Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][N:2]([CH3:26])[CH2:3][CH2:4][N:5]([CH3:25])[C:6]1[S:7][C:8]2[CH:14]=[C:13]([NH:15][C:16](=[O:24])[C:17]3[CH:22]=[CH:21][C:20](I)=[CH:19][CH:18]=3)[CH:12]=[CH:11][C:9]=2[N:10]=1.[CH3:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=1B(O)O>>[CH3:1][N:2]([CH3:26])[CH2:3][CH2:4][N:5]([CH3:25])[C:6]1[S:7][C:8]2[CH:14]=[C:13]([NH:15][C:16]([C:17]3[CH:22]=[CH:21][C:20]([C:29]4[CH:30]=[CH:31][CH:32]=[CH:33][C:28]=4[CH3:27])=[CH:19][CH:18]=3)=[O:24])[CH:12]=[CH:11][C:9]=2[N:10]=1
Reactant: Cc1ccccc1B(O)O
Reactant: CN(C)CCN(C)c1nc2ccc(NC(=O)c3ccc(I)cc3)cc2s1
Product: Cc1ccccc1-c1ccc(C(=O)Nc2ccc3nc(N(C)CCN(C)C)sc3c2)cc1

Procedure:
The title compound is prepared by following a procedure analogous to Example 113, Step 1, using N-{2-[(2-dimethylamino-ethyl)-methyl-amino]-benzothiazol-6-yl}-4-iodo-benzamide (0.15 g, 0.31 mmol) and 2-methylphenylboronic acid (0.051 g, 0.38 mmol) to afford 0.098 g (71%). LC/MS, Retention time=4.75 min; (m/z): calcd for C26H28N4OS (M+H)+: 445.6; found: 445.0.
Reaction SMILES: [NH2:1][CH2:2][CH2:3][C:4]1[N:5]([CH:28]([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[C:6]2[C:11]([C:12]=1[CH2:13][CH2:14][O:15][C:16]1[CH:25]=[CH:24][C:19]([C:20]([O:22]C)=[O:21])=[C:18]([F:26])[CH:17]=1)=[CH:10][C:9]([Cl:27])=[CH:8][CH:7]=2.[Cl:41][C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][C:43]=1[S:48](Cl)(=[O:50])=[O:49]>>[CH:28]([N:5]1[C:6]2[C:11](=[CH:10][C:9]([Cl:27])=[CH:8][CH:7]=2)[C:12]([CH2:13][CH2:14][O:15][C:16]2[CH:25]=[CH:24][C:19]([C:20]([OH:22])=[O:21])=[C:18]([F:26])[CH:17]=2)=[C:4]1[CH2:3][CH2:2][NH:1][S:48]([C:43]1[CH:44]=[CH:45][CH:46]=[CH:47][C:42]=1[Cl:41])(=[O:50])=[O:49])([C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)[C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1
Reactant: O=S(=O)(Cl)c1ccccc1Cl
Reactant: COC(=O)c1ccc(OCCc2c(CCN)n(C(c3ccccc3)c3ccccc3)c3ccc(Cl)cc23)cc1F
Product: O=C(O)c1ccc(OCCc2c(CCNS(=O)(=O)c3ccccc3Cl)n(C(c3ccccc3)c3ccccc3)c3ccc(Cl)cc23)cc1F
Yield: 73 %

Procedure:
The methyl 4-{2-[2-(2-amino-ethyl)-1-benzhydryl-5-chloro-1H-indol-3-yl]-ethoxy}-2-fluoro-benzoate from above and 2-chloro-benzenesulfonyl chloride were reacted according to the procedure in Example 1 Step 7 to generate the desired product in 73% yield.
Reaction SMILES: CS(C1C=CC(N2CCCC2)=C(C=1)C(O)=O)(=O)=O.Cl[C:20]1[CH:28]=[CH:27][C:26]([S:29](=[O:34])(=[O:33])[NH:30][CH2:31][CH3:32])=[CH:25][C:21]=1[C:22]([OH:24])=[O:23].[NH:35]1[CH2:40][CH2:39][O:38][CH2:37][CH2:36]1>>[CH2:31]([NH:30][S:29]([C:26]1[CH:27]=[CH:28][C:20]([N:35]2[CH2:40][CH2:39][O:38][CH2:37][CH2:36]2)=[C:21]([CH:25]=1)[C:22]([OH:24])=[O:23])(=[O:34])=[O:33])[CH3:32]
Reactant: C1COCCN1
Reactant: CCNS(=O)(=O)c1ccc(Cl)c(C(=O)O)c1
Agent: CS(=O)(=O)c1ccc(N2CCCC2)c(C(=O)O)c1
Product: CCNS(=O)(=O)c1ccc(N2CCOCC2)c(C(=O)O)c1
Yield: 42 %

Procedure:
The title compound was synthesised according to the procedure described for the synthesis of 5-Methanesulfonyl-2-pyrrolidin-1-yl-benzoic acid from 2-Chloro-5-ethylsulfamoyl-benzoic acid and morpholine and obtained in 42% yield. MS (m/e): 313.2 (MH−, 100%).
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][CH2:4][CH:3]([CH2:7][NH:8][C:9]([C:11]2[C:15]3[N:16]=[CH:17][N:18]=[C:19]([C:20]4[C:28]5[O:27][CH2:26][O:25][C:24]=5[CH:23]=[CH:22][C:21]=4[O:29][CH2:30][CH:31]4[CH2:33][CH2:32]4)[C:14]=3[NH:13][CH:12]=2)=[O:10])[CH2:2]1.[CH:34](OC(=O)C)=[O:35]>>[CH:34]([N:1]1[CH2:6][CH2:5][CH2:4][CH:3]([CH2:7][NH:8][C:9]([C:11]2[C:15]3[N:16]=[CH:17][N:18]=[C:19]([C:20]4[C:28]5[O:27][CH2:26][O:25][C:24]=5[CH:23]=[CH:22][C:21]=4[O:29][CH2:30][CH:31]4[CH2:33][CH2:32]4)[C:14]=3[NH:13][CH:12]=2)=[O:10])[CH2:2]1)=[O:35]
Reactant: CC(=O)OC=O
Reactant: O=C(NCC1CCCNC1)c1c[nH]c2c(-c3c(OCC4CC4)ccc4c3OCO4)ncnc12
Product: O=CN1CCCC(CNC(=O)c2c[nH]c3c(-c4c(OCC5CC5)ccc5c4OCO5)ncnc23)C1

Procedure:
Starting from 4-(5-cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxylic acid (piperidin-3-ylmethyl)-amide (example A145) and acetic formic anhydride the title compound is obtained as colorless solid.
Reaction SMILES: [CH3:1][O:2][C:3]1[C:8]([NH2:9])=[CH:7][C:6]([C:10]#[C:11][C:12]2[C:13]([CH3:24])=[N:14][CH:15]=[N:16][C:17]=2[N:18]2[CH2:23][CH2:22][O:21][CH2:20][CH2:19]2)=[CH:5][N:4]=1.[Cl:25][C:26]1[CH:31]=[CH:30][C:29]([S:32](Cl)(=[O:34])=[O:33])=[CH:28][CH:27]=1.N1C=CC=CC=1.O>C(Cl)Cl>[Cl:25][C:26]1[CH:31]=[CH:30][C:29]([S:32]([NH:9][C:8]2[C:3]([O:2][CH3:1])=[N:4][CH:5]=[C:6]([C:10]#[C:11][C:12]3[C:13]([CH3:24])=[N:14][CH:15]=[N:16][C:17]=3[N:18]3[CH2:19][CH2:20][O:21][CH2:22][CH2:23]3)[CH:7]=2)(=[O:34])=[O:33])=[CH:28][CH:27]=1
Reactant: COc1ncc(C#Cc2c(C)ncnc2N2CCOCC2)cc1N
Reactant: O=S(=O)(Cl)c1ccc(Cl)cc1
Solvent: c1ccncc1
Solvent: ClCCl
Solvent: O
Product: COc1ncc(C#Cc2c(C)ncnc2N2CCOCC2)cc1NS(=O)(=O)c1ccc(Cl)cc1
Temperature: 25 °C

Procedure:
To 100 mg (0.31 mmol) 2-Methoxy-5-(4-methyl-6-morpholin-4-yl-pyrimidin-5-ylethynyl)-pyridin-3-ylamine (E-9) in 5 mL DCM is added 130 mg (0.61 mmol) 4-chlorobenzenesulfonyl chloride and 72 μL (0.97 mmol) pyridine and the reaction mixture is stirred over night at RT. Water (2 mL) is added, the mixture is shaken for five minutes, the aqueous phase is separated and is extracted three times with 4 mL DCM. The combined organic phases are dried over MgSO4 and concentrated under reduced pressure. The crude product is purified by RP chromatography (C18, 20-80% ACN in water containing 1% formic acid). Yield: 105 mg (76%). HPLC-MS: M+H=500; tR=0.91 min.
Reaction SMILES: Br[C:2]1[CH:11]=[CH:10][C:5]2[NH:6][C:7](=[O:9])[NH:8][C:4]=2[CH:3]=1.[N+:12]([C:15]1[CH:16]=[C:17](B(O)O)[CH:18]=[CH:19][CH:20]=1)([O-:14])=[O:13]>>[N+:12]([C:15]1[CH:20]=[C:19]([C:2]2[CH:11]=[CH:10][C:5]3[NH:6][C:7](=[O:9])[NH:8][C:4]=3[CH:3]=2)[CH:18]=[CH:17][CH:16]=1)([O-:14])=[O:13]
Reactant: O=c1[nH]c2ccc(Br)cc2[nH]1
Reactant: O=[N+]([O-])c1cccc(B(O)O)c1
Product: O=c1[nH]c2ccc(-c3cccc([N+](=O)[O-])c3)cc2[nH]1

Procedure:
Prepared from 5-bromo-1,3-dihydro-benzoimidazol-2-one and 3-nitro-phenyl boronic acid in the same fashion as that of Example 5. White solid: mp 324-325° C.; 1H-NMR(DMSO-d6) δ10.8 (s, 2H), 8.4 (m, 1H), 8.15 (d, 1H, J=7.5 Hz), 8.1 (d, 1H, J=7.5 Hz), 7.7 (t, 1H, J=7.5 Hz), 7.35 (d, 1H, J=7.5 Hz), 7.3 (s, 1H), 7.05 (d, 1H, J=7.5 Hz); MS (ES) m/z 254 ([M−H]−, 100%); Anal. Calc. For C13H9N3O3: C, 61.18; H, 3.55; N, 16.46. Found: C, 60.5; H, 3.69; N, 15.53.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([C:12](=[S:14])[NH2:13])=[C:9]([CH3:11])[N:10]=2)[CH:7]=1.Cl[CH:16]([C:22](=O)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[C:17]([O:19][CH2:20][CH3:21])=[O:18]>CN(C=O)C>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([C:12]3[S:14][C:16]([C:17]([O:19][CH2:20][CH3:21])=[O:18])=[C:22]([C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)[N:13]=3)=[C:9]([CH3:11])[N:10]=2)[CH:7]=1
Reactant: CCOC(=O)C(Cl)C(=O)c1ccccc1
Reactant: Cc1nc2ccc(Br)cn2c1C(N)=S
Solvent: CN(C)C=O
Product: CCOC(=O)c1sc(-c2c(C)nc3ccc(Br)cn23)nc1-c1ccccc1
Temperature: 90 °C
Reaction time: 21 h
Yield: 65.5 %

Procedure:
To a suspension of 6-bromo-2-methylimidazo[1,2-a]pyridine-3-carbothioamide (700 mg, 2.59 mmol) obtained as described above in DMF (60 mL), was added ethyl 2-chloro-3-oxo-3-phenylpropanoate (1.76 g, 7.77 mmol), and the mixture was stirred at 90° C. for 21 h. The mixture was allowed to cool to rt, and the solvent was removed under reduced pressure. The residue was washed with water, EtOH and diethyl ether to give the titled compound (750 mg, 66%) as a pale yellow solid.
Reaction SMILES: [CH2:1]([C:4]1[N:5]([O:17][CH2:18][C:19]([NH2:21])=[O:20])[C:6]2[C:15]3[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=3[N:9]=[CH:8][C:7]=2[N:16]=1)[CH2:2][CH3:3].ClC1C=C(C=CC=1)C(OO)=[O:27].C1COCC1>ClCCl>[O-:27][N+:9]1[C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][C:15]=2[C:6]2[N:5]([O:17][CH2:18][C:19]([NH2:21])=[O:20])[C:4]([CH2:1][CH2:2][CH3:3])=[N:16][C:7]=2[CH:8]=1
Reactant: CCCc1nc2cnc3ccccc3c2n1OCC(N)=O
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: ClCCl
Solvent: C1CCOC1
Product: CCCc1nc2c[n+]([O-])c3ccccc3c2n1OCC(N)=O
Temperature: 0 °C
Reaction time: 1 h

Procedure:
A solution of 2-[(2-propyl-1H-imidazo[4,5-c]quinolin-1-yl)oxy]acetamide (2.7 g, 9.5 mmol) in dichloromethane (100 mL) was cooled to approximately 0° C., and 3-chloroperoxybenzoic acid (3.2 g of approximately 77% pure material, 14 mmol) was added. The reaction was stirred for ten minutes at 0° C. and for one hour at room temperature. An analysis by LC/MS indicated that no reaction had occurred; the starting material was very insoluble. THF (40 mL) was added, and the reaction was stirred for 23 hours. An analysis by LC/MS indicated the presence of starting material, and dichloromethane (500 mL) was added. The reaction was stirred for seven hours, was allowed to stand for three days, and then was concentrated under reduced pressure to provide 2-[(5-oxido-2-propyl-1H-imidazo[4,5-c]quinolin-1-yl)oxy]acetamide.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([SH:8])[CH:5]=[CH:6][CH:7]=1.C[S:10]([CH3:12])=O.O>[Cl-].[Na+].O>[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([S:8][S:10][C:12]2[CH:3]=[C:2]([CH:7]=[CH:6][CH:5]=2)[NH2:1])[CH:3]=1
Reactant: Nc1cccc(S)c1
Reactant: CS(C)=O
Agent: [Cl-]
Agent: [Na+]
Solvent: O
Product: Nc1cccc(SSc2cccc(N)c2)c1
Yield: 97.6 %

Procedure:
A solution of 3-aminobenzenethiol (0.85 mL, 8.0 mmol) in dimethyl sulfoxide (0.57 mL, 8.0 mmol) was heated at 85° C. for 4 h. The reaction mixture was poured into a solution of brine (25 mL) and water (25 mL) and extracted with ethyl acetate (100 mL). The organic layer was separated and washed with brine (25 mL), dried over anhydrous sodium sulfate, filtered, and evaporated to a crude oil. This material was purified by flash column chromatography to give the desired product (0.97 g, 98%) as a yellow oil. LCMS for C12H13N2S2 (M+H)+: m/z=249.0.
Reaction SMILES: C([O:3][C:4]([C:6]1[N:10]=[C:9]([C:11]2[CH:16]=[CH:15][N:14]=[CH:13][C:12]=2[NH:17][C:18]2[CH:23]=[CH:22][C:21]([I:24])=[CH:20][C:19]=2[F:25])[O:8][N:7]=1)=O)C.C1COCC1>C(Cl)Cl.CO>[F:25][C:19]1[CH:20]=[C:21]([I:24])[CH:22]=[CH:23][C:18]=1[NH:17][C:12]1[CH:13]=[N:14][CH:15]=[CH:16][C:11]=1[C:9]1[O:8][N:7]=[C:6]([CH2:4][OH:3])[N:10]=1
Reactant: CCOC(=O)c1noc(-c2ccncc2Nc2ccc(I)cc2F)n1
Solvent: C1CCOC1
Solvent: ClCCl
Solvent: CO
Product: OCc1noc(-c2ccncc2Nc2ccc(I)cc2F)n1
Reaction time: 8 h
Yield: 71.3 %

Procedure:
To a solution of 5-[3-(2-Fluoro-4-iodo-phenylamino)-pyridin-4-yl]-[1,2,4]oxadiazole-3-carboxylic acid ethyl ester (768 mg, 1.69 mmL, 1 eq) in THF (6 mL) LiBH4 (55 mg, 2.54 mmol, 1.5 eq) was added. The reaction mixture was stirred overnight and the solvent was evaporated. The residue was dissolved in EtOAc, washed with brine, and dried with anhydrous MgSO4. Filtration and removal of the solvent afforded the crude product which was subjected to silica gel column chromatography (eluent:CH2Cl2:MeOH 70:1) to give rise to pure product (497 mg). [5.01 min; 413 (M+1)]
Reaction SMILES: C(OC([N:8]1[CH2:13][CH2:12][CH2:11][CH2:10][C@@H:9]1[C:14]1[O:18][N:17]=[C:16]([C:19]2[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=2)[N:15]=1)=O)(C)(C)C.[F:27][C:28]([F:33])([F:32])[C:29]([OH:31])=[O:30]>>[F:27][C:28]([F:33])([F:32])[C:29]([OH:31])=[O:30].[CH3:26][O:25][C:22]1[CH:21]=[CH:20][C:19]([C:16]2[N:15]=[C:14]([C@H:9]3[CH2:10][CH2:11][CH2:12][CH2:13][NH:8]3)[O:18][N:17]=2)=[CH:24][CH:23]=1
Reactant: COc1ccc(-c2noc([C@H]3CCCCN3C(=O)OC(C)(C)C)n2)cc1
Solvent: O=C(O)C(F)(F)F
Product: COc1ccc(-c2noc([C@H]3CCCCN3)n2)cc1

Procedure:
Crude material from step 2 was treated with neat trifluoroacetic acid (TFA) at room temperature for 1 h. The TFA was evaporated. The crude product not further characterized.
Reaction SMILES: [F:1][C:2]1[CH:42]=[C:41]([N+:43]([O-])=O)[CH:40]=[CH:39][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][N:8]=[C:7]2[CH:11]=[C:12]([C:14]3[CH:38]=[CH:37][C:17]([CH2:18][N:19]([CH2:27][CH2:28][O:29][CH2:30][CH2:31][O:32][CH2:33][CH2:34][O:35][CH3:36])[C:20](=[O:26])[O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[CH:16][CH:15]=3)[S:13][C:6]=12.[Cl-].[NH4+]>CO.O.[Fe]>[NH2:43][C:41]1[CH:40]=[CH:39][C:3]([O:4][C:5]2[CH:10]=[CH:9][N:8]=[C:7]3[CH:11]=[C:12]([C:14]4[CH:38]=[CH:37][C:17]([CH2:18][N:19]([CH2:27][CH2:28][O:29][CH2:30][CH2:31][O:32][CH2:33][CH2:34][O:35][CH3:36])[C:20](=[O:26])[O:21][C:22]([CH3:25])([CH3:23])[CH3:24])=[CH:16][CH:15]=4)[S:13][C:6]=23)=[C:2]([F:1])[CH:42]=1
Reactant: COCCOCCOCCN(Cc1ccc(-c2cc3nccc(Oc4ccc([N+](=O)[O-])cc4F)c3s2)cc1)C(=O)OC(C)(C)C
Agent: [Fe]
Agent: [Cl-]
Agent: [NH4+]
Solvent: CO
Solvent: O
Product: COCCOCCOCCN(Cc1ccc(-c2cc3nccc(Oc4ccc(N)cc4F)c3s2)cc1)C(=O)OC(C)(C)C
Yield: 88.2 %

Procedure:
To a solution of 365 (0.49 g, 0.76 mmol) in MeOH (100 mL) was added iron dust (0.43 g, 7.6 mmol) and ammonium chloride (0.12 g, 2.3 mmol) in water (5 mL). The resulting mixture was heated to reflux for 4 h, then cooled, filtered through a celite pad and concentrated. The residue was partitioned between dichloromethane and water; the organic phase was collected, washed with brine, dried over anhydrous magnesium sulfate, filtered, and concentrated. The residue was purified by silica gel chromatography (eluent 2% MeOH in EtOAc) to give 366 (0.41 g, 88% yield). LRMS (M+H): 612.6
Reaction SMILES: Br[C:2]1[N:6]2[CH2:7][CH2:8][N:9]([CH2:12][C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([C:19]([F:22])([F:21])[F:20])[C:14]=3[Cl:23])[C:10](=[O:11])[C:5]2=[N:4][N:3]=1.[F:24][C:25]1[CH:30]=[CH:29][C:28](B(O)O)=[CH:27][CH:26]=1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.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>[Cl:23][C:14]1[C:15]([C:19]([F:22])([F:21])[F:20])=[CH:16][CH:17]=[CH:18][C:13]=1[CH2:12][N:9]1[CH2:8][CH2:7][N:6]2[C:2]([C:28]3[CH:29]=[CH:30][C:25]([F:24])=[CH:26][CH:27]=3)=[N:3][N:4]=[C:5]2[C:10]1=[O:11]
Reactant: O=C1c2nnc(Br)n2CCN1Cc1cccc(C(F)(F)F)c1Cl
Reactant: OB(O)c1ccc(F)cc1
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: C1COCCO1
Product: O=C1c2nnc(-c3ccc(F)cc3)n2CCN1Cc1cccc(C(F)(F)F)c1Cl
Temperature: 100 °C
Yield: 46.1 %

Procedure:
To a solution of 3-bromo-7-(2-chloro-3-(trifluoromethyl)benzyl)-6,7-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-8(5H)-one (100 mg, 0.24 mmol) and 4-fluorophenylboronic acid (40 mg, 0.27 mmol) in dioxane (0.6 mL) was added 1M Na2CO3 (0.6 mL). The flask was purged with nitrogen for 10 minutes and Pd(PPh3)4 (14 mg, 0.012 mmol) was added at once. The flask was purged with nitrogen for an additional 5 minutes and then heated at 100° C. for 18 h. After cooling to rt, brine was added, and the mixture was extracted with EtOAc (×3). The combined organic extracts were dried (Na2SO4), filtered, and concentrated to give a brown solid. Purification by chromatography (SiO2; hexanes—100% EtOAc) afforded the desired product as a white solid (47 mg, 45%). MS (ESI): mass calcd. for C19H13ClF4N4O, 424.1; m/z found, 425.1 [M+H]+. 1H NMR (500 MHz, DMSO-d6) δ 7.91-7.73 (m, 4H), 7.59-7.54 (m, 1H), 7.49-7.43 (m, 2H), 4.89 (s, 2H), 4.56-4.42 (m, 2H), 3.92-3.84 (m, 2H).
Reaction SMILES: C[O:2][C:3](=[O:26])[C:4]1[CH:9]=[CH:8][C:7]([C:10]#[C:11][C:12]2[CH:13]=[C:14]3[C:19](=[CH:20][CH:21]=2)[O:18][CH2:17][CH2:16][C:15]3([CH2:23][O:24][CH3:25])[CH3:22])=[CH:6][CH:5]=1.[OH-].[Na+]>C1COCC1.C(O)C>[CH3:25][O:24][CH2:23][C:15]1([CH3:22])[C:14]2[C:19](=[CH:20][CH:21]=[C:12]([C:11]#[C:10][C:7]3[CH:6]=[CH:5][C:4]([C:3]([OH:26])=[O:2])=[CH:9][CH:8]=3)[CH:13]=2)[O:18][CH2:17][CH2:16]1
Reactant: COCC1(C)CCOc2ccc(C#Cc3ccc(C(=O)OC)cc3)cc21
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Solvent: C1CCOC1
Product: COCC1(C)CCOc2ccc(C#Cc3ccc(C(=O)O)cc3)cc21
Reaction time: 18 h
Yield: 91 %

Procedure:
625 mg (1.78 mmol) of 4-(4-methoxymethyl-4-methyl-chroman-6-ylethynyl)-benzoic acid methyl ester was dissolved in 9 ml of THF/ethanol (1/1) and treated with 2.34 ml of 3N NaOH (4 eq.). The reaction flask was kept in the dark and stirring continued for 18 h at room temperature. The mixture was then poured onto crushed ice/ HCl, extracted twice with diethylether, the organic phase was washed with water, dried over magnesium sulfate, filtrated and the solvent was evaporated. Crystallization from ethylacetate yielded 545 mg of the title product as white crystals of m.p. 202-203° C.
Reaction SMILES: [N:1]1([CH2:7][CH2:8][CH2:9][OH:10])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[N+:11]([C:14]1[CH:19]=[CH:18][C:17](O)=[CH:16][CH:15]=1)([O-:13])=[O:12].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>O1CCCC1>[N+:11]([C:14]1[CH:19]=[CH:18][C:17]([O:10][CH2:9][CH2:8][CH2:7][N:1]2[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]2)=[CH:16][CH:15]=1)([O-:13])=[O:12]
Reactant: O=[N+]([O-])c1ccc(O)cc1
Reactant: OCCCN1CCCCC1
Agent: CC(C)OC(=O)N=NC(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: O=[N+]([O-])c1ccc(OCCCN2CCCCC2)cc1
Temperature: 25 °C
Reaction time: 40 h

Procedure:
3-piperidin-1-yl-propan-1-ol (3.66 g, 25.6 mmol), 4-nitrophenol (2.96 g, 21.3 mmol) and triphenylphosphine (6.71 g, 25.6 mmol) were dissolved in dry tetrahydrofuran in a current of nitrogen, and cooled on the ice bath. Diisopropyl azodicarboxylate (5.0 mL, 25.6 mmol) was dripped in, and stirred at room temperature for 40 hours. The reaction liquid was concentrated, diethyl ether was added, and the solid precipitate was filtered off. The filtrate was concentrated, the product purified by silica gel column chromatography (chloroform/methanol=100/0-95/5), and the target substance (3.49 g, 62%) was thus obtained as a light yellow oily residue.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[CH2:9][N:10]1[C:14](=[O:15])[C:13]([CH3:17])([CH3:16])[CH2:12][O:11]1.[N+:18]([O-])([O-:20])=[O:19].[K+]>S(=O)(=O)(O)O>[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([N+:18]([O-:20])=[O:19])=[CH:4][C:3]=1[CH2:9][N:10]1[C:14](=[O:15])[C:13]([CH3:17])([CH3:16])[CH2:12][O:11]1
Reactant: O=[N+]([O-])[O-]
Reactant: CC1(C)CON(Cc2ccc(F)cc2Cl)C1=O
Agent: O=S(=O)(O)O
Agent: [K+]
Product: CC1(C)CON(Cc2cc([N+](=O)[O-])c(F)cc2Cl)C1=O
Yield: 50.8 %

Procedure:
By the method of Example 3, Step A, 20 g (0.078 mole) of 2-[(2-chloro-4-fluorophenyl)methyl]-4,4-dimethyl-3-isoxazolidinone, 7.8 g (0.78 mole) of potassium nitrate, and 100 ml of concentrated sulfuric acid were reacted, yielding 12 g of 2-[(2-chloro-4-fluoro-5-nitrophenyl)methyl]-4,4-dimethyl-3-isoxazolidinone as a light yellow solid. Passage through a column of silica gel was omitted since the product was crystalline. Purification was accomplished by recrystallization from ethyl acetate/hexane. This reaction was repeated, and the products were combined.
Reaction SMILES: [C:1]([O:5][C@@H:6]([C:10]1[C:19]([CH3:20])=[CH:18][C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11]=1[C:21]1[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][CH:22]=1)[C:7]([OH:9])=[O:8])([CH3:4])([CH3:3])[CH3:2].C1[C:33](=O)[N:32](Br)[C:30](=O)C1.CC(N=NC(C#N)(C)C)(C#N)C.C(Cl)Cl>C(Cl)(Cl)(Cl)Cl>[C:1]([O:5][C@@H:6]([C:10]1[C:19]([CH2:20][N:32]([CH3:33])[CH3:30])=[CH:18][C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11]=1[C:21]1[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][CH:22]=1)[C:7]([OH:9])=[O:8])([CH3:4])([CH3:2])[CH3:3]
Reactant: O=C1CCC(=O)N1Br
Reactant: Cc1cc2ccccc2c(-c2ccc(Cl)cc2)c1[C@H](OC(C)(C)C)C(=O)O
Agent: CC(C)(C#N)N=NC(C)(C)C#N
Solvent: ClCCl
Solvent: ClC(Cl)(Cl)Cl
Product: CN(C)Cc1cc2ccccc2c(-c2ccc(Cl)cc2)c1[C@H](OC(C)(C)C)C(=O)O
Temperature: 25 °C
Yield: 268.3 %

Procedure:
Preparation of(S)-ethyl 2-(3-(bromomethyl)-1-(4-chlorophenyl)naphthalen-2-yl)-2-tert-butoxyacetate: To a solution of (S)-ethyl 2-tert-butoxy-2-(1-(4-chlorophenyl)-3-methylnaphthalen-2-yl)acetate (3K, 43 mg, 0.0105 mmol) in CCl4 (2 mL) was added NBS (24 mg, 0.13 mmol) and AIBN (cat. amount). The reaction mixture was refluxed for 5 h. After cooling to room temperature, the reaction mixture was diluted by DCM, washed with sat. NaHCO3, extracted with DCM and the organic layers were combined and dried over MgSO4, filtered, concentrated and purified by flash column chromatography (silica gel, ethyl acetate/hexanes) to provide 12 mg of the desired product. 1H-MNR 400 MHz (CDCl3) δ: 8.01 (s, 1H), 7.77 (d, J=4 Hz, 1H), 7.43-7.15 (m, 7H), 5.11 (d, J=5.2 Hz, 1H), 5.06 (s, 1H), 5.00 (d, J=5.2 Hz, 1H), 4.07-4.02 (m, 2H), 1.20-1.15 (m, 3H), 0.96 (s, 9H).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:13]=[CH:12][C:11]([CH:14]([S:16]([CH2:18][C:19]([OH:21])=[O:20])=[O:17])[CH3:15])=[CH:10][CH:9]=1.CI.[C:24](=O)([O-])[O-].[K+].[K+]>CS(C)=O>[CH3:24][O:20][C:19](=[O:21])[CH2:18][S:16]([CH:14]([C:11]1[CH:12]=[CH:13][C:8]([C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=2[Cl:1])=[CH:9][CH:10]=1)[CH3:15])=[O:17]
Reactant: O=C([O-])[O-]
Reactant: CC(c1ccc(-c2ccccc2Cl)cc1)S(=O)CC(=O)O
Agent: [K+]
Solvent: CI
Solvent: CS(C)=O
Product: COC(=O)CS(=O)C(C)c1ccc(-c2ccccc2Cl)cc1
Temperature: 25 °C
Reaction time: 19 h

Procedure:
A solution of 19.9 gm (0.059 mol) of [1-(2'-chloro-4-biphenylyl)-ethylsulfinyl]-acetic acid and 12.5 gm (0.088 mol) of methyl iodide in 120 ml of dry dimethyl sulfoxide was admixed with 12.2 gm (0.088 mol) of dry potassium carbonate, and the mixture was stirred at room temperature for 19 hours. The crude reaction product was precipitated with water and extracted with ethyl acetate (yield: 23.1. gm). For purification, the obtained crude product was purified by chromatography on 1200 gm of silicagel with cyclohexane ethyl acetate = 1/1. The combined fractions with an Rf -value of 0.23 (on carrier 2) were combined and evaporated, leaving 6.2 gm (31.2% of theory) of the title compound; oil, Rf -value: 0.23 on carrier 1 with cyclohexane/ethyl acetate = 1/1.
Reaction SMILES: C(O[SiH](OCC)OCC)C.[C:11]1([CH2:17][CH2:18][C:19](=[O:21])[CH3:20])[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.[OH-].[Na+]>CC(C)[O-].[Y+3].CC(C)[O-].CC(C)[O-].C1COCC1>[C:11]1([CH2:17][CH2:18][CH:19]([OH:21])[CH3:20])[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1
Reactant: CC(=O)CCc1ccccc1
Agent: CC(C)[O-]
Agent: CCO[SiH](OCC)OCC
Agent: [Na+]
Solvent: C1CCOC1
Product: CC(O)CCc1ccccc1
Temperature: 60 °C
Reaction time: 0.5 h

Procedure:
A dry Schlenk tube under argon was charged with 37 mg (0.15 mmol) of yttrium (III) isopropoxide (Y5O(iPrO)13). Triethoxysilane (1.4 mL, 7.5 mmol) was added, and the reaction mixture was heated to 60° C. After 0.5 hours, 4-phenyl-2-butanone (450 μL, 3 mmol) was added. After 24 hours, the reaction was complete, as determined by GLC analysis of a aliquot taken from the reaction mixture. THF (8 mL) and aqueous NaOH (1 N, 15 mL) were added, and the mixture was stirred vigorously for 12 hours. After work-up as in Example 13, the crude material was purified by flash chromatography (ether:hexane=3:7) to afford 235 mg (of 4-phenyl-2-butanol (>93% pure by 1H-NMR analysis, 48% adjusted yield).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11](=[C:14]([Br:29])[C:15]2[CH:20]=[CH:19][C:18]([C:21]([N:23]3[CH2:28][CH2:27]O[CH2:25][CH2:24]3)=[O:22])=[CH:17][CH:16]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].N1CCCC[CH2:31]1>>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11](=[C:14]([Br:29])[C:15]2[CH:20]=[CH:19][C:18]([C:21]([N:23]3[CH2:24][CH2:25][CH2:31][CH2:27][CH2:28]3)=[O:22])=[CH:17][CH:16]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)N1CCC(=C(Br)c2ccc(C(=O)N3CCOCC3)cc2)CC1
Reactant: C1CCNCC1
Product: CC(C)(C)OC(=O)N1CCC(=C(Br)c2ccc(C(=O)N3CCCCC3)cc2)CC1

Procedure:
Same procedure as described for the preparation of compound 82, but using piperidine in place of morpholine.