Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH:1][CH2:2][C:3]1[CH:12]=[C:11]2[C:6]([CH2:7][CH2:8][C:9](=[O:13])[NH:10]2)=[CH:5][CH:4]=1.Cl[CH2:15][CH2:16][CH2:17][O:18][CH3:19]>>[OH:1][CH2:2][C:3]1[CH:12]=[C:11]2[C:6]([CH2:7][CH2:8][C:9](=[O:13])[N:10]2[CH2:15][CH2:16][CH2:17][O:18][CH3:19])=[CH:5][CH:4]=1
Reactant: COCCCCl
Reactant: O=C1CCc2ccc(CO)cc2N1
Product: COCCCN1C(=O)CCc2ccc(CO)cc21

Procedure:
Analogously to Example 2c, 1.28 g of 7-hydroxymethyl-3,4-dihydro-1H-quinolin-2-one are reacted with 1.59 ml of 1-chloro-3-methoxypropane. The title compound is obtained as a slightly yellowish oil. Rf=0.24 (dichloromethane-methanol=95:5); Rt=2.71.
Reaction SMILES: [Cl:1][C:2]1[C:3]([F:31])=[C:4]([CH:8]2[CH2:12][N:11]([C:13](Cl)=[O:14])[CH:10]([CH2:16][C:17]([CH3:20])([CH3:19])[CH3:18])[C:9]2([C:23]2[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][C:24]=2[F:30])[C:21]#[N:22])[CH:5]=[CH:6][CH:7]=1.CC1(C)[O:37][C@@H:36]([CH2:38][CH2:39][NH2:40])[CH2:35][O:34]1.C(N(CC)CC)C.Cl>O1CCCC1>[OH:37][C@H:36]([CH2:35][OH:34])[CH2:38][CH2:39][NH:40][C:13]([N:11]1[CH2:12][CH:8]([C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[C:3]=2[F:31])[C:9]([C:23]2[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][C:24]=2[F:30])([C:21]#[N:22])[CH:10]1[CH2:16][C:17]([CH3:20])([CH3:18])[CH3:19])=[O:14]
Reactant: CC1(C)OC[C@H](CCN)O1
Reactant: CC(C)(C)CC1N(C(=O)Cl)CC(c2cccc(Cl)c2F)C1(C#N)c1ccc(Cl)cc1F
Agent: Cl
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: CC(C)(C)CC1N(C(=O)NCC[C@H](O)CO)CC(c2cccc(Cl)c2F)C1(C#N)c1ccc(Cl)cc1F
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 28.3 %

Procedure:
To a solution of rac-(2S,3R,4S)-4-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-3-cyano-2-(2,2-dimethyl-propyl)-pyrrolidine-1-carbonyl chloride (0.34 g, 0.7 mmol) in tetrahydrofuran (5 mL) was added 2-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl)-ethylamine (0.1 g, 0.71 mmol) and triethylamine (0.15 mL, 1 mmol). The reaction mixture was stirred at room temperature for 30 min. An aqueous HCl solution (1 N, 5 mL, 5 mmol) was added. The reaction mixture was stirred at room temperature for 1 h. The solvents were removed and the residue was partitioned between ethyl acetate and NaHCO3 (sat.) solution. The organic layer was separated, washed with water, brine, dried over MgSO4, and concentrated. The residue was purified by column chromatography (EtOAc) to afford rac-(2S,3R,4S)-4-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-3-cyano-2-(2,2-dimethyl-propyl)-pyrrolidine-1-carboxylic acid ((S)-3,4-dihydroxy-butyl)-amide as a white solid (0.11 g, 28%). HRMS (ES+) m/z Calcd for C27H31Cl2F2N3O3+H [(M+H)+]: 554.1784; Found: 554.1785.
Reaction SMILES: [CH2:1]([NH:3][C:4](=O)[CH2:5][O:6][C:7]1[C:12]([Cl:13])=[CH:11][C:10]([Cl:14])=[CH:9][C:8]=1[Cl:15])[CH3:2].C1(C)C=CC=CC=1.CSC.B>CO>[Cl:13][C:12]1[CH:11]=[C:10]([Cl:14])[CH:9]=[C:8]([Cl:15])[C:7]=1[O:6][CH2:5][CH2:4][NH:3][CH2:1][CH3:2]
Reactant: CCNC(=O)COc1c(Cl)cc(Cl)cc1Cl
Agent: B
Solvent: CSC
Solvent: CO
Solvent: Cc1ccccc1
Product: CCNCCOc1c(Cl)cc(Cl)cc1Cl
Temperature: 60 °C

Procedure:
N-ethyl-2,4,6-trichlorophenoxyacetamide, the product of Example 13, 10.5 gm, was added to 80 ml of toluene. 7.0 ml of borane methyl sulfide [BH3 (CH3)2S](2 equivalents) was then slowly added to the system. The system was heated at approximately 60° C for 18 hours at which time reaction completion was checked by IR spectroscopy. 50 ml of methanol was then slowly added to the system. After addition of the methanol, the system was acidified by bubbling in HCl gas. Afterwards, the system was refluxed for 1 hour. The solvent was removed by stripping. The resulting oil was dissolved in methanol which was then stripped. The oil was next dissolved in methylene chloride and the methylene chloride solution was washed with a sodium hydroxide solution and then with water. The methylene chloride was removed by stripping to give 10.0 gm of the N-ethyl ethanolamine 2,4,6-trichlorophenylether.
Reaction SMILES: [CH3:1][O:2][CH:3]([O:14][CH3:15])[C:4]1[CH:9]=[C:8](Cl)[CH:7]=[CH:6][C:5]=1[N+:11]([O-:13])=[O:12].[OH:16][CH:17]1[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]1.O>CN(C)C=O>[CH3:1][O:2][CH:3]([O:14][CH3:15])[C:4]1[CH:9]=[C:8]([N:20]2[CH2:21][CH2:22][CH:17]([OH:16])[CH2:18][CH2:19]2)[CH:7]=[CH:6][C:5]=1[N+:11]([O-:13])=[O:12]
Reactant: COC(OC)c1cc(Cl)ccc1[N+](=O)[O-]
Reactant: OC1CCNCC1
Solvent: O
Solvent: CN(C)C=O
Product: COC(OC)c1cc(N2CCC(O)CC2)ccc1[N+](=O)[O-]
Yield: 67.2 %

Procedure:
A solution of 5 g of 5-chloro-2-nitrobenzaldehyde dimethylacetal and 8.8 g of 4-hydroxypiperidine in 20 ml of N,N-dimethylformamide was heated at 80 ° C. for 14 hr. The reaction mixture was poured into water, and extracted with ethyl acetate. The extract was washed with water, dried, and evaporated under a reduced pressure. The residue was purified by a silica gel column chromatography to give 4.3 g of 5-(4-hydroxypiperidino)-2-nitrobenzaldehyde dimethylacetal.
Reaction SMILES: [Mg].[CH:2]1[CH2:6][CH:5]=[CH:4][CH:3]=1.F[C:8]1[CH:13]=[CH:12][C:11]([F:14])=[CH:10][C:9]=1Br>C1COCC1>[F:14][C:11]1[CH:10]=[C:9]2[C:8](=[CH:13][CH:12]=1)[CH:4]1[CH2:5][CH:6]2[CH:2]=[CH:3]1
Reactant: C1=CCC=C1
Reactant: Fc1ccc(F)c(Br)c1
Agent: [Mg]
Solvent: C1CCOC1
Product: Fc1ccc2c(c1)C1C=CC2C1
Reaction time: 0.25 h

Procedure:
Magnesium turnings (0.66 g, 27.2 mmol) were stirred in anhydrous THF (10 mL) in a flame dried 75 mL 3 neck round bottom flask equipped with a non-equalizing addition funnel with a N2 flow adapter, magnetic stirrer and efficient condenser equipped with a N2 flow adapter. The flask was stirred and warmed to reflux by a removable heating mantle. 2,5-Difluorobromobenzene (0.1 g) was added followed by of 3N EtMgBr in THF (0.1 mL). The addition funnel was charged with an intimate mixture of cyclopentadiene (1.71 g, 25.9 mmol) and 2,5-difluorobromobenzene (5.0 g, 25.9 mmol). Small portions (˜0.2 mL) of the intimate mixture were introduced to assist initiation (˜4 times). After ˜15 minutes, the reaction initiated (exotherm, and vapor condensation) and heating was maintained as necessary during the addition of the contents of the addition funnel. The reaction was then maintained at reflux for 1 hour.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])[CH:5]=[CH:6][CH:7]=1.F[C:17]1[CH:18]=[CH:19][C:20]([N+:24]([O-:26])=[O:25])=[C:21]([CH:23]=1)[NH2:22].C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O.C(OCC)(=O)C.CCCCCC>[NH2:22][C:21]1[CH:23]=[C:17]([CH:18]=[CH:19][C:20]=1[N+:24]([O-:26])=[O:25])[O:1][C:2]1[CH:3]=[C:4]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:12])([CH3:14])[CH3:13])[CH:5]=[CH:6][CH:7]=1
Reactant: CC(C)(C)OC(=O)Nc1cccc(O)c1
Reactant: Nc1cc(F)ccc1[N+](=O)[O-]
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCCCCC
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CC(C)(C)OC(=O)Nc1cccc(Oc2ccc([N+](=O)[O-])c(N)c2)c1
Temperature: 100 °C
Reaction time: 14 h
Yield: 68.4 %

Procedure:
To a solution of tert-butyl (3-hydroxyphenyl)carbamate (6.89 g, 32.9 mmol) and 5-fluoro-2-nitroaniline (5.09 g, 32.6 mmol) in N,N-dimethylformamide (100 mL) was added potassium carbonate (11.2 g, 80.9 mmol), and the mixture was vigorously stirred at 100° C. for 14 hr. The reaction mixture was cooled to room temperature, diluted with ethyl acetate (125 ml) and hexane (125 mL), washed with water (150 mL×2) and saturated brine (100 mL), successively, and dried over anhydrous magnesium sulfate. The insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography (ethyl acetate/hexane=2/98→30/70) to give the title compound (7.7 g, 69%) as a yellow solid.
Reaction SMILES: [CH3:1][NH:2][S:3](Cl)(=[O:5])=[O:4].[NH2:7][C:8]1[CH:27]=[CH:26][C:11]([O:12][CH2:13][CH:14]2[CH2:19][CH2:18][N:17]([C:20]3[CH:25]=[CH:24][N:23]=[CH:22][CH:21]=3)[CH2:16][CH2:15]2)=[CH:10][CH:9]=1>N1C=CC=CC=1>[CH3:1][NH:2][S:3]([NH:7][C:8]1[CH:27]=[CH:26][C:11]([O:12][CH2:13][CH:14]2[CH2:15][CH2:16][N:17]([C:20]3[CH:25]=[CH:24][N:23]=[CH:22][CH:21]=3)[CH2:18][CH2:19]2)=[CH:10][CH:9]=1)(=[O:5])=[O:4]
Reactant: CNS(=O)(=O)Cl
Reactant: Nc1ccc(OCC2CCN(c3ccncc3)CC2)cc1
Solvent: c1ccncc1
Product: CNS(=O)(=O)Nc1ccc(OCC2CCN(c3ccncc3)CC2)cc1
Temperature: 25 °C
Reaction time: 6 h
Yield: 39.6 %

Procedure:
Methylsulphamoyl chloride (0.39 g) was added dropwise to a stirred solution of 4-[(4-aminophenoxy)methyl]-1-[4-pyridyl]-piperidine (see Preparation 4) (0.57 g) in pyridine (15 ml) and the mixture was stirred at room temperature for 6 hours. An additional 0.39 g of methylsulphamoyl chloride was then added and the mixture was stirred for a further 18 hours and then evaporated. The residue was partitioned between sodium bicarbonate solution and ethyl acetate. The organic layer was separated and the aqueous layer was extracted several times with ethyl acetate. The combined organic layers were washed with water, dried (Na2SO4) and evaporated. The solid residue was crystallised from ethanol to give the title compound, (0.30 g), m.p. 170.5°-172.5°.
Reaction SMILES: [O:1]1[CH:5]=[CH:4][C:3]([C:6]2(O)[C:14]3[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=3)[CH2:8][CH2:7]2)=[CH:2]1.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[O:1]1[CH:5]=[CH:4][C:3]([CH:6]2[C:14]3[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=3)[CH:8]=[CH:7]2)=[CH:2]1
Reactant: OC1(c2ccoc2)CCc2ccccc21
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: Cc1ccccc1
Product: C1=CC(c2ccoc2)c2ccccc21
Yield: 61.7 %

Procedure:
To a mixture of 5 g (0.024 mol) of 1-(3-furyl)-indan-1-ol in 500 ml of toluene was added 50 mg of p-toluenesulfonic acid and the mixture was placed on a Rotovap® and the solvent was distilled in vacuo (40 mm) until a residue was obtained. The residue was chromatographed (silica, 1:1 hexane/methylene chloride) to afford 2.7 g (61.3%) of 1-(3-furyl)-indene as a clear oil.
Reaction SMILES: [N:1](CC1C=CC=CC=1)=[N+:2]=[N-:3].[C:11]([OH:17])(=[O:16])[CH2:12][CH2:13][C:14]#[CH:15]>>[NH:1]1[CH:15]=[C:14]([CH2:13][CH2:12][C:11]([OH:17])=[O:16])[N:3]=[N:2]1
Reactant: C#CCCC(=O)O
Reactant: [N-]=[N+]=NCc1ccccc1
Product: O=C(O)CCc1c[nH]nn1

Procedure:
The title compound was prepared from (azidomethyl)benzene and pent-4-ynoic acid analogously to Example 17, steps 3 and 4;
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]([NH:16][NH2:17])=[O:15])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:18]([O:20][CH2:21][C:22](O)=[O:23])[CH3:19].Cl.CN(C)CCCN=C=NCC.O.ON1C2C=CC=CC=2N=N1.C(N(CC)CC)C>CN(C)C=O>[CH2:18]([O:20][CH2:21][C:22]([NH:17][NH:16][C:14]([CH:11]1[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH2:9][CH2:10]1)=[O:15])=[O:23])[CH3:19]
Reactant: CC(C)(C)OC(=O)N1CCC(C(=O)NN)CC1
Reactant: CCOCC(=O)O
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Solvent: O
Product: CCOCC(=O)NNC(=O)C1CCN(C(=O)OC(C)(C)C)CC1
Temperature: 25 °C
Reaction time: 18 h

Procedure:
A mixture of 4-hydrazinocarbonyl-piperidine-1-carboxylic acid tert-butyl ester (WO 2000039125, prep 27) (3 g, 12.33 mmol), ethoxyacetic acid (1.28 mL, 13.56 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (2.6 g, 13.56 mmol), 1-hydroxybenzotriazole hydrate (1.83 g, 13.56 mmol) and triethylamine (2.1 mL, 14.8 mmol) in N,N-dimethylformamide (15 mL) was stirred at room temperature for 18 hours. The mixture was concentrated under reduced pressure and the residue was partitioned between ethyl acetate and aqueous sodium carbonate solution. The layers were separated, the organic phase was dried over MgSO4 and evaporated under reduced pressure to provide the title compound as an oil, that crystallised on standing.
Reaction SMILES: [N-:1]=[C:2]=[O:3].[CH:4]1[C:9]([CH2:10][C:11]2[CH:12]=[CH:13][C:14]([NH2:17])=[CH:15][CH:16]=2)=[CH:8][CH:7]=[C:6](N)[CH:5]=1.[NH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.[CH2:26]=[O:27]>>[CH:12]1[C:11]([CH2:10][C:9]2[CH:8]=[CH:7][C:6]([N:1]=[C:2]=[O:3])=[CH:5][CH:4]=2)=[CH:16][CH:15]=[C:14]([N:17]=[C:26]=[O:27])[CH:13]=1.[NH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.[CH2:2]=[O:3]
Reactant: Nc1ccc(Cc2ccc(N)cc2)cc1
Reactant: [N-]=C=O
Agent: C=O
Solvent: Nc1ccccc1
Product: O=C=Nc1ccc(Cc2ccc(N=C=O)cc2)cc1

Procedure:
The instant emulsions are preferably used as binders for materials containing lignocellulose, as already mentioned. Emulsions which have proved to be particularly suitable for this purpose are those in which the isocyanate component (see German Offenlegungsschrift No. 2,711,958) is the phosgenation product for the undistilled bottom fractions. These may be obtained, for example, by the removal of 25 to 90% by weight, preferably 30 to 85% by weight of 2,2'-, 2,4'- and/or 4,4'-diaminodiphenylmethane from an aniline/formaldehyde condensate. The undistilled bottom fraction may also be obtained by the removal of 25 to 90% by weight, preferably 30 to 85% by weight of 2,2'-, 2,4'- and/or 4,4'-diisocyanatodiphenylmethane from the crude phosgenation product of an aniline/formaldehyde condensate. In either case, the isocyanate component should contain 35 to 70% by weight, preferably 45 to 60% by weight of diisocyanatodiphenylmethane. The 2,4'-diisocyanatodiphenylmethane content is from 1 to 8% by weight, preferably from 2 to 5% by weight and the content of 2,2'-diisocyanatodiphenylmethane is from 0 to 2% by weight. In either case, the isocyanate component has a viscosity at 25° C. of 50 to 600 mPas, preferably 200 to 500 mPas, and an isocyanate content from 28 to 32% by weight.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6](=[O:11])[C:5]2([CH2:20][C:21](O)=[O:22])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[O:18][CH3:19].[S:24]1[CH:28]=[CH:27][N:26]=[C:25]1[N:29]1[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]1>>[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6](=[O:11])[C:5]2([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[O:18][CH3:19])[CH2:20][C:21](=[O:22])[N:32]1[CH2:33][CH2:34][N:29]([C:25]2[S:24][CH:28]=[CH:27][N:26]=2)[CH2:30][CH2:31]1
Reactant: COc1ccccc1C1(CC(=O)O)C(=O)Nc2ccc(Cl)cc21
Reactant: c1csc(N2CCNCC2)n1
Product: COc1ccccc1C1(CC(=O)N2CCN(c3nccs3)CC2)C(=O)Nc2ccc(Cl)cc21
Yield: 83.8 %

Procedure:
With 800 mg of [5-chloro-3-(2-methoxyphenyl)-2-oxo-2,3-dihydro-1H-indol-3-yl]acetic acid, which is the compound described in Preparation 1.1 of the brochure Publication No. WO03/008407, and 449 mg of 1-(1,3-thiazol-2-yl)piperazine as starting materials, reaction manipulation and post-treatment were carried out by a similar method to Step 45-1, and the obtained residue was crystallized from EtOAc and n-hexane to obtain 976 mg of the title compound (colorless crystal).
Reaction SMILES: Cl[C:2]1[C:6]2[CH:7]=[CH:8][C:9]([O:11][CH3:12])=[CH:10][C:5]=2[O:4][N:3]=1.[NH:13]1[CH2:19][CH2:18][CH2:17][NH:16][CH2:15][CH2:14]1>CCOC(C)=O>[N:13]1([C:2]2[C:6]3[CH:7]=[CH:8][C:9]([O:11][CH3:12])=[CH:10][C:5]=3[O:4][N:3]=2)[CH2:19][CH2:18][CH2:17][NH:16][CH2:15][CH2:14]1
Reactant: C1CNCCNC1
Reactant: COc1ccc2c(Cl)noc2c1
Solvent: CCOC(C)=O
Product: COc1ccc2c(N3CCCNCC3)noc2c1
Temperature: 140 °C
Reaction time: 0.75 h

Procedure:
3-Chloro-6-methoxy-1,2-benzisoxazole (5.0 g, 27.2 mml) and homopiperazine (8.2 g, 81.6 mmol) were combined and mechanically stirred under N2 at 140° C. for 45 minutes. The reaction mixture was cooled to room temperature, dissolved with EtOAc (500 ml), and the solution was washed with water, brine, dried over MgSO4, and concentrated in vacuo. Flash column chromatography (silica gel, 20% MeOH/CH2Cl2) provided the product (2.0 g, m.p. 74°-75° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:16]=[CH:15][C:6]([C:7]([O:9][CH2:10][C@H:11]([OH:14])[CH2:12][OH:13])=[O:8])=[CH:5][CH:4]=1.O([Si:25]([C:28]([CH3:31])([CH3:30])[CH3:29])([CH3:27])[CH3:26])S(C(F)(F)F)(=O)=O>C(Cl)Cl>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([C:7]([O:9][CH2:10][C@H:11]([O:14][Si:25]([C:28]([CH3:31])([CH3:30])[CH3:29])([CH3:27])[CH3:26])[CH2:12][O:13][Si:25]([C:28]([CH3:31])([CH3:30])[CH3:29])([CH3:27])[CH3:26])=[O:8])=[CH:15][CH:16]=1
Reactant: CC(C)(C)[Si](C)(C)OS(=O)(=O)C(F)(F)F
Reactant: COc1ccc(C(=O)OC[C@H](O)CO)cc1
Solvent: ClCCl
Product: COc1ccc(C(=O)OC[C@@H](CO[Si](C)(C)C(C)(C)C)O[Si](C)(C)C(C)(C)C)cc1
Temperature: 0 °C
Reaction time: 0.08 h

Procedure:
To a 1.0 L RB flask containing (R)-2,3-dihydroxypropyl 4-methoxybenzoate (4.800 g, 21.2 mmol; according to the procedure described in Corey, E. J.; Guzman-Perez, A.; and Noe, M. C. J. Am. Chem. Soc. 1995, 117, 10805-10816) was added DCM (100 mL) and the mixture was allowed to stir at 0° C. for 5 minutes. At this time, TEA (8.87 ml, 63.7 mmol) was added and the reaction was allowed to stir for 5 min before the dropwise addition of tert-butyldimethylsilyl triflate (10.2 ml, 44.6 mmol) via syringe. The reaction was allowed to stir for 1 h and then quenched by pouring into HCl (0.1 N, 100 mL). The aqueous layer was extracted with DCM (2×75 mL). The combined organics were washed with HCl (0.1 N, 2×150 mL), sodium bicarbonate (1×150 mL, sat), brine, dried sodium sulfate. The concentrated solution was passed through a plug of silica gel to and concentrated to give the title compound as a colorless oil.
Reaction SMILES: [O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]1[CH:19]=[CH:18][C:13]([C:14](OC)=[O:15])=[CH:12][CH:11]=1>C1COCC1>[O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]1[CH:19]=[CH:18][C:13]([CH2:14][OH:15])=[CH:12][CH:11]=1
Reactant: COC(=O)c1ccc(-c2nc3ccccc3o2)cc1
Solvent: C1CCOC1
Product: OCc1ccc(-c2nc3ccccc3o2)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 88.8 %

Procedure:
To a solution of methyl 4-(benzoxazol-2-yl)-benzoate (0.20 g, 0.8 mmol) in THF (8 mL) at −78° C. was added a solution of DEBAL-H (4.0 mL, 1.0 M in THF, 4.0 mmol). The reaction was allowed to warm to room temperature, stirred for 1 h and quenched with a saturated potassium sodium tartrate solution (15 mL). The biphasic mixture was stirred vigorously for 1 h, the phases separated and the organic layer dried (MgSO4), filtered and concentrated to give the title alcohol (0.16 g, 89%). 1H NMR (CDCl3) δ1.80 (t, 1H (OH)), 4.82 (d, 2H, J=6.0 Hz), 7.36 (m, 2H), 7.55 (d, 2H, J=8.4 Hz), 7.60 (m, 1H), 7.78 (m, 1H), 8.26 (d, 2H, J=8.4 Hz).
Reaction SMILES: Br[C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=[C:4]([O:11][CH3:12])[CH:3]=1.[CH:13]([C:15]1[CH:16]=[C:17]([NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])[CH:18]=[CH:19][CH:20]=1)=[CH2:14].C(N(CC)CC)C.C(OCC)(=O)C>CCCC[N+](CCCC)(CCCC)CCCC.[Cl-].CN(C)C=O.[Cl-].[Na+].O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:12][O:11][C:4]1[CH:3]=[C:2](/[CH:14]=[CH:13]/[C:15]2[CH:16]=[C:17]([NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])[CH:18]=[CH:19][CH:20]=2)[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=1
Reactant: C=Cc1cccc(NC(=O)OC(C)(C)C)c1
Reactant: COc1cc(Br)cc([N+](=O)[O-])c1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Solvent: CCN(CC)CC
Solvent: O
Solvent: CCOC(C)=O
Product: COc1cc(/C=C/c2cccc(NC(=O)OC(C)(C)C)c2)cc([N+](=O)[O-])c1
Temperature: 110 °C
Yield: 60.7 %

Procedure:
1-Bromo-3-methoxy-5-nitrobenzene (0.50 g, 2.00 mmol), tert-butyl (3-vinylphenyl)carbamate (0.56 g, 2.15 mmol), tetra-N-butylammonium chloride (59.9 mg, 0.22 mmol), palladium acetate (48 mg, 0.22 mmol), and triethylamine (0.75 mL, 5.39 mmol) were stirred in N,N-dimethylformamide (5.7 mL) and heated to 110° C. for 20 hours. The mixture was cooled to RT, ethyl acetate and brine were added. The ethyl acetate was separated and the aqueous layer was extracted two more times with ethyl acetate. The combined ethyl acetate extracts were dried over sodium sulfate, filtered, and concentrated. Purification by silica chromatography using ethyl acetate and hexanes gave the desired compound (0.45 g, 60%). LCMS for C20H23N2O5 (M+H)+: m/z=371.2.
Reaction SMILES: C([O:3][C:4](=[O:18])[CH:5]=[CH:6][CH:7]=[CH:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[CH:11][C:10]=1[Cl:17])C.C1COCC1.[OH-].[K+]>CO.O>[Cl:17][C:10]1[CH:11]=[C:12]([O:15][CH3:16])[CH:13]=[CH:14][C:9]=1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]([OH:18])=[O:3]
Reactant: CCOC(=O)C=CC=Cc1ccc(OC)cc1Cl
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Solvent: CO
Product: COc1ccc(C=CC=CC(=O)O)c(Cl)c1
Temperature: 25 °C
Reaction time: 1.5 h

Procedure:
The crude ester product was taken up in 200 mL each of methanol and THF and then cooled to 0° C. To this mixture was added a solution of KOH (19 g, 0.338 mol, 3 eq.) in 200 mL H2O. The mixture was stirred at room temperature for 1.5 hr and the organic solvent was evaporated. The aqueous layer was diluted with 300 mL H2O and washed with ether to remove the mineral oil. It was then cooled in an ice-bath and acidified with concentrated HCl to ˜pH 2. The thick precipitate was filtered and rinsed with water, then dried in a vacuum oven at 75° C. to provide 26.2 g of 5-(2-chloro-4-methoxy-phenyl)-penta-2,4-dienoic acid.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([C@H:10]2[CH2:14][CH2:13][CH2:12][C@@H:11]2[OH:15])[CH:5]=[C:6]([F:9])[C:7]=1[F:8].CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O>C(Cl)Cl>[F:1][C:2]1[CH:3]=[C:4]([CH:10]2[CH2:14][CH2:13][CH2:12][C:11]2=[O:15])[CH:5]=[C:6]([F:9])[C:7]=1[F:8]
Reactant: O[C@H]1CCC[C@@H]1c1cc(F)c(F)c(F)c1
Agent: CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21
Solvent: ClCCl
Product: O=C1CCCC1c1cc(F)c(F)c(F)c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 31.3 %

Procedure:
To a solution of (1S,2R)-2-(3,4,5-trifluorophenyl)cyclopentanol (1 g, 4.63 mmol) in CH2Cl2 (20 mL) was added Dess-Martin periodinane (2.354 g, 5.55 mmol). The reaction mixture was stirred at rt for 1 h. The reaction was diluted with dichloromethane and quenched with the addition of 1 N NaOH. The organic layer was collected, dried (Na2SO4) and concentrated. The crude product was purified by column chromatography on silica gel to afford 2-(3,4,5-trifluorophenyl)cyclopentanone (310 mg, 1.447 mmol, 31.3% yield). LC-MS (M+H)+=215.1.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[NH:9][C:10](=[O:18])[C:11]3[C:16]([CH:17]=2)=[CH:15][CH:14]=[N:13][CH:12]=3)=[CH:4][CH:3]=1.[CH3:19][N:20]1[CH:24]=[C:23](B2OC(C)(C)C(C)(C)O2)[CH:22]=[N:21]1.C(=O)([O-])O.[Na+]>CN(C=O)C.O.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl>[CH3:19][N:20]1[CH:24]=[C:23]([C:2]2[CH:7]=[CH:6][C:5]([C:8]3[NH:9][C:10](=[O:18])[C:11]4[C:16]([CH:17]=3)=[CH:15][CH:14]=[N:13][CH:12]=4)=[CH:4][CH:3]=2)[CH:22]=[N:21]1
Reactant: O=c1[nH]c(-c2ccc(Br)cc2)cc2ccncc12
Reactant: Cn1cc(B2OC(C)(C)C(C)(C)O2)cn1
Agent: Cl[Pd]Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: Cn1cc(-c2ccc(-c3cc4ccncc4c(=O)[nH]3)cc2)cn1
Temperature: 40 °C
Reaction time: 20 h

Procedure:
A suspension of 3-(4-bromo-phenyl)-2H-[2,7]naphthyridin-1-one (63.2 mg, 0.210 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (65.5 mg, 0.32 mmol) and sodium hydrogen carbonate (21.2 mg, 0.25 mmol) in DMF (1 ml) and water (0.25 ml) is flushed with nitrogen and heated to 40° C. Then bis(triphenylphosphine)-palladium(II)-chloride (3.0 mg, 0.004 mmol) is added. The reaction mixture is heated to 80° C. and stirred at this temperature for 20 hours. The mixture is allowed to cool to room temperature and excess water is added. The resulting precipitate is filtered off washed with water and dried under vacuum to afford 3-[4-(1-methyl-1H-pyrazol-4-yl)-phenyl]-2H-[2,7]naphthyridin-1-one as olive green solid; HPLC/MS 1.33 min (A), [M+H] 303;