Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH-].[K+].CS(O[CH2:8][CH:9]1[CH:14]([C:15]2[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=2)[CH2:13][O:12][C:10]1=[O:11])(=O)=O.[CH:23]1([SH:29])[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]1>C(O)C.C(OCC)C>[CH:23]1([S:29][CH2:8][CH:9]2[CH:14]([C:15]3[CH:16]=[CH:17][C:18]([O:21][CH3:22])=[CH:19][CH:20]=3)[CH2:13][O:12][C:10]2=[O:11])[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]1
Reactant: COc1ccc(C2COC(=O)C2COS(C)(=O)=O)cc1
Reactant: SC1CCCCC1
Agent: [K+]
Agent: [OH-]
Solvent: CCO
Solvent: CCOCC
Product: COc1ccc(C2COC(=O)C2CSC2CCCCC2)cc1
Reaction time: 4 h
Yield: 22 %

Procedure:
To a solution of 480 mg of potassium hydroxide in 40 ml of ethanol were added 2.0 g of α-methanesulfonyloxymethyl-β-(p-methoxyphenyl)-γ-butyrolactone and 1.6 ml of cyclohexylmercaptan and the resulting mixture was kept at room temperature for 4 hours. After completion of the reaction, the reaction mixture was diluted with 200 ml of ethyl ether, washed with water and saturated saline, dried over magnesium sulfate and the solvent was distilled off. The crude product thus obtained was purified by a silica gel column chromatography to give 600 mg (yield 22%) of the title compound.
Reaction SMILES: [F:1][CH:2]([F:28])[O:3][C:4]1[C:5]([C:14]([C:17]2[NH:21][C:20]3[CH:22]=[CH:23][C:24]([C:26]#[N:27])=[CH:25][C:19]=3[N:18]=2)([OH:16])[CH3:15])=[C:6]2[C:10](=[C:11]([CH3:13])[CH:12]=1)[NH:9][CH:8]=[CH:7]2.C1C(=O)N([Cl:36])C(=O)C1>CN(C=O)C>[Cl:36][C:7]1[C:6]2[C:10](=[C:11]([CH3:13])[CH:12]=[C:4]([O:3][CH:2]([F:1])[F:28])[C:5]=2[C:14]([C:17]2[NH:21][C:20]3[CH:22]=[CH:23][C:24]([C:26]#[N:27])=[CH:25][C:19]=3[N:18]=2)([OH:16])[CH3:15])[NH:9][CH:8]=1
Reactant: Cc1cc(OC(F)F)c(C(C)(O)c2nc3cc(C#N)ccc3[nH]2)c2cc[nH]c12
Reactant: O=C1CCC(=O)N1Cl
Solvent: CN(C)C=O
Product: Cc1cc(OC(F)F)c(C(C)(O)c2nc3cc(C#N)ccc3[nH]2)c2c(Cl)c[nH]c12
Temperature: 25 °C

Procedure:
To a solution of (+)-2-(1-(5-(difluoromethoxy)-7-methyl-1H-indol-4-yl)-1-hydroxyethyl)-1H-benzo[d]imidazole-5-carbonitrile (32 mg, 0.083 mmol) in DMF (0.83 mL) was added NCS (17 mg, 0.12 mmol) at 0° C., and the reaction was warmed to room temperature. After 2 hours the reaction was quenched with sat. aq. Na2S2O3 and extracted with EtOAc. The organic extract was dried over MgSO4, filtered and concentrated. The resulting residue was purified by flash chromatography (0-100% EtOAc in heptanes) to provide the title compound. 1H NMR (400 MHz, DMSO-d6) δ ppm 12.51-12.66 (m, 1H) 11.56 (br. s., 1H) 8.04 (m) 7.79-7.83 (m) 7.64-7.70 (m) 7.44-7.56 (m) 6.83-6.89 (m) 6.75 (s, 1H) 6.64-6.70 (m) 6.46-6.51 (m) 6.07-6.20 (m, 1H) 2.45 (s, 3H) 2.18 (s, 3H). HRMS calcd. for C20H15ClF2N4O2 (M+H)+ 417.0925. found 417.0942.
Reaction SMILES: [F:1][C:2]1([F:19])[O:7][C:6]2[CH:8]=[CH:9][C:10](C(C(C)C)=O)=[CH:11][C:5]=2[C:4]([F:18])([F:17])[O:3]1.[Cl:20]C(Cl)(Cl)C1C=C(Cl)C=CC=1OC(F)=O.F>>[F:1][C:2]1([F:19])[O:7][C:6]2[CH:8]=[CH:9][C:10]([Cl:20])=[CH:11][C:5]=2[C:4]([F:18])([F:17])[O:3]1
Reactant: O=C(F)Oc1ccc(Cl)cc1C(Cl)(Cl)Cl
Reactant: CC(C)C(=O)c1ccc2c(c1)C(F)(F)OC(F)(F)O2
Agent: F
Product: FC1(F)Oc2ccc(Cl)cc2C(F)(F)O1

Procedure:
For the preparation of a ketone such as isopropyl 2,2,4,4-tetrafluoro-1,3-benzodioxan-6-yl ketone, the procedure disclosed in U.S. Pat. No. 3,632,820 (Jan. 4, 1972), Example 6, is used to prepare the intermediate halobenzodioxane. According to that reference, fluoroformic acid 2-trichloromethyl-4-chlorophenyl ester is allowed to react with anhydrous hydrofluoric acid to yield 2,2,4,4-tetrafluoro-6-chloro-1,3-benzodioxane. This compound can then be utilized to prepare the isopropyl 2,2,4,4-tetrafluoro-1,3-benzodioxan-6-yl or related alkyl or aryl ketones by any of the methods set forth above for the other ketones.
Reaction SMILES: Cl[C:2]1[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][N:5]=[C:4]([NH:12][C:13]2[CH:18]=[CH:17][C:16]([CH:19]3[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:21][CH2:20]3)=[CH:15][C:14]=2[O:32][CH3:33])[N:3]=1.[C:34]([C:36]1[CH:37]=[C:38]([CH:42]=[CH:43][CH:44]=1)[C:39]([NH2:41])=[O:40])#[CH:35].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(N(CC)CC)C>CN(C=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[C:39]([C:38]1[CH:37]=[C:36]([C:34]#[C:35][C:2]2[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][N:5]=[C:4]([NH:12][C:13]3[CH:18]=[CH:17][C:16]([CH:19]4[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:21][CH2:20]4)=[CH:15][C:14]=3[O:32][CH3:33])[N:3]=2)[CH:44]=[CH:43][CH:42]=1)(=[O:40])[NH2:41]
Reactant: C#Cc1cccc(C(N)=O)c1
Reactant: COc1cc(C2CCN(C(=O)OC(C)(C)C)CC2)ccc1Nc1ncc(C(F)(F)F)c(Cl)n1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Cu]I
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: COc1cc(C2CCN(C(=O)OC(C)(C)C)CC2)ccc1Nc1ncc(C(F)(F)F)c(C#Cc2cccc(C(N)=O)c2)n1
Temperature: 120 °C
Reaction time: 8 h
Yield: 61.3 %

Procedure:
To a mixture of tert-butyl 4-(4-((4-chloro-5-(trifluoromethyl)pyrimidin-2-yl)amino)-3-methoxyphenyl)piperidine-1-carboxylate (I34) (0.098 g, 0.20 mmol), 3-ethynylbenzamide (I31) (0.038 g, 0.26 mmol), PdCl2(PPh3)2 (9 mg, 0.01 mmol), triphenylphosphine (0.010 g, 0.04 mmol) and copper(I) iodide (0.009 g, 0.05 mmol) in DMF (2 mL), that had been degassed with nitrogen for 10 minutes, was added triethylamine (0.090 mL, 0.65 mmol). The mixture was degassed with nitrogen then heated to 120° C. for 25 minutes under microwave irradiation. On cooling to room temperature the resulting mixture was left overnight, then an additional portion of 3-ethynylbenzamide (I26) (0.047 g, 0.32 mmol) was added. After degassing with nitrogen the reaction was heated at 120° C. for 25 minutes under microwave irradiation. The volatiles were evaporated under reduced pressure and the residue purified using silica gel column chromatography (20-70% EtOAc/petroleum benzine 40-60° C.) to give the title compound (I35) (0.073 g, 61%) as a yellow solid; 1H NMR (400 MHz, CDCl3) δ 8.66 (s, 1H), 8.35 (d, J=8.3 Hz, 1H), 8.04 (dd, J=1.4, 1.4 Hz, 1H), 8.02 (s, 1H), 7.93 (ddd, J=7.9, 1.8, 1.2 Hz, 1H), 7.80 (m, 1H), 7.53 (m, 1H), 6.88 (dd, J=8.3, 1.6 Hz, 1H), 6.76 (d, J=1.8 Hz, 1H), 4.27 (m, 2H), 3.91 (s, 3H), 2.81 (m, J=12.2 Hz, 2H), 2.64 (tt, J=12.2, 3.4 Hz, 1H), 1.84 (m, 2H), 1.65 (m, 2H), 1.49 (s, 9H). LCMS Method C: rt 6.59 min; m/z 496.1 [(M-Boc)+H]+, 540.0 [(M-t-Bu)+H]+.
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH2:14][CH2:13][CH2:12][C@H:11]([NH:15][C@@H:16]3[CH2:21][CH2:20][CH2:19][CH2:18][C@H:17]3[NH:22][C:23](=[O:35])CC3C4C(=CC=CC=4)N(C)C=3)[CH2:10]2)=[CH:5][CH:4]=1)#[N:2].C(Cl)(=O)[O:37][CH2:38][C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][C:40]=1[Cl:45]>>[C:1]([C:3]1[CH:4]=[CH:5][C:6]([N:9]2[CH2:14][CH2:13][CH2:12][C@H:11]([NH:15][C@@H:16]3[CH2:21][CH2:20][CH2:19][CH2:18][C@H:17]3[NH:22][C:23](=[O:35])[O:37][CH2:38][C:39]3[CH:44]=[CH:43][CH:42]=[CH:41][C:40]=3[Cl:45])[CH2:10]2)=[CH:7][CH:8]=1)#[N:2]
Reactant: O=C(Cl)OCc1ccccc1Cl
Reactant: Cn1cc(CC(=O)N[C@@H]2CCCC[C@H]2N[C@H]2CCCN(c3ccc(C#N)cc3)C2)c2ccccc21
Product: N#Cc1ccc(N2CCC[C@H](N[C@@H]3CCCC[C@H]3NC(=O)OCc3ccccc3Cl)C2)cc1

Procedure:
2-Chlorobenzyl (1R,2R)-2-((S)-1-(4-cyanophenyl)piperidin-3-ylamino)cyclohexylcarbamate was synthesized using 4-((S)-3-((1R,2R)-2-aminocyclohexylamino)piperidin-1-yl)benzonitrile (from intermediate D, Example 10) (60 mg, 0.2 mmol) and 2-chlorobenzyl carbonochloridate (68 mg, 0.22 mmol) according to General Procedure H to give 20 mg (21.3%) of pale yellow solid. Anal. Calcd. for C26H31ClN4O2 m/z 466.2, found: 467.2 (M+H)+; 1H NMR (400 MHz, CD3OD) δ ppm 7.44 (d, J=8.7 Hz, 2H), 7.38 (m, 2H), 7.29 (m, 2H), 6.98 (d, J=9 Hz, 2H), 5.1 (s, 2H), 3.69 (m, 1H), 3.56 (m, 1H), 3.29 (m, 1H), 3.02 (m, 1H), 2.79 (d, J=8.4 Hz, 2H), 2.54 (m, 1H), 2.05 (m, 1H), 1.92 (m, 2H), 1.79 (m, 3H), 1.64 (m, 1H), 1.34 (m, 5H), 1.22 (m, 1H).
Reaction SMILES: C([NH:9][C:10]([NH:12][C:13]1[S:14][CH:15]=[C:16]([CH:18]([C:20]2[CH:25]=[CH:24][C:23]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)=[C:22]([F:32])[CH:21]=2)[CH3:19])[N:17]=1)=[S:11])(=O)C1C=CC=CC=1.CC(C)=O.CO.C(=O)([O-])[O-].[K+].[K+]>O>[F:32][C:22]1[CH:21]=[C:20]([CH:18]([C:16]2[N:17]=[C:13]([NH:12][C:10]([NH2:9])=[S:11])[S:14][CH:15]=2)[CH3:19])[CH:25]=[CH:24][C:23]=1[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1
Reactant: CC(c1ccc(-c2ccccc2)c(F)c1)c1csc(NC(=S)NC(=O)c2ccccc2)n1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Solvent: O
Solvent: CO
Product: CC(c1ccc(-c2ccccc2)c(F)c1)c1csc(NC(N)=S)n1
Yield: 85.8 %

Procedure:
To N-benzoyl-N'-(4-(1-(2-fluoro-4-biphenylyl)ethyl)thiazol-2-yl)thiourea (0.25 g, 0.561 mmol) in mixture of acetone (10 ml) and methanol (2.5 ml) was added potassium carbonate (0.05 g) in water (1 ml). After the mixture was refluxed for 5 h, the mixture was extracted with ethyl acetate. The extracts were washed with water, dried over, and evaporated under reduced pressure to residue, which was chromatographed and recrystallized with mixture of chloroform and n-hexane to afford N-(4-(1-(2-fluoro-4-biphenylyl)ethyl)thiazol-2-yl)thiourea (0.172 g, 82% yield) as crystalline material: 192.0°-194.0° C.
Reaction SMILES: O1[C:5]2([CH2:10][CH2:9][CH:8]([C:11]3[N:12]=[CH:13][C:14]([NH2:17])=[N:15][CH:16]=3)[CH2:7][CH2:6]2)[O:4]CC1.C(#N)C.Cl.[OH-].[Na+]>C(OCC)(=O)C.O>[NH2:17][C:14]1[N:15]=[CH:16][C:11]([CH:8]2[CH2:7][CH2:6][C:5](=[O:4])[CH2:10][CH2:9]2)=[N:12][CH:13]=1
Reactant: Nc1cnc(C2CCC3(CC2)OCCO3)cn1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCOC(C)=O
Solvent: O
Solvent: CC#N
Product: Nc1cnc(C2CCC(=O)CC2)cn1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 79.6 %

Procedure:
To 5-(1,4-dioxaspiro[4.5]decan-8-yl)pyrazin-2-amine (8.68 g, 45.4 mmol) was added acetonitrile (368 mL), water (245 mL) and 3M HCl (76 mL). The reaction was stirred at room temperature for 30 min. The reaction was basified with excess 1M NaOH, and then diluted with of ethyl acetate. The organic layer was separated. The aqueous layer was extracted well with EtOAc/2-methyl THF (1:1) three times. Organic layers were combined and dried over Na2SO4, filtered and concentrated to give 6.91 g of product as free base. LCMS (m/z): 192.12 (MH+), 0.30 min.
Reaction SMILES: C(O[C:4](=[O:20])[CH2:5][CH2:6][P:7]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)C.[CH3:21][NH:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH3:40].C[O-].[Na+]>>[CH3:21][N:22]([CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH3:40])[C:4](=[O:20])[CH2:5][CH2:6][P:7]([C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1)[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1
Reactant: CCCCCCCCCCCCCCCCCCNC
Reactant: CCOC(=O)CCP(c1ccccc1)c1ccccc1
Agent: C[O-]
Agent: [Na+]
Product: CCCCCCCCCCCCCCCCCCN(C)C(=O)CCP(c1ccccc1)c1ccccc1
Temperature: 100 °C

Procedure:
A mixture of 5.7 g ethyl-3-diphenylphosphinopropionate (9.9 mmoles), 5.1 g N-methyl-n-octadecylamine (18.0 mmoles), and 0.3 g sodium methoxide (5.6 mmoles) were first deoxygenated and then heated to 100° C. under a nitrogen atmosphere for 24 hours. The mixture was then cooled and extracted with pentane. The pentane soluble was rotovapped to an oil.
Reaction SMILES: [CH:1]([N:4]1[C:8]([C:9]2[N:18]=[C:17]3[N:11]([CH2:12][CH2:13][O:14][C:15]4[CH:22]=[C:21]([O:23][C:24]([CH3:37])([CH2:31]OS(C)(=O)=O)[CH2:25]OS(C)(=O)=O)[CH:20]=[CH:19][C:16]=43)[CH:10]=2)=[N:7][C:6]([CH3:38])=[N:5]1)([CH3:3])[CH3:2]>C(N)C1C=CC=CC=1>[CH2:17]([N:11]1[CH2:25][C:24]([CH3:37])([O:23][C:21]2[CH:20]=[CH:19][C:16]3[C:17]4[N:11]([CH2:12][CH2:13][O:14][C:15]=3[CH:22]=2)[CH:10]=[C:9]([C:8]2[N:4]([CH:1]([CH3:2])[CH3:3])[N:5]=[C:6]([CH3:38])[N:7]=2)[N:18]=4)[CH2:31]1)[C:16]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:15]=1
Reactant: Cc1nc(-c2cn3c(n2)-c2ccc(OC(C)(COS(C)(=O)=O)COS(C)(=O)=O)cc2OCC3)n(C(C)C)n1
Solvent: NCc1ccccc1
Product: Cc1nc(-c2cn3c(n2)-c2ccc(OC4(C)CN(Cc5ccccc5)C4)cc2OCC3)n(C(C)C)n1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
A solution of methanesulfonic acid 2-[2-(2-isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulen-8-yloxy]-3-methanesulfonyloxy-2-methylpropyl ester (0.096 mmol) in benzylamine (0.5 mL) was heated at 150° C. for 1 h and then 180° C. for a further 1 h using microwave irradiation. After cooling to RT, the crude reaction mixture was purified by column chromatography (C18, gradient 15-55% MeOH in 0.5% TFA/H2O) and then loaded onto an Isolute® SCX-2 cartridge. The cartridge was washed with MeOH and the product eluted with 0.5M NH3/MeOH affording the title compound as a colourless gum (31 mg, 67% over two steps). LCMS (Method B): RT 2.40 min [M+H]+ 485
Reaction SMILES: CCN(C(C)C)C(C)C.Cl.[NH2:11][C@H:12]([C:16]([N:18]1[CH2:26][C@H:25]([O:27][C:28]2[C:37]3[C:32](=[CH:33][CH:34]=[C:35]([CH:38]=[CH2:39])[CH:36]=3)[CH:31]=[CH:30][N:29]=2)[CH2:24][C@H:19]1[C:20]([O:22][CH3:23])=[O:21])=[O:17])[CH:13]([CH3:15])[CH3:14].C([N:57]=[C:58]=[S:59])(OCC1C2C(=CC=CC=2)C2C1=CC=CC=2)=O.N1CCCCC1>C(Cl)Cl.CO>[NH2:57][C:58]([NH:11][C@H:12]([C:16]([N:18]1[CH2:26][C@H:25]([O:27][C:28]2[C:37]3[C:32](=[CH:33][CH:34]=[C:35]([CH:38]=[CH2:39])[CH:36]=3)[CH:31]=[CH:30][N:29]=2)[CH2:24][C@H:19]1[C:20]([O:22][CH3:23])=[O:21])=[O:17])[CH:13]([CH3:15])[CH3:14])=[S:59]
Reactant: O=C(N=C=S)OCC1c2ccccc2-c2ccccc21
Reactant: C=Cc1ccc2ccnc(O[C@@H]3C[C@@H](C(=O)OC)N(C(=O)[C@@H](N)C(C)C)C3)c2c1
Agent: Cl
Solvent: C1CCNCC1
Solvent: ClCCl
Solvent: CO
Product: C=Cc1ccc2ccnc(O[C@@H]3C[C@@H](C(=O)OC)N(C(=O)[C@@H](NC(N)=S)C(C)C)C3)c2c1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
iPr2NEt (2 eq) was added to a suspension of hydrochloride from Step 2 in DCM at 0° C., and the resulting clear solution was immediately added to a solution of FMOC-isothiocyanate (1.1 eq) in DCM at 0° C. The resulting mixture was stirred at RT for 30 min and then treated with a 20% solution of piperidine in MeOH. After 3 h, the volatiles were removed under reduced pressure and the residue was purified by SiO2 gel chromatography (gradient elution, hexane/EtOAc=8/2 to DCM/MeOH=95/5) to give the title compound as a pale yellow foam. MS (ES+) C23H28N4O4S requires: 456. Found: 457 (M+H+).
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:13])[C:5](Br)([CH2:9][CH2:10][CH3:11])[CH2:6][CH2:7][CH3:8])[CH3:2]>C(#N)C>[CH2:1]([O:3][C:4](=[O:13])[C:5]([CH2:9][CH2:10][CH3:11])=[CH:6][CH2:7][CH3:8])[CH3:2]
Reactant: CCCC(Br)(CCC)C(=O)OCC
Solvent: CC#N
Product: CCC=C(CCC)C(=O)OCC

Procedure:
A solution of 100 g of triethylene diamine (1,4-diazabicyclo[2,2,2]-octane) in 400 ml of acetonitrile are added to a solution of 100 g of 2-bromo-2-propyl pentanoic acid ethyl ester in 200 ml of acetonitrile. The colourless reaction mixture is refluxed for 8 hours and precipitation of a white salt starts after only 15 minutes. Subsequently approximately 450 ml of acetonitrile are distilled off and recovered on the rotary evaporator at 200 mbar and 40° C. The oily-crystalline residue is mixed with 1000 ml of water, accompanied by the dissolving of the separated salt. After acidifying with 1N hydrochloric acid to pH 1, the separated oil is taken up in 150 ml of n-hexane and the aqueous phase is extracted twice more with in each case 150 ml of n-hexane. After washing and drying the organic phase, distillation takes place. The yield is 54.3 g of a mixture of E and Z-2-propyl-2-pentenoic acid ethyl ester with a content of 42 g of the sought E-isomer, corresponding to 62% based on the starting product.
Reaction SMILES: [CH3:1][N:2]1[C:10]2[C:5](=[CH:6][C:7]([O:20][CH3:21])=[C:8]([O:11][CH2:12][CH2:13][N:14]3[CH2:19][CH2:18][O:17][CH2:16][CH2:15]3)[CH:9]=2)[C:4]([C:22]2[N:30](S(C3C=CC(C)=CC=3)(=O)=O)[C:25]3=[N:26][CH:27]=[CH:28][CH:29]=[C:24]3[CH:23]=2)=[CH:3]1.[OH-].[K+]>>[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][C:7]([O:20][CH3:21])=[C:8]([O:11][CH2:12][CH2:13][N:14]3[CH2:19][CH2:18][O:17][CH2:16][CH2:15]3)[CH:9]=2)[C:4]([C:22]2[NH:30][C:25]3=[N:26][CH:27]=[CH:28][CH:29]=[C:24]3[CH:23]=2)=[CH:3]1
Reactant: COc1cc2c(-c3cc4cccnc4n3S(=O)(=O)c3ccc(C)cc3)cn(C)c2cc1OCCN1CCOCC1
Agent: [K+]
Agent: [OH-]
Product: COc1cc2c(-c3cc4cccnc4[nH]3)cn(C)c2cc1OCCN1CCOCC1
Yield: 66.7 %

Procedure:
2-[1-Methyl-5-methoxy-6-(2-morpholin-4-yl-ethoxy)-1H-indol-3-yl]-1H-pyrrolo[2,3-b]pyridine is prepared by following the procedure described in example 89a, but using 0.24 g of 2-[1-methyl-5-methoxy-6-(2-morpholin-4-ylethoxy)-1H-indol-3-yl]-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine and 1.93 ml of a 5N aqueous potassium hydroxide solution. 0.116 g of 2-[1-methyl-5-methoxy-6-(2-morpholin-4-ylethoxy)-1H-indol-3-yl]-1H-pyrrolo[2,3-b]pyridine is obtained, the characteristics of which are as follows:
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:14](=[CH:15][C:16]=1[O:17][CH3:18])[C@H:13]1[C@H:8]([CH2:9][CH2:10][CH2:11][CH2:12]1)[N:7]=[C:6]2[C:19]1[CH:24]=[CH:23][C:22]([S:25]([CH3:28])(=[O:27])=[O:26])=[CH:21][CH:20]=1.ClC1C=CC=C(C(OO)=[O:37])C=1>ClCCl>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:14](=[CH:15][C:16]=1[O:17][CH3:18])[C@H:13]1[C@H:8]([CH2:9][CH2:10][CH2:11][CH2:12]1)[N+:7]([O-:37])=[C:6]2[C:19]1[CH:20]=[CH:21][C:22]([S:25]([CH3:28])(=[O:27])=[O:26])=[CH:23][CH:24]=1
Reactant: COc1cc2c(cc1OC)[C@@H]1CCCC[C@@H]1N=C2c1ccc(S(C)(=O)=O)cc1
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: ClCCl
Product: COc1cc2c(cc1OC)[C@@H]1CCCC[C@@H]1[N+]([O-])=C2c1ccc(S(C)(=O)=O)cc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
500 mg of (−)-cis-8,9-dimethoxy-6-(4-methanesulfonylphenyl)-1,2,3,4,4a,10b-hexahydrophenanthridine are dissolved in 30 ml of dichloromethane, treated with 340 mg of m-chloroperbenzoic acid with ice-cooling and stirred in an ice bath for 3 h and at RT for 1 h. After removing the solvent under reduced pressure and chromatography on silica gel using ethyl acetate/triethylamine in the ratio 7:1, the title compound is obtained by concentrating the product fractions.
Reaction SMILES: [C:1](Cl)(=O)C(Cl)=O.[F:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[CH:22]=[C:21]([N+:23]([O-:25])=[O:24])[CH:20]=[CH:19][C:15]=2[C:16]([OH:18])=[O:17])=[CH:10][CH:9]=1.CO>C(Cl)Cl.CN(C=O)C.CN(C1C=CN=CC=1)C>[F:7][C:8]1[CH:9]=[CH:10][C:11]([C:14]2[CH:22]=[C:21]([N+:23]([O-:25])=[O:24])[CH:20]=[CH:19][C:15]=2[C:16]([O:18][CH3:1])=[O:17])=[CH:12][CH:13]=1
Reactant: O=C(O)c1ccc([N+](=O)[O-])cc1-c1ccc(F)cc1
Reactant: O=C(Cl)C(=O)Cl
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Solvent: CO
Solvent: CN(C)C=O
Product: COC(=O)c1ccc([N+](=O)[O-])cc1-c1ccc(F)cc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 95.4 %

Procedure:
Oxalyl chloride (9.35 g; 0.074 mol) was added to a solution of 2-(4-fluorophenyl)-4-nitrobenzoic acid (17.5 g; 0.067 mol) in methylene chloride (150 ml). After addition of DMF (3 drops), the mixture was stirred at ambient temperature for 2 hours. After evaporation to dryness the residue was redissolved in methylene chloride (100 ml); methanol (50 ml) and DMAP (8.2 g; 0.067 mol) was added at 0° C. After stirring at ambient temperature for 2 hours, the mixture was evaporated to dryness. The residue was taken up in methylene chloride washed with a 2N HCl, saturated aqueous sodium bicarbonate and evaporated to give methyl 2-(4-fluorophenyl)-4-nitrobenzoate (17.6 g; 95%).
Reaction SMILES: C(O)CCC#C.ClC1C(Cl)=CC=CC=1I.[Cl:16][C:17]1[C:22]([Cl:23])=[CH:21][CH:20]=[CH:19][C:18]=1[C:24]#[C:25][CH2:26][CH2:27][CH:28]=[O:29]>>[Cl:16][C:17]1[C:22]([Cl:23])=[CH:21][CH:20]=[CH:19][C:18]=1[C:24]#[C:25][CH2:26][CH2:27][CH2:28][OH:29]
Reactant: O=CCCC#Cc1cccc(Cl)c1Cl
Agent: C#CCCCO
Agent: Clc1cccc(I)c1Cl
Product: OCCCC#Cc1cccc(Cl)c1Cl

Procedure:
5-(2',3'-dichlorophenyl)-4-pentyn-1-ol was prepared from 4-pentyn-1-ol and 2,3-dichloro-iodobenzene using the same method as in Example 15 and converted into 5-(2',3'-dichlorophenyl)-4-pentyn-1-al as in Example 9.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:9]=[CH:10][C:11]3[NH:16][C:15](=O)[O:14][CH:13]([CH3:18])[C:12]=3[CH:19]=2)[CH:5]=[CH:6][CH:7]=1.COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:29])=CC=1>C1(C)C=CC=CC=1>[F:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:9]=[CH:10][C:11]3[NH:16][C:15](=[S:29])[O:14][CH:13]([CH3:18])[C:12]=3[CH:19]=2)[CH:5]=[CH:6][CH:7]=1
Reactant: COc1ccc(P2(=S)SP(=S)(c3ccc(OC)cc3)S2)cc1
Reactant: CC1OC(=O)Nc2ccc(-c3cccc(F)c3)cc21
Solvent: Cc1ccccc1
Product: CC1OC(=S)Nc2ccc(-c3cccc(F)c3)cc21

Procedure:
A solution of 6-(3-fluorophenyl)-4-methyl-1,4-dihydro-2H-3,1-benzoxazin-2-one (0.15 g, 0.58 mmol) in toluene was treated with Lawesson's reagent according to the procedure in example 9 to yield 6-(3-fluorophenyl)-4-methyl-1,4-dihydro-2H-3,1-benzoxazin-2-thione (0.08 g, 50%) as an off-white solid (0.08 g, 50%): mp 173-174° C.; 1H-NMR (DMSO-d6) δ 12.27 (s, 1H), 7.70 (dd, 1H, J=8.2, 2.0 Hz), 7.62 (s, 1H), 7.46-7.56 (m, 3H), 7.15-7.22 (m, 1H), 7.11 (d, 1H, J=8.3 Hz), 5.64 (q, 1H, J=6.6 Hz), 1.67 (d, 3H, J=6.6 Hz); MS (ESI) m/z 272 [M−H]−.
Reaction SMILES: [Cl:1][C:2]([Cl:12])=[CH:3][C@@H:4]1[C@H:6]([C:7]([OH:9])=[O:8])[C:5]1([CH3:11])[CH3:10].C(Cl)(=O)C(Cl)=O.N1C=CC=CC=1.[Br:25][C:26]1[O:27][C:28]([C:31]2[CH:32]=[C:33]([CH2:37]O)[CH:34]=[CH:35][CH:36]=2)=[CH:29][CH:30]=1>C1(C)C=CC=CC=1.CCCCCC.C(OCC)(=O)C>[Cl:1][C:2]([Cl:12])=[CH:3][C@@H:4]1[C@H:6]([C:7]([O:9][CH2:37][C:33]2[CH:34]=[CH:35][CH:36]=[C:31]([C:28]3[O:27][C:26]([Br:25])=[CH:30][CH:29]=3)[CH:32]=2)=[O:8])[C:5]1([CH3:10])[CH3:11]
Reactant: OCc1cccc(-c2ccc(Br)o2)c1
Reactant: CC1(C)[C@H](C=C(Cl)Cl)[C@@H]1C(=O)O
Agent: O=C(Cl)C(=O)Cl
Solvent: c1ccncc1
Solvent: CCOC(C)=O
Solvent: CCCCCC
Product: CC1(C)[C@H](C=C(Cl)Cl)[C@@H]1C(=O)OCc1cccc(-c2ccc(Br)o2)c1
Temperature: 25 °C
Reaction time: 2 h
Yield: 33.8 %

Procedure:
Under a dry nitrogen atmosphere, a stirred solution of 1.2 g (0.006 mol) of cis-3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropanecarboxylic acid in 40 mL of toluene was heated to 80° C.±5° C. To this solution was added a solution of 0.7 g (0.006 mol) of oxalyl chloride in 5 mL of toluene. Upon complete addition, the reaction mixture was heated at 82° C.±5° C. for 60 hours. The reaction mixture was cooled to ambient temperature, and 0.9 g (0.011 mol) of pyridine was added. The reaction mixture was stirred for two hours, then warmed to 70° and 1.4 g (0.006 mol) of 3-(2-bromo-5-furanyl)phenylmethanol in 10 mL of toluene was added. Upon complete addition, the reaction mixture was stirred at 70° C.±5° C. for 21.5 hours. The reaction mixture was transferred to a separatory funnel, 200 mL of toluene washings were added, and the mixture was washed with 100 mL of an aqueous 2 N hydrochloric acid solution, 100 mL of a saturated aqueous solution of sodium chloride, 100 mL of an aqueous 2 N solution of sodium hydroxide, and finally 100 mL of a saturated aqueous solution of sodium chloride. The organic layer was dried with magnesium sulfate, filtered, and the filtrate concentrated under reduced pressure to give a residual oil. The oil was subjected to medium pressure liquid chromatography using hexane:ethyl acetate (46:1). The appropriate fractions were combined and concentrated to give a crystalline solid. The solid was recrystallized from methanol, then from hexane to give 0.9 g of [3-(5-bromofuranyl)phenyl]methyl cis-3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropanecarboxylate, m.p. 76.5°-77° C.