Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[CH:3]=[N:4][N:5]([CH3:19])[C:6]=1[C:7]1[CH:8]=[C:9]([C:15]([O:17][CH3:18])=[O:16])[S:10][C:11]=1[CH2:12][CH2:13][CH3:14].[C:20](=O)([O-])[O-].[K+].[K+].CB1OB(C)OB(C)O1>CN(C)C=O>[CH3:19][N:5]1[C:6]([C:7]2[CH:8]=[C:9]([C:15]([O:17][CH3:18])=[O:16])[S:10][C:11]=2[CH2:12][CH2:13][CH3:14])=[C:2]([CH3:20])[CH:3]=[N:4]1
Reactant: CCCc1sc(C(=O)OC)cc1-c1c(Br)cnn1C
Reactant: O=C([O-])[O-]
Agent: CB1OB(C)OB(C)O1
Agent: [K+]
Solvent: CN(C)C=O
Product: CCCc1sc(C(=O)OC)cc1-c1c(C)cnn1C
Yield: 84.5 %

Procedure:
A solution of methyl 4-(4-bromo-1-methyl-1H-pyrazol-5-yl)-5-propyl-2-thiophenecarboxylate (242 mg, 0.71 mmol) PdCl2(dppf) (52 mg, 0.07 mmol), potassium carbonate (487 mg, 3.53 mmol) and trimethylboroxine (0.20 ml, 1.41 mmol) in N,N-Dimethylformamide (3.5 ml) was stirred at 110° C. in a sealed tube for 2 h. The reaction mixture was partitioned between H2O-DCM and the aqueous phase was washed several times with DCM. The combined organic fractions were dried over Na2SO4, concentrated and purified via column chromatography (10-50% EtOAc in hexanes) affording methyl 4-(1,4-dimethyl-1H-pyrazol-5-yl)-5-propyl-2-thiophenecarboxylate (184 mg, 0.60 mmol, 84% yield) as a yellow oil: LCMS (ES) m/z=279 (M+H)+.
Reaction SMILES: [Li+].[BH4-].C[O:4][C:5](=O)[C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([CH3:12])[C:7]=1[O:13][CH3:14].CO>CCOCC>[CH3:14][O:13][C:7]1[C:8]([CH3:12])=[CH:9][CH:10]=[CH:11][C:6]=1[CH2:5][OH:4]
Reactant: COC(=O)c1cccc(C)c1OC
Agent: [BH4-]
Agent: [Li+]
Solvent: CO
Solvent: CCOCC
Product: COc1c(C)cccc1CO
Reaction time: 0.08 h

Procedure:
LiBH4 (5.10 g, 0.23 mmol) was added to a solution of 2-methoxy-3-methyl-benzoic acid methyl ester (8.46 g, 47.00 mmol) in Et2O at 0° C. The reaction mixture was stirred for 5 minutes, MeOH (9.50 mL, 0.23 mmol) was added in a dropwise fashion. The reaction mixture was then stirred for 30 minutes, and was quenched into 1N NaOH. The resulting solution was extracted with Et2O (3×200 mL) and the combined organic phases were washed with brine (1×150 mL), dried over MgSO4 and concentrated to afford the title compound.
Reaction SMILES: [F:1][CH2:2][CH2:3][N:4]1[C:8]2[CH:9]=[CH:10][C:11]([N+:13]([O-])=O)=[CH:12][C:7]=2[CH2:6][S:5]1(=[O:17])=[O:16].CCOC(C)=O>[Pd]>[NH2:13][C:11]1[CH:10]=[CH:9][C:8]2[N:4]([CH2:3][CH2:2][F:1])[S:5](=[O:17])(=[O:16])[CH2:6][C:7]=2[CH:12]=1
Reactant: O=[N+]([O-])c1ccc2c(c1)CS(=O)(=O)N2CCF
Agent: [Pd]
Solvent: CCOC(C)=O
Product: Nc1ccc2c(c1)CS(=O)(=O)N2CCF
Reaction time: 4 h
Yield: 99.5 %

Procedure:
The product of Step 1 (1.25 g, 4.8 mmol) is dissolved into EtOAc (30 mL) in a Parr bottle and 10% Pd/C (100 mg) added under nitrogen. The mixture is hydrogenated on a Parr apparatus for 4 hrs at 40 psi. Filtration and evaporation of solvent gave a solid (1.1 g, 99%). Mp 119-21° C. HRMS (FAB) calcd for C9H11FN2O2S +H1 231.0603, found 231.0610.
Reaction SMILES: [C:1](Cl)(=[O:3])[CH3:2].[Sn](Cl)(Cl)(Cl)Cl.[N:10]1([N:15]2[C:23](=[O:24])[C:22]3[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=3)[C:16]2=[O:25])[CH:14]=[CH:13][CH:12]=[CH:11]1>C(Cl)Cl>[C:1]([C:11]1[N:10]([N:15]2[C:23](=[O:24])[C:22]3[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=3)[C:16]2=[O:25])[CH:14]=[CH:13][CH:12]=1)(=[O:3])[CH3:2]
Reactant: O=C1c2ccccc2C(=O)N1n1cccc1
Reactant: CC(=O)Cl
Agent: Cl[Sn](Cl)(Cl)Cl
Solvent: ClCCl
Product: CC(=O)c1cccn1N1C(=O)c2ccccc2C1=O
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
To a stirred solution of acetyl chloride (6.77 ml) in DCM (400 ml) was added tin (IV) chloride (11.14 ml) at -5° C., under nitrogen. 2-(1H-pyrrol-1-yl)-1H-isoindole-1,3(2H)dione (20.0 g) was then added portion-wise, keeping the temperature below 0° C. The reaction mixture was then stirred at 0° C. for 0.5 hour, at which time it was poured into ice water. The layers were separated and the aqueous phase was extracted with DCM. The combined organics were washed twice with 5% HCl (aq.) and dried (MgSO4). Filtration and concentration gave the etude product. Purification via flash column chromatography (silica gel, DCM) afforded 9.62 g of the product as a solid, m.p. 204°-205° C.
Reaction SMILES: [Cl:1][C:2]1[CH:28]=[CH:27][C:5]2[CH:6]([CH:15]3[CH2:20][CH2:19][N:18]([C:21](SC)=[N:22][C:23]#[N:24])[CH2:17][CH2:16]3)[C:7]3[C:12]([CH2:13][S:14][C:4]=2[CH:3]=1)=[CH:11][CH:10]=[CH:9][N:8]=3.[O:29]1[C:33]2[CH:34]=[CH:35][C:36]([CH2:38][NH2:39])=[CH:37][C:32]=2[O:31][CH2:30]1>>[O:29]1[C:33]2[CH:34]=[CH:35][C:36]([CH2:38][NH:39][C:21]([N:18]3[CH2:19][CH2:20][CH:15]([CH:6]4[C:7]5=[N:8][CH:9]=[CH:10][CH:11]=[C:12]5[CH2:13][S:14][C:4]5[CH:3]=[C:2]([Cl:1])[CH:28]=[CH:27][C:5]4=5)[CH2:16][CH2:17]3)=[N:22][C:23]#[N:24])=[CH:37][C:32]=2[O:31][CH2:30]1
Reactant: NCc1ccc2c(c1)OCO2
Reactant: CSC(=NC#N)N1CCC(C2c3ccc(Cl)cc3SCc3cccnc32)CC1
Product: N#CN=C(NCc1ccc2c(c1)OCO2)N1CCC(C2c3ccc(Cl)cc3SCc3cccnc32)CC1

Procedure:
This compound could be prepared similarly from methyl 4-(8-chloro-5,11-dihydro-[1]benzothiepino[4,3-b]pyridin-11-yl)-N-cyano-1 -piperidine-carboximidothioate and 1,3-benzodioxol-5-ylmethylamine.
Reaction SMILES: F[C:2]1[CH:9]=[CH:8][C:7]([CH:10]=[O:11])=[CH:6][C:3]=1[C:4]#[N:5].[Cl:12][C:13]1[CH:14]=[C:15]([OH:19])[CH:16]=[N:17][CH:18]=1>>[Cl:12][C:13]1[CH:14]=[C:15]([O:19][C:2]2[CH:9]=[CH:8][C:7]([CH:10]=[O:11])=[CH:6][C:3]=2[C:4]#[N:5])[CH:16]=[N:17][CH:18]=1
Reactant: N#Cc1cc(C=O)ccc1F
Reactant: Oc1cncc(Cl)c1
Product: N#Cc1cc(C=O)ccc1Oc1cncc(Cl)c1

Procedure:
The title compound was prepared by a procedure similar to that described for D4 starting from 2-fluoro-5-formylbenzonitrile and 5-chloropyridin-3-ol.
Reaction SMILES: C[Al](C)C.[C:5]([C:7]([C:10]1[CH:19]=[CH:18][C:13]([C:14]([O:16]C)=O)=[CH:12][CH:11]=1)([CH3:9])[CH3:8])#[N:6].[CH3:20][CH:21]([CH3:44])[CH:22]([NH:27][C:28]([C:30]1[S:31][C:32]([C:35]2[CH:40]=[CH:39][C:38]([N+:41]([O-])=O)=[CH:37][CH:36]=2)=[CH:33][N:34]=1)=[O:29])[C:23]([O:25][CH3:26])=[O:24].[Cl-].[NH4+]>C1(C)C=CC=CC=1.C(Cl)Cl.O>[C:5]([C:7]([C:10]1[CH:11]=[CH:12][C:13]([C:14]([NH:41][C:38]2[CH:39]=[CH:40][C:35]([C:32]3[S:31][C:30]([C:28]([NH:27][CH:22]([CH:21]([CH3:44])[CH3:20])[C:23]([O:25][CH3:26])=[O:24])=[O:29])=[N:34][CH:33]=3)=[CH:36][CH:37]=2)=[O:16])=[CH:18][CH:19]=1)([CH3:8])[CH3:9])#[N:6]
Reactant: COC(=O)c1ccc(C(C)(C)C#N)cc1
Reactant: COC(=O)C(NC(=O)c1ncc(-c2ccc([N+](=O)[O-])cc2)s1)C(C)C
Agent: C[Al](C)C
Agent: [Cl-]
Agent: [NH4+]
Solvent: Cc1ccccc1
Solvent: ClCCl
Solvent: O
Product: COC(=O)C(NC(=O)c1ncc(-c2ccc(NC(=O)c3ccc(C(C)(C)C#N)cc3)cc2)s1)C(C)C
Temperature: 80 °C

Procedure:
Trimethyl aluminium (0.36 ml, 2M solution in toluene) was added to a solution of methyl 4-(2-cyanopropan-2-yl)benzoate (Intermediate 5, 100 mg) and methyl 2-(5-(4-aminophenyl) thiazole-2-carboxamido)-3-methylbutanoate (Intermediate 2, 150 mg) in toluene (12 ml). The reaction mixture was heated to 80° C. for 4 hours in a sealed tube. Reaction mass was cooled to RT, water was added and neutralized with saturated aqueous solution of ammonium chloride. Methylene chloride was added to it. Organic and aqueous layers were separated. Organic layer was washed successively with 1N HCl, saturated NaHCO3 and brine solution. It was then dried over sodium sulfate and concentrated to obtain dark brown residue which was purified by silica gel column chromatography in EtOAc-Petroleum ether to obtain pale brown solid. The solid was crystallized in CHCl3-petroleum ether to obtain title compound as off white solid. Yield: 75 mg (33%); 1HNMR (DMSO-d6, 300 MHz): δ 10.49 (s, 1H), 8.75 (d, 1H), 8.41 (s, 1H), 8.04 (d, 2H), 7.93 (d, 2H), 7.81 (d, 2H), 7.71 (d, 2H), 4.33 (m, 1H), 3.68 (s, 3H), 2.27 (m, 1H), 1.74 (s, 6H), 0.95 (m, 6H); MS (ES+) m/z 505.2 (M+1).
Reaction SMILES: [CH2:1]([O:8][CH2:9][CH:10]=[O:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH:12][CH2:13][C:14]1([CH2:17]O)[CH2:16][CH2:15]1>O.C1(C)C=CC(S(O)(=O)=O)=CC=1.C1(C)C=CC=CC=1>[CH2:1]([O:8][CH2:9][CH:10]1[O:12][CH2:13][C:14]2([CH2:16][CH2:15]2)[CH2:17][O:11]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: OCC1(CO)CC1
Reactant: O=CCOCc1ccccc1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: O
Solvent: Cc1ccccc1
Product: c1ccc(COCC2OCC3(CC3)CO2)cc1
Temperature: 25 °C
Yield: 78.2 %

Procedure:
A mixture of benzyloxyacetaldehyde (5 g, 33.3 mmol), 1,1-bis(hydroxymethyl)cyclopropane (4.08 g, 40 mmol), p-toluenesulfonic acid monohydrate (287 mg, 1.51 mmol) and toluene (70 ml) was refluxed for 2 hours while removing water by the Dean-Stark apparatus. After the reaction mixture was cooled to room temperature, triethylamine (4 ml) was added to the reaction mixture and the solvent was distilled off. The residue was purified by silica gel column chromatography (silica gel: 200 g, elution solvent: ethyl acetate/heptane=5/95 to 1/9) to obtain the title compound (6.1 g, yield: 78.2%) as a light yellow oil.
Reaction SMILES: [CH2:1]([NH:3][C:4]([C:6]1[CH:7]=[C:8]([CH:13]=[CH:14][N:15]=1)[C:9]([O:11]C)=[O:10])=[O:5])[CH3:2].[OH-].[Na+].Cl>CO>[CH2:1]([NH:3][C:4]([C:6]1[CH:7]=[C:8]([CH:13]=[CH:14][N:15]=1)[C:9]([OH:11])=[O:10])=[O:5])[CH3:2]
Reactant: CCNC(=O)c1cc(C(=O)OC)ccn1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: CCNC(=O)c1cc(C(=O)O)ccn1
Temperature: 25 °C
Reaction time: 3 h
Yield: 101.1 %

Procedure:
A mixture of methyl 2-(ethylcarbamoyl)isonicotinate (520 mg, 2.50 mmol, Step-1), 2M aqueous sodium hydroxide solution (2.5 mL), and methanol (6 mL) is stirred at room temperature for 3 hours. After addition of 2M hydrochloric acid (2.5 mL), the solvent is removed by evaporation. The residue is suspended in THF (20 mL), and the mixture is filtered through a pad of Celite. The filtrate is concentrated in vacuo to give 491 mg (quantitative yield) of the title compound as a white solid.
Reaction SMILES: Cl.[F:2][C:3]([F:18])([F:17])[O:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH2:12][CH2:13][NH:14][CH2:15][CH:16]=2)=[CH:7][CH:6]=1.Br[CH2:20][CH2:21][O:22][CH:23]1[CH2:28][CH2:27][CH2:26][CH2:25][O:24]1>>[O:24]1[CH2:25][CH2:26][CH2:27][CH2:28][CH:23]1[O:22][CH2:21][CH2:20][N:14]1[CH2:13][CH:12]=[C:11]([C:8]2[CH:9]=[CH:10][C:5]([O:4][C:3]([F:2])([F:17])[F:18])=[CH:6][CH:7]=2)[CH2:16][CH2:15]1
Reactant: BrCCOC1CCCCO1
Reactant: FC(F)(F)Oc1ccc(C2=CCNCC2)cc1
Agent: Cl
Product: FC(F)(F)Oc1ccc(C2=CCN(CCOC3CCCCO3)CC2)cc1
Yield: 47.1 %

Procedure:
Using 4-(4-trifluoromethoxyphenyl)-1,2,3,6-tetrahydropyridine monohydrochloride (680 mg, 2.43 mmol) and 2-(2-bromoethoxy)tetrahydropyran (610 mg, 2.92 mmol), 1-[2-(tetrahydropyran-2-yloxy)ethyl]-4-(4-trifluoromethoxyphenyl)-1,2,3,6-tetrahydropyridine (425 mg, yield 47%) as a pale brown oil was prepared in the same manner as described in Reference Example 15.
Reaction SMILES: [CH3:1][C:2]1([C:16]#[C:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH2:7][CH2:6][C:5]2[C:8]([CH3:15])=[C:9]([OH:14])[C:10]([CH3:13])=[C:11]([CH3:12])[C:4]=2[O:3]1.[C:24](OC(=O)C)(=[O:26])[CH3:25]>N1C=CC=CC=1>[C:24]([O:14][C:9]1[C:10]([CH3:13])=[C:11]([CH3:12])[C:4]2[O:3][C:2]([CH3:1])([C:16]#[C:17][C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=3)[CH2:7][CH2:6][C:5]=2[C:8]=1[CH3:15])(=[O:26])[CH3:25]
Reactant: Cc1c(C)c2c(c(C)c1O)CCC(C)(C#Cc1ccccc1)O2
Reactant: CC(=O)OC(C)=O
Solvent: c1ccncc1
Product: CC(=O)Oc1c(C)c(C)c2c(c1C)CCC(C)(C#Cc1ccccc1)O2

Procedure:
A mixture of 0.3 g of rac-3,4-dihydro-2,5,7,8-tetramethyl-2-(phenylethynyl)-2H-1-benzopyran-6-ol, 7 ml of pyridine and 0.5 ml of acetic anhydride was allowed to sit at room temperature over night. The reagents were evaporated under reduced pressure, at the end azeotropically with toluene. The residue was crystallized from hexane to give 0.21 g of colorless crystals with m.p. 123°-125°.
Reaction SMILES: Br[C:2]1[CH:8]=[CH:7][C:5]([OH:6])=[CH:4][C:3]=1[OH:9].[C:10]1(B(O)O)[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:2]1([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[C:3]([OH:9])=[CH:4][C:5]([OH:6])=[CH:7][CH:8]=1
Reactant: OB(O)c1ccccc1
Reactant: Oc1ccc(Br)c(O)c1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: COCCOC
Product: Oc1ccc(-c2ccccc2)c(O)c1
Temperature: 25 °C
Yield: 61 %

Procedure:
The synthesis was performed with reference to the known literature (Journal of Medicinal Chemistry, Vol. 44, p. 664, 2001). A solution of 4-bromoresorcinol (0.42 g, 2.2 mmol) in 1,2-dimethoxyethane (10 mL) was successively added with phenylboronic acid (0.37 g, 3.0 mmol), and 2 M aqueous sodium carbonate (3.5 mL), and the mixture was stirred at room temperature. After the inside of the reaction vessel was replaced with argon, the reaction mixture was added with tetrakis(triphenylphosphine)palladium(0) (0.14 g, 0.12 mmol), and the mixture was stirred at 95° C. for 6 hours in a sealed tube. The reaction mixture was added with ice water, the mixture was extracted with ethyl acetate, and then the organic layer was washed successively with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and then the residue was subjected to silica gel column chromatography (eluted with hexane/ethyl acetate (75:25)) to obtain biphenyl-2,4-diol (0.25 g, 61%).
Reaction SMILES: [CH3:1][C:2]1([C:7]2[S:11][C:10]([CH2:12][OH:13])=[CH:9][CH:8]=2)OCC[O:3]1.Cl.C(=O)([O-])O.[Na+]>C1COCC1>[OH:13][CH2:12][C:10]1[S:11][C:7]([C:2](=[O:3])[CH3:1])=[CH:8][CH:9]=1
Reactant: CC1(c2ccc(CO)s2)OCCO1
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: C1CCOC1
Product: CC(=O)c1ccc(CO)s1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a solution of [5-(2-methyl-1,3-dioxolan-2-yl)thien-2-yl]methanol prepared in the above step in THF (240 ml) was added 1N hydrochloric acid (48 ml) and the mixture was stirred for 2 hours at room temperature. Thereto was added sodium hydrogencarbonate (4.04 g) and the mixture was extracted with ethyl acetate. The organic layer was washed with a saturated aqueous sodium chloride solution and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure to give 1-[5-(hydroxymethyl)thien-2-yl]ethanone. This product was used in the next step without purification.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[N:13]=[C:12]([CH3:14])[CH:11]=[CH:10][CH:9]=1.[Se](=O)=[O:16]>O1CCOCC1>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[N:13]=[C:12]([CH:14]=[O:16])[CH:11]=[CH:10][CH:9]=1
Reactant: O=[Se]=O
Reactant: Cc1cccc(-c2ccccc2F)n1
Solvent: C1COCCO1
Product: O=Cc1cccc(-c2ccccc2F)n1
Reaction time: 144 h

Procedure:
2.0 g of 6-(2-fluorophenyl)-2-methylpyridine was dissolved in 250 ml of 1,4-dioxane. Selenium dioxide (2.67 g, Aldrich Gold Label) was added and the mixture was reluxed for 6 days. The solids were removed by filtration and the dioxane was evaporated. The crude 6-(2-fluorophenyl)-2-pyridinecarboxaldehyde was purified by chromatography on silica gel to afford pure 6-(2-fluorophenyl)-2-pyridinecarboxaldehyde.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:9])[C:4]([CH3:8])([CH3:7])[CH2:5][OH:6].ClC([O-])=O.[NH+]1C=CC=CC=1>C(Cl)Cl>[CH3:1][O:2][C:3](=[O:9])[C:4]([CH3:8])([CH3:7])[CH:5]=[O:6]
Reactant: COC(=O)C(C)(C)CO
Agent: O=C([O-])Cl
Agent: c1cc[nH+]cc1
Solvent: ClCCl
Product: COC(=O)C(C)(C)C=O
Temperature: 25 °C
Reaction time: 8 h
Yield: 56.7 %

Procedure:
To a solution of 2,2-dimethyl-3-oxo-propionic acid methyl ester (WHSS0374-001) (0.90 g; 5.44 mmol) in 1,2-dichloroethane (20 mL) was added 2-[4-(2,6-dichloro-benzyloxy)-phenyl]-morpholine (0.91 g, 2.7 mmol) and NaBH(OAc)3 (1.62 g; 7.62 mmol). The resulting mixture was stirred overnight at RT, and subsequently treated with 5% aqueous NaHCO3 (10 mL) and extracted with CH2Cl2 (3×30 ml). The combined organic layers were dried (Na2SO4), filtered and concentrated in vacuo. The residue was purified by column chromatography (SiO2, Et2O/hexanes 1:1) to afford 3-{2-[4-(2,6-dichloro-benzyloxy)-phenyl]-morpholin-4-yl}-2,2-dimethyl-propionic acid methyl ester (1.12 g) as a clear colourless oil. The required 2,2-dimethyl-3-oxo-propionic acid methyl ester was prepared as follows: To a solution of 2,2-dimethyl-3-hydroxypropionic acid methyl ester (10.00 g; 75.7 mmol) in CH2Cl2 (200 mL) was added pyridinium chloroformate (28.54 g; 132.4 mmol) in small portions, at 0° C. The reaction mixture was allowed to slowly warm to RT and stirred overnight. Subsequently, the mixture was diluted with CH2Cl2, filtered over kieselguhr, and concentrated in vacuo. The remaining oil was purified by column chromatography (SiO2, hexanes/Et2O 7:3) to afford 2,2-dimethyl-3-oxo-propionic acid methyl ester (5.59 g)
Reaction SMILES: [CH3:1][C:2]1([CH3:20])[O:7][C@H:6]([C@@H:8]([CH:18]=[CH2:19])[C@@H:9]([OH:17])[C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:5][CH2:4][O:3]1.[H-].[Na+].[CH3:23]I>C1COCC1>[CH3:1][C:2]1([CH3:20])[O:7][C@H:6]([C@@H:8]([CH:18]=[CH2:19])[C@@H:9]([O:17][CH3:23])[C:10]([O:12][C:13]([CH3:14])([CH3:16])[CH3:15])=[O:11])[CH2:5][CH2:4][O:3]1
Reactant: C=C[C@H]([C@@H]1CCOC(C)(C)O1)[C@@H](O)C(=O)OC(C)(C)C
Reactant: CI
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: C=C[C@H]([C@@H]1CCOC(C)(C)O1)[C@@H](OC)C(=O)OC(C)(C)C
Temperature: 23 °C
Reaction time: 2 h
Yield: 99.9 %

Procedure:
To a cold (0° C.) solution of (2R,3S)-t-Butyl 3-((S)-2,2-dimethyl-1,3-dioxan-4-yl)-2-hydroxypent-4-enoate (0.12 g, 0.40 mmol) in THF (5 mL) was added sodium hydride (20.0 mg, 0.8 mmol) followed by methyl iodide (50.0 μL, 0.80 mmol). The reaction was allowed to stir for 2 h at 23° C. then quenched with saturated ammonium chloride (5 mL). The reaction mixture was extracted with ethyl acetate (3×10 mL). The organic layers were combined, washed with brine and dried over anhydrous sodium sulfate. The solvent was reduced under vacuum and the residue was purified on silica gel to obtain 7 (0.12 g, 96% yield) as a colorless oil. Rf=0.54 (20% ethyl acetate/hexanes. 1H NMR (300 MHz, Chloroform-d) δ 5.74 (dt, J=17.2 Hz, 10.1 Hz, 1H), 5.22-4.93 (m, 2H), 4.29 (d, J=11.9 Hz, 1H), 3.95 (td, J=12.0 Hz, 2.8 Hz, 1H), 3.83-3.73 (m, 2H), 3.35 (s, 3H), 2.26 (td, J=9.9 Hz, 2.2 Hz, 1H), 1.79-1.71 (m, 1H), 1.43 (s, 9H), 1.41 (s, 3H), 1.35 (s, 3H), 1.19-1.07 (m, 1H). 13C NMR (75 MHz, CDCl3) δ 171.3, 132.9, 119.8, 98.2, 81.5, 80.5, 65.9, 60.0, 58.1, 52.3, 29.8, 28.4, 28.1, 19.1.
Reaction SMILES: [OH:1][CH:2]1[CH2:7][CH2:6][CH:5]([C:8]([O:10][CH3:11])=[O:9])[CH2:4][CH2:3]1.[Si:12](Cl)([C:15]([CH3:18])([CH3:17])[CH3:16])([CH3:14])[CH3:13].N1C=CN=C1>CN(C)C=O>[Si:12]([O:1][CH:2]1[CH2:3][CH2:4][CH:5]([C:8]([O:10][CH3:11])=[O:9])[CH2:6][CH2:7]1)([C:15]([CH3:18])([CH3:17])[CH3:16])([CH3:14])[CH3:13]
Reactant: CC(C)(C)[Si](C)(C)Cl
Reactant: COC(=O)C1CCC(O)CC1
Agent: c1c[nH]cn1
Solvent: CN(C)C=O
Product: COC(=O)C1CCC(O[Si](C)(C)C(C)(C)C)CC1
Temperature: 25 °C
Reaction time: 14 h

Procedure:
5.0 g (32 mmol) of methyl 4-hydroxycyclohexanecarboxylate were initially charged in 100 ml of dimethylformamide. 6.7 g (44 mmol) of tert-butyldimethylsilyl chloride and 4.1 g (60 mmol) of imidazole were then added, and the mixture was stirred at RT for another 14 h. The solvent was removed under reduced pressure and the residue was taken up in 100 ml of methyl tert-butyl ether and 100 ml of saturated aqueous sodium bicarbonate solution. The phases were separated, the organic phase was dried over magnesium sulphate and filtered and the solvent was removed under reduced pressure. Yield: 8.1 g (93% of theory)
Reaction SMILES: [CH3:1][C:2]1([CH3:20])[C:10]2[C:5](=[CH:6][CH:7]=[C:8](OS(C(F)(F)F)(=O)=O)[CH:9]=2)[C:4](=[O:19])[CH2:3]1.[CH3:21][O:22][C:23]1[CH:24]=[C:25](B(O)O)[CH:26]=[CH:27][CH:28]=1>>[CH3:21][O:22][C:23]1[CH:28]=[C:27]([C:8]2[CH:9]=[C:10]3[C:5](=[CH:6][CH:7]=2)[C:4](=[O:19])[CH2:3][C:2]3([CH3:20])[CH3:1])[CH:26]=[CH:25][CH:24]=1
Reactant: COc1cccc(B(O)O)c1
Reactant: CC1(C)CC(=O)c2ccc(OS(=O)(=O)C(F)(F)F)cc21
Product: COc1cccc(-c2ccc3c(c2)C(C)(C)CC3=O)c1

Procedure:
The title compound was prepared from trifluoro-methanesulfonic acid 3,3-dimethyl-1-oxo-indan-5-yl ester and 3-methoxyphenyl boronic acid according to the procedure described in example 21. MS (ES) m/z 267.2; HRMS: calcd for C18H18O2+H+, 267.13796; found (ESI, [M+H]+), 267.1386.
Reaction SMILES: [NH:1]1[C:5]2=[N:6][CH:7]=[CH:8][CH:9]=[C:4]2[CH:3]=[CH:2]1.ClC1C=CC=C(C(OO)=[O:18])C=1.O>COCCOC>[NH:1]1[C:5]2=[N+:6]([O-:18])[CH:7]=[CH:8][CH:9]=[C:4]2[CH:3]=[CH:2]1
Reactant: c1cnc2[nH]ccc2c1
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: O
Solvent: COCCOC
Product: [O-][n+]1cccc2cc[nH]c21
Reaction time: 1 h
Yield: 41 %

Procedure:
The commercially available 1H-pyrrolo[2,3-b]pyridine x7 (6.0 g, 50.8 mmol) is dissolved in 1,2-dimethoxyethane (50 ml). A solution of 70-75% m-chloroperbenzoic acid (17 g, 1.4 eq, 71.1 mmol) in 1,2-dimethoxyethane (40 ml) is added under cooling with cold water at a temperature below 25° C. The obtained suspension of the salt is stirred additionally for 1 h, kept overnight at −20° C. and filtered. The solid on the filter is washed with ether (2×30 ml) and air-dried. The obtained product is dissolved in a minimum of water. The pH of the solution is adjusted to 9 by the addition of aqueous K2CO3 under stirring and cooling with cold water. The formed suspension of the free N-oxide x257 is kept at +3° C. overnight and filtered. The product is washed with ice-cold water (2×10 ml) and dried over P2O5 under 1 mmHg to yield 1H-pyrrolo[2,3-b]pyridine 7-oxide x257 (3.4 g).
Reaction SMILES: [Cl:1]N1C(=O)CCC1=O.[C:9]([O:13][C:14](=[O:26])[NH:15][C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([CH2:22][CH2:23][CH:24]=[O:25])[CH:17]=1)([CH3:12])([CH3:11])[CH3:10].N1CCC[C@@H]1C(O)=O>C(Cl)Cl>[C:9]([O:13][C:14](=[O:26])[NH:15][C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([CH2:22][CH:23]([Cl:1])[CH:24]=[O:25])[CH:17]=1)([CH3:12])([CH3:10])[CH3:11]
Reactant: CC(C)(C)OC(=O)Nc1cccc(CCC=O)c1
Reactant: O=C1CCC(=O)N1Cl
Agent: O=C(O)[C@H]1CCCN1
Solvent: ClCCl
Product: CC(C)(C)OC(=O)Nc1cccc(CC(Cl)C=O)c1
Temperature: 25 °C
Reaction time: 2 h
Yield: 88.1 %

Procedure:
N-Chlorosuccinimide (0.27 g, 0.0020 mol) was added to a mixture of tert-butyl[3-(3-oxopropyl)phenyl]carbamate (0.50 g, 0.0020 mol) and D-proline (0.05 g, 0.0004 mol) in methylene chloride (5 mL) at 0° C. The reaction mixture was stirred at RT for 2 h and concentrated. The residue was purified by chromatography on silica gel with 30% EtOAc in hexanes to afford the desired product (0.50 g, 88%). LCMS: (M+H)=209.9/211.9.
Reaction SMILES: [CH:1]1([CH2:7][CH2:8][C@@H:9]([CH3:14])[CH2:10][CH2:11][CH:12]=[O:13])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.O.[Mn]([O-])(=O)(=O)=[O:17].[K+].S(=O)(O)[O-].[Na+]>C(O)(=O)C.CC(C)=O>[CH:1]1([CH2:7][CH2:8][C@@H:9]([CH3:14])[CH2:10][CH2:11][C:12]([OH:17])=[O:13])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: O=[Mn](=O)(=O)[O-]
Reactant: C[C@@H](CCC=O)CCC1CCCCC1
Agent: O=S([O-])O
Agent: [K+]
Agent: [Na+]
Solvent: CC(=O)O
Solvent: CC(C)=O
Solvent: O
Product: C[C@@H](CCC(=O)O)CCC1CCCCC1
Reaction time: 8 h
Yield: 54.1 %

Procedure:
A flask was charged with 7.12 g (36.3 mmol) of (R)-6-cyclohexyl-4-methyl-hexanal, 40 mL of water, 20 mL of acetone, 4 mL acetic acid, and 6.18 g (39.9 mmol) of potassium permanganate. The mixture was stirred vigorously overnight. The mixture was then treated with sat. aqueous sodium bisulfite until the liquid became clear. The liquid was extracted with hexanes. The combined hexane layers were washed with sat. aqueous sodium bisulfite until the hexane layer was clear. The hexane phases were dried with magnesium sulfate. The drying agent was filtered off and the solvent was removed under reduced pressure, which yielded 4.17 g (54% yield) of a clear oil: 1H NMR (400 MHz, CDCl3) ppm 0.89 (m, 5H), 1.13 (m, 3H) 1.25 (m, 5H) 1.66 (m, 8H) 2.40 (m, 2H). MS (APCI) m+1/z=211.