-4-methylbenzyl bromide (13.89 mg, 0.068 mmol), and then stirred at 70° C. for 90 min. The reaction was cooled to rt, diluted with water and 1N HCl, extracted with EtOAc, washed Brine, dried with Na2SO4, filtered, and concentrated. Purification with column chromatography (0-60% EtOAc/Hexane) gave methyl 2-(tert-butoxy)-2-(1-(3-fluoro-4-methylbenzyl)-6-methyl-4-(5-methylchroman-6-yl)-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-5-yl)acetate (21.5 mg, 0.038 mmol, 84% yield) as clear oil: LCMS (m/z) ES+=561 (M+1). The intermediate was dissolved in Methanol (0.5 mL) and Tetrahydrofuran (THF) (0.5 mL), treated with LiOH (0.100 mL, 0.200 mmol), and stirred overnight at 60° C. The reaction was concentrated and purified with reverse phase HPLC (20-100% MeCN/H2O-0.1% TFA) to give title compound (13.5 mg, 0.024 mmol, 64.7% yield) as white solid: 1H NMR (400 MHz, CHLOROFORM-d) ppm 7.36-7.29 (m, 0.4H), 7.12 (t, J=7.8 Hz, 1H), 7.04-6.87 (m, 3.6H), 6.80-6.66 (m, 1H), 5.97-5.59 (m, 3H), 5.46-5.40 (m, 0.4H), 5.21-5.11 (m, 0.6H), 4.27-4.10 (m, 2H), 3.71-3.61 (m, 3H), 2.77-2.58 (m, 2H), 2.27-2.19 (m, 3H), 2.16-2.05 (m, 2H), 2.02 (s, 2H), 1.94 (s, 1H), 1.19-1.11 (m, 6H), 1.05-0.99 (m, 3; LCMS (m/z) ES+=547 (M+1).
Reaction SMILES: C([O:5][C:6]([NH:8][C@@H:9]([CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[C@@H:10]1[O:12][CH2:11]1)=[O:7])(C)(C)C.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C(O)C>[CH2:13]([C@H:9]1[C@H:10]([CH2:11][OH:12])[O:5][C:6](=[O:7])[NH:8]1)[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1
Reactant: CC(C)(C)OC(=O)N[C@@H](Cc1ccccc1)[C@H]1CO1
Agent: O=C(O)CC(O)(CC(=O)O)C(=O)O
Solvent: CCO
Product: O=C1N[C@@H](Cc2ccccc2)[C@H](CO)O1
Temperature: 70 °C
Reaction time: 2 h
Yield: 80 %

Procedure:
To (2S,3S)-3-tert-butoxycarbonylamino-1,2-epoxy-4-phenylbutane obtained in the same manner as in Reference Example 2 (2.75 g) was added ethanol (27.5 ml). 6.8% Aqueous citric acid solution (29.5 g) was then added thereto, and the mixture was stirred at 70° C. for 2 hr. After cooling to room temperature, ethanol was removed under reduced pressure. The residue was extracted with ethyl acetate, dried over anhydrous sodium sulfate and concentrated under reduced pressure. Further, a mixed solvent of hexane (2.5 ml) and ethyl acetate (2.5 ml) was added to allow precipitation of the crystals. The crystals were collected by filtration and washed twice with a mixed solvent of hexane/ethyl acetate (1/1). The obtained crystals were dried to give the objective (4S,5R)-4-benzyl-5-hydroxymethyloxazolidin-2-one (1.79 g) in a yield of 80%.
Reaction SMILES: [O:1]1[C@H:3]2[CH2:4][C@H:5]3[C@:20]([CH3:22])([CH2:21][C@@H:2]12)[C@@H:19]1[C@H:8]([C@H:9]2[C@:16]([CH3:24])([CH2:17][C:18]1=[O:23])[C@@H:12]([C:13](=[O:15])[CH3:14])[CH2:11][CH2:10]2)[CH2:7][CH2:6]3.[N-:25]=[N+:26]=[N-:27].[Na+].O>CS(C)=O.S(=O)(=O)(O)O>[N:25]([C@H:2]1[CH2:21][C@@:20]2([CH3:22])[C@@H:5]([CH2:6][CH2:7][C@@H:8]3[C@@H:19]2[C:18](=[O:23])[CH2:17][C@@:16]2([CH3:24])[C@H:9]3[CH2:10][CH2:11][C@@H:12]2[C:13](=[O:15])[CH3:14])[CH2:4][C@@H:3]1[OH:1])=[N+:26]=[N-:27]
Reactant: CC(=O)[C@H]1CC[C@H]2[C@@H]3CC[C@H]4C[C@@H]5O[C@@H]5C[C@]4(C)[C@H]3C(=O)C[C@]12C
Reactant: [N-]=[N+]=[N-]
Agent: O=S(=O)(O)O
Agent: [Na+]
Solvent: O
Solvent: CS(C)=O
Product: CC(=O)[C@H]1CC[C@H]2[C@@H]3CC[C@H]4C[C@H](O)[C@@H](N=[N+]=[N-])C[C@]4(C)[C@H]3C(=O)C[C@]12C
Yield: 51.3 %

Procedure:
2α,3α-Epoxy-5α-pregnane-11,20-dione (500 mg) was dissolved in dimethylsulphoxide (25 ml) and sodium azide (1.5 g) added to the solution. Concentrated sulphuric acid (10 drops) was added and the mixture heated on a steam bath for 48 hours. The solution was poured into iced water (600 ml) and the precipitate extracted into ether (100 ml). The ether extract was washed with water (4 + 250 ml) and then saturated sodium bicarbonate solution (250 ml) and finally water (250 ml.). The organic solution was dried over anhydrous sodium sulphate and evaporated to a white foam which was purified by preparative T.L.C. using ethyl acetate/petrol (1/1) run twice. The main band gave title compound (290 mg;) as a foam, [α]D + 95° (c, 0.98).
Reaction SMILES: [CH2:1]([CH:8]([C:22]([OH:24])=[O:23])[C:9](O)([CH2:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[C:10]([OH:12])=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(OC(=O)C)(=O)C>CCCCCC.C(OCC)(=O)C>[CH2:1]([C:8]1[C:22]([O:24][C:10](=[O:12])[C:9]=1[CH2:13][CH2:14][C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1)=[O:23])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=C(O)C(Cc1ccccc1)C(O)(CCc1ccccc1)C(=O)O
Solvent: CCOC(C)=O
Solvent: CCCCCC
Solvent: CC(=O)OC(C)=O
Product: O=C1OC(=O)C(Cc2ccccc2)=C1CCc1ccccc1
Temperature: 115 °C
Reaction time: 3 h
Yield: 81 %

Procedure:
To the crude 3-benzyl-2-hydroxy-2-phenethylsuccinic acid obtained was added acetic anhydride (2.5 mL), and the mixture was stirred at 115° C. for 3 h. The acetic anhydride was evaporated under reduced pressure, and the residue thus obtained was subjected to silica gel column chromatography (hexane-ethyl acetate 10:1) to give 180 mg of the title compound as a solid (2 step yield: 81%).
Reaction SMILES: [N:1]1([CH:7]([CH3:16])[C:8]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[O:9])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[Mg].Br[C:19]1[C:24]([O:25][CH3:26])=[C:23]([CH3:27])[CH:22]=[C:21]([C:28]([CH3:31])([CH3:30])[CH3:29])[CH:20]=1.BrCCBr.Cl.N>C(OCC)C>[CH3:26][O:25][C:24]1[C:23]([CH3:27])=[CH:22][C:21]([C:28]([CH3:31])([CH3:30])[CH3:29])=[CH:20][C:19]=1[C:8]([C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1)([OH:9])[CH:7]([N:1]1[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1)[CH3:16]
Reactant: CC(C(=O)c1ccccc1)N1CCCCC1
Reactant: COc1c(C)cc(C(C)(C)C)cc1Br
Agent: Cl
Agent: N
Agent: [Mg]
Solvent: CCOCC
Solvent: BrCCBr
Product: COc1c(C)cc(C(C)(C)C)cc1C(O)(c1ccccc1)C(C)N1CCCCC1
Reaction time: 4 h
Yield: 78.7 %

Procedure:
15 g of α-piperidinopropiophenone were added to a Grignard solution of 7.3 g of magnesium, 38.5 g of 6-bromo-2-methyl-4-tert-butylanisole and 28.2 g of 1,2,-dibromethane in 300 ml of diethyl ether. After boiling for 4 hours under reflux, the reaction mixture was poured on to ice and acidified with hydrochloric acid. The acidic aqueous solution and the oily intermediate layer were both separated, together made alkaline with a concentrated aqueous ammonia solution, and the base which separated therefrom was dissolved in diethyl ether. After evaporation of the diethyl ether, 26.5 g of viscous brown oil were obtained from which, upon trituration of dilution with isopropanol, 21.5 g of 1-(2'-methoxy-3'-methyl-5'-tert-butylphenyl)-1-phenyl-2-piperidino-propan-1-ol, having a melting point of 86° C. to 87° C., crystallized out. The product was recrystallized from isopropanol and then had a melting point of 87° C. to 88° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][CH:11]=1)[C:6](Cl)=[O:7].[F:12][C:13](I)([F:18])[C:14]([F:17])([F:16])[F:15]>C(Cl)Cl>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:6](=[O:7])[C:13]([F:18])([F:12])[C:14]([F:17])([F:16])[F:15])[CH:9]=[CH:10][CH:11]=1
Reactant: COc1cccc(C(=O)Cl)c1
Reactant: FC(F)(F)C(F)(F)I
Solvent: ClCCl
Product: COc1cccc(C(=O)C(F)(F)C(F)(F)F)c1
Temperature: 0 °C
Reaction time: 5 h
Yield: 48.7 %

Procedure:
Under protective gas, 31.5 g (0.185 mol) of 3-methoxybenzoyl chloride in 150 ml of CH2Cl2 are initially introduced into a round-bottomed flask. 48.6 g (0.2 mol) of phosphorous acid trisdiethylamide are added at about -10° C. 50 g (0.2 mol) of pentafluoroethyl iodide are then introduced into the reaction mixture at 0° C. during the course of one hour. The mixture is stirred for a further 5 hours at 0° C. and then worked up analogously to Example 1. 22.9 g (61% yield) of 1-(3-methoxyphenyl)-2,2,3,3,3-pentafluoropropan-1-one of b.p. 95°-97° C./11 mbar are obtained.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[CH2:12][CH2:11][C:10]3[CH:13]=[C:14]([Cl:17])[CH:15]=[CH:16][C:9]=3[CH:8]([N:18]3[CH2:23][CH2:22][N:21]([C:24](=[O:43])[CH2:25][CH:26]4[CH2:31][CH2:30][N:29]([C:32](=[N:40][C:41]#[N:42])[O:33]C5C=CC=CC=5)[CH2:28][CH2:27]4)[CH2:20][CH2:19]3)[C:5]2=[N:6][CH:7]=1.[NH2:44][OH:45]>CO>[Br:1][C:2]1[CH:3]=[C:4]2[CH2:12][CH2:11][C:10]3[CH:13]=[C:14]([Cl:17])[CH:15]=[CH:16][C:9]=3[CH:8]([N:18]3[CH2:19][CH2:20][N:21]([C:24](=[O:43])[CH2:25][CH:26]4[CH2:27][CH2:28][N:29]([C:32]5[N:40]=[C:41]([NH2:42])[O:45][N:44]=5)[CH2:30][CH2:31]4)[CH2:22][CH2:23]3)[C:5]2=[N:6][CH:7]=1.[Br:1][C:2]1[CH:3]=[C:4]2[CH2:12][CH2:11][C:10]3[CH:13]=[C:14]([Cl:17])[CH:15]=[CH:16][C:9]=3[CH:8]([N:18]3[CH2:19][CH2:20][N:21]([C:24](=[O:43])[CH2:25][CH:26]4[CH2:27][CH2:28][N:29]([C:32]5[O:33][N:42]=[C:41]([NH2:44])[N:40]=5)[CH2:30][CH2:31]4)[CH2:22][CH2:23]3)[C:5]2=[N:6][CH:7]=1
Reactant: N#CN=C(Oc1ccccc1)N1CCC(CC(=O)N2CCN(C3c4ccc(Cl)cc4CCc4cc(Br)cnc43)CC2)CC1
Reactant: NO
Solvent: CO
Product: Nc1nc(N2CCC(CC(=O)N3CCN(C4c5ccc(Cl)cc5CCc5cc(Br)cnc54)CC3)CC2)no1
Product: Nc1noc(N2CCC(CC(=O)N3CCN(C4c5ccc(Cl)cc5CCc5cc(Br)cnc54)CC3)CC2)n1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
Phenyl 4-[2-[4-(3-bromo-8-chloro-6,11-dihydro-5H-benzo[5,6] cyclohepta[1,2-b]pyridin-11-yl)-1-piperazinyl]-2-oxoethyl]-N-cyano-1-piperidine-carboximidate (Step A of Example 8) (1 equivalent) is dissolved in methanol. Hydroxylamine (1 equivalent) is added and the mixture is stirred at 25° C. for 1h. The mixture is evaporated to dryness and chromatographed on silica gel to give the title compounds of Formulas 7.2 ((3-[4-[2-[4-(3-bromo-8-chloro-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-yl)-1-piperazinyl]-2-oxoethyl]-1-piperidinyl]-5-amino-1,2,4-oxadiazole) and 7.3 ((5-[4-[2-[4-(3-bromo-8-chloro-6,11-dihydro-5H-benzo[5,6]cyclohepta-[1,2-b]pyridin-11-yl)-1-piperazinyl]-2-oxoethyl]-1-piperidinyl]-3-amino-1,2,4-oxadiazole).
Reaction SMILES: [CH2:1]([NH2:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl[C:10]1[C:11]2[CH:23]=[C:22]([CH2:24][CH3:25])[S:21][C:12]=2[N:13]=[C:14]([C:16]2[O:20][N:19]=[CH:18][CH:17]=2)[N:15]=1>>[O:20]1[C:16]([C:14]2[N:15]=[C:10]([NH:8][CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)[C:11]3[CH:23]=[C:22]([CH2:24][CH3:25])[S:21][C:12]=3[N:13]=2)=[CH:17][CH:18]=[N:19]1
Reactant: NCc1ccccc1
Reactant: CCc1cc2c(Cl)nc(-c3ccno3)nc2s1
Product: CCc1cc2c(NCc3ccccc3)nc(-c3ccno3)nc2s1

Procedure:
With the procedure of Example 1, the reaction of benzylamine with 4-chloro-2-(isoxazol-5-yl)-6-ethyl-thieno-[2,3-d]-pyrimidine yields 2-(isoxazol-5-yl)-4-benzylamino-6-ethyl-thieno-[2,3-d]-pyrimidine.