Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([N:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)[N:5]=[C:4]([N:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)[N:3]=1.[C:20]([C:22]1[CH:27]=[CH:26][C:25](B(O)O)=[CH:24][CH:23]=1)#[N:21]>>[O:17]1[CH2:18][CH2:19][N:14]([C:4]2[N:5]=[C:6]([N:8]3[CH2:13][CH2:12][O:11][CH2:10][CH2:9]3)[N:7]=[C:2]([C:25]3[CH:26]=[CH:27][C:22]([C:20]#[N:21])=[CH:23][CH:24]=3)[N:3]=2)[CH2:15][CH2:16]1
Reactant: Clc1nc(N2CCOCC2)nc(N2CCOCC2)n1
Reactant: N#Cc1ccc(B(O)O)cc1
Product: N#Cc1ccc(-c2nc(N3CCOCC3)nc(N3CCOCC3)n2)cc1
Yield: 50 %

Procedure:
The title compound was prepared by following the procedure of example 473 step 2 using 4,4′-(6-chloro-1,3,5-triazine-2,4-diyl)dimorpholine and 4-cyanophenyl-boronic acid. Yield 86 mg, 50% yield; HPLC: Rt=2.60 min; MS 353 [M+H].
Reaction SMILES: [CH2:1]([OH:4])[CH2:2][OH:3].[OH-].[K+].[C:7](#[N:10])[CH:8]=[CH2:9].Cl>O>[CH2:8]([C:7]#[N:10])[CH2:9][O:3][CH2:2][CH2:1][O:4][CH2:9][CH2:8][C:7]#[N:10]
Reactant: C=CC#N
Reactant: OCCO
Agent: Cl
Agent: [K+]
Agent: [OH-]
Solvent: O
Product: N#CCCOCCOCCC#N
Reaction time: 8 h

Procedure:
To a 5 liter double walled (for water cooling) glass reactor with a bottom drain and stopcock was charged 930 grams (15 moles) of ethylene glycol and 45.6 grams of 40% aqueous KOH solution. Some 1620 grams (30.6 moles) of acrylonitrile (NC--CH=CH2) were then added dropwise with stirring at such a rate that the temperature was kept below 35° C. After the addition was completed the mixture was stirred an additional hour and then allowed to stand overnight. The mixture was then neutralized to a pH of 7 by the addition of 6 molar HCl. After washing with saturated NaCl solution three times, the product was separated from the aqueous layer, dried over CaCl2 and passed through an Al2O3 column to insure that all basic materials had been removed. The yield obtained was 90% of theoretical.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][CH2:9][C:10]1[CH:11]=[C:12]([C:18]2[CH:19]=[C:20]([CH:25]=[CH:26][CH:27]=2)[C:21](OC)=[O:22])[CH:13]=[CH:14][C:15]=1[O:16][CH3:17])=[O:7])([CH3:4])([CH3:3])[CH3:2].[BH4-].[Li+].Cl>O1CCCC1>[OH:22][CH2:21][C:20]1[CH:19]=[C:18]([C:12]2[CH:13]=[CH:14][C:15]([O:16][CH3:17])=[C:10]([CH:11]=2)[CH2:9][NH:8][C:6](=[O:7])[O:5][C:1]([CH3:4])([CH3:3])[CH3:2])[CH:27]=[CH:26][CH:25]=1
Reactant: COC(=O)c1cccc(-c2ccc(OC)c(CNC(=O)OC(C)(C)C)c2)c1
Agent: Cl
Agent: [BH4-]
Agent: [Li+]
Solvent: C1CCOC1
Product: COc1ccc(-c2cccc(CO)c2)cc1CNC(=O)OC(C)(C)C
Temperature: 25 °C
Yield: 81.8 %

Procedure:
Methyl 3-(3-{[(t-butoxycarbonyl)amino]-methyl}-4-methoxyphenyl)benzoate (1.943 g) was dissolved in 30 ml of tetrahydrofuran, 250 mg of lithium borohydride was added thereto, and the mixture was stirred at room temperature for 2 weeks. 1N Hydrochloric acid was added to the reaction mixture which was then extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was removed. The residue was purified by silica gel column, to give 1.47 g of the title compound in the 3:1→1:1 hexane-ethyl acetate fraction.
Reaction SMILES: [CH2:1]([C:4]1[CH:5]=[C:6]([CH:9]=[C:10]([O:13][CH3:14])[C:11]=1[OH:12])[CH:7]=[O:8])[CH:2]=[CH2:3].C(=O)([O-])[O-].[K+].[K+].Br[CH2:22][CH2:23][CH2:24][CH3:25]>O>[CH2:1]([C:4]1[CH:5]=[C:6]([CH:9]=[C:10]([O:13][CH3:14])[C:11]=1[O:12][CH2:22][CH2:23][CH2:24][CH3:25])[CH:7]=[O:8])[CH:2]=[CH2:3]
Reactant: C=CCc1cc(C=O)cc(OC)c1O
Reactant: CCCCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Product: C=CCc1cc(C=O)cc(OC)c1OCCCC
Yield: 98.8 %

Procedure:
A mixture of 3-allyl-4-hydroxy-5-methoxybenzaldehyde (10.25 g, 0.053 mole), dimethylformanide (150 ml), potassium carbonate (8.29 g, 0.06 mole) and 1-bromobutane (8.22 g, 0.06 mole) was maintained at 40°-45° C. for three hours. The reaction mixture was plunged into iced water and the oil formed extracted with dichloromethane. After washing with water, drying and evaporation of the solvent, a brown oil was obtained which was passed through a bed of silica 60 to give a pale yellow oil, 3-allyl-4-butoxy-5-methoxybenzaldehyde (13 g, yield=91%).
Reaction SMILES: [F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].FC(F)(F)C(O)=O.[Cl:15][C:16]1[CH:17]=[N:18][C:19]2[NH:20][C:21]3[CH:22]=[CH:23][CH:24]=[C:25]([CH:38]=3)[CH2:26][CH2:27][C:28]3[CH:36]=[C:32]([NH:33][C:34]=1[N:35]=2)[CH:31]=[C:30]([NH2:37])[CH:29]=3.[CH3:39][N:40]1[CH:44]=[CH:43][C:42]([C:45](Cl)=[O:46])=[N:41]1>>[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[Cl:15][C:16]1[CH:17]=[N:18][C:19]2[NH:20][C:21]3[CH:22]=[CH:23][CH:24]=[C:25]([CH:38]=3)[CH2:26][CH2:27][C:28]3[CH:36]=[C:32]([NH:33][C:34]=1[N:35]=2)[CH:31]=[C:30]([NH:37][C:45]([C:42]1[CH:43]=[CH:44][N:40]([CH3:39])[N:41]=1)=[O:46])[CH:29]=3
Reactant: Cn1ccc(C(=O)Cl)n1
Reactant: Nc1cc2cc(c1)Nc1nc(ncc1Cl)Nc1cccc(c1)CC2
Solvent: O=C(O)C(F)(F)F
Product: Cn1ccc(C(=O)Nc2cc3cc(c2)Nc2nc(ncc2Cl)Nc2cccc(c2)CC3)n1
Yield: 47 %

Procedure:
The desired compound was prepared according to the procedure of Example B26, using 6-chloro-2,4,8,22-tetraazatetracyclo[14.3.1.1(3,7).1(9,13)]docosa-1(20),3(22),4,6,9(21),10,12,16,18-nonaen-11-amine bis(trifluoroacetate) and 1-methyl-1H-pyrazole-3-carbonyl chloride as the starting materials in 47% yield. LCMS for C23H21ClN7O (M+H)+: m/z=446.2. 1H NMR (400 MHz, DMSO-d6): δ 9.93 (s, 1H), 9.76 (s, 1H), 9.70 (s, 1H), 8.20 (s, 1H), 7.88 (m, 1H), 7.82 (d, 1H), 7.64 (m, 1H), 7.42 (m, 1H), 7.36 (m, 1H), 7.11 (dd, 1H), 6.87 (m, 2H), 6.73 (d, 1H), 3.94 (s, 3H), 2.86 (m, 4H).
Reaction SMILES: [Cl:1][C:2]1[CH:14]=[CH:13][C:12]2[C:11]3[C:6](=[CH:7][C:8]([Cl:15])=[CH:9][CH:10]=3)[CH2:5][C:4]=2[CH:3]=1.Br[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22]>>[Cl:1][C:2]1[CH:14]=[CH:13][C:12]2[C:11]3[C:6](=[CH:7][C:8]([Cl:15])=[CH:9][CH:10]=3)[C:5]([CH2:13][CH2:14][CH2:2][CH2:3][CH2:4][CH3:12])([CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22])[C:4]=2[CH:3]=1
Reactant: CCCCCCBr
Reactant: Clc1ccc2c(c1)Cc1cc(Cl)ccc1-2
Product: CCCCCCC1(CCCCCC)c2cc(Cl)ccc2-c2ccc(Cl)cc21
Yield: 91 %

Procedure:
2,7-Dichloro-9,9-di(1-hexyl)fluorene was prepared from 2,7-dichlorofluorene and 1-bromohexane following the procedure of Example 1 as colorless crystals (recrystallized from hexane) in 91 percent yield; melting point 66° C. to 67° C. HPLC analysis showed that the sample was 99 percent or greater pure and the spectral data confirmed the title structure.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:12][C:11]([CH3:13])=[C:10]([C:14]3[C:15](=[O:21])[CH2:16][CH2:17][C:18]=3[O:19][CH3:20])[CH:9]=2)=[CH:4][CH:3]=1.C([N-]C(C)C)(C)C.[Li+].[O:30]1[CH2:35][CH2:34][CH:33]([CH:36]=[O:37])[CH2:32][CH2:31]1>O1CCCC1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:12][C:11]([CH3:13])=[C:10]([C:14]3[C:15](=[O:21])[CH:16]([CH:36]([OH:37])[CH:33]4[CH2:34][CH2:35][O:30][CH2:31][CH2:32]4)[CH2:17][C:18]=3[O:19][CH3:20])[CH:9]=2)=[CH:4][CH:3]=1
Reactant: COC1=C(c2cc(-c3ccc(Cl)cc3)sc2C)C(=O)CC1
Reactant: O=CC1CCOCC1
Agent: CC(C)[N-]C(C)C
Agent: [Li+]
Solvent: C1CCOC1
Product: COC1=C(c2cc(-c3ccc(Cl)cc3)sc2C)C(=O)C(C(O)C2CCOCC2)C1
Temperature: 78 °C
Reaction time: 0.5 h
Yield: 84.3 %

Procedure:
To a solution of 2-[5-(4-Chloro-phenyl)-2-methyl-thiophen-3-yl]-3-methoxy-cyclopent-2-enone (255 mg, 0.8 mmol) in anhydrous tetrahydrofuran (6 ml) at −78° C. under an atmosphere of nitrogen was added lithium diisopropylamide (1.8M in THF/heptanes/ethylbenzene; 0.49 ml, 0.89 mmol) dropwise over a period of 5 minutes and the reaction allowed to stir at 78° C. for 30 minutes. A solution of tetrahydro-pyran-4-carbaldehyde (102 mg, 0.89 mmol) in anhydrous tetrahydrofuran (1 ml) was then added dropwise over a period of 5 minutes before the reaction was allowed to warm to room temperature and stirred for a further 30 minutes. The reaction was quenched by the addition of saturated aqueous ammonium chloride solution (50 ml) and extracted with ethyl acetate (50 ml) and the organic later separated, dry loaded onto silica and purified by flash chromatography to give 2-[5-(4-Chloro-phenyl)-2-methyl-thiophen-3-yl]-5-[hydroxy-(tetrahydro-pyran-4-yl)-methyl]-3-methoxy-cyclopent-2-enone (292 mg).
Reaction SMILES: [NH2:1][C@@H:2]([CH2:5][CH3:6])[CH2:3][OH:4].[C:7](=O)([O:13]C(C)(C)C)[O:8][C:9]([CH3:12])([CH3:11])[CH3:10].C(N(CC)CC)C>C1COCC1>[OH:4][CH2:3][C@@H:2]([NH:1][C:7](=[O:13])[O:8][C:9]([CH3:12])([CH3:11])[CH3:10])[CH2:5][CH3:6]
Reactant: CC[C@H](N)CO
Reactant: CC(C)(C)OC(=O)OC(C)(C)C
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: CC[C@@H](CO)NC(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 3 h

Procedure:
To a solution of (S)-2-aminobutan-1-ol (1 eq) in THF (0.26 M) at 0° C. was added di-tert-butyl carbonate (1 eq) and triethylamine (1 eq). The reaction was stirred at room temperature for 3 hours. The reaction mixture was concentrated en vaccuo; and the residue was diluted in ethyl acetate. The organic solution was washed with water (2×), brine, dried over anhydrous MgSO4, and concentrated en vaccuo. The material was carried onto the next step without further purification.
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]2)=[CH:5][CH:4]=1)#[CH:2].[I:15]I.S([O-])([O-])=O.[Na+].[Na+]>C1COCC1.[H-].[Cl-].C1([Zr+2]C2CC=CC=2)CC=CC=1>[I:15]/[CH:2]=[CH:1]/[C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]2)=[CH:5][CH:4]=1
Reactant: C#Cc1ccc(N2CCCCC2)cc1
Reactant: II
Agent: C1=CCC([Zr+2]C2=CC=CC2)=C1
Agent: O=S([O-])[O-]
Agent: [Cl-]
Solvent: C1CCOC1
Product: I/C=C/c1ccc(N2CCCCC2)cc1
Reaction time: 1 h
Yield: 52.3 %

Procedure:
1-(4-Ethynylphenyl)piperidine (3.49 g, 18.8 mmol) in dry THF (100 mL) was added to a suspension of bis(cyclopentdienyl)zirconium(IV)chloride hydride (5.09 g, 19.76 mmol) in THF (50 mL) at r.t. under nitrogen in the dark. After 1 h, iodine (3.65 g, 23.7 mmol) was added. After a further 2 h, saturated aqueous sodium sulfite (50 mL) was carefully added and the reaction mixture was partitioned between water (30 mL) and EtOAc (100 mL). The organic layer was separated and dried (MgSO4), filtered and concentrated. Purification by column chromatography (5% EtOAc in PE) gave the title compound (3.08 g, 52%) as a colorless-solid. 1H NMR (CDCl3) 1.61 (2H, m), 1.70 (4H, m), 3.20 (4H, m), 6.54 (1H, d), 6.83 (2H, d), 7.19 (2H, d), 7.31 (1H, d).
Reaction SMILES: [CH2:1]([C:8]1[CH:16]=[CH:15][CH:14]=[C:13]2[C:9]=1[CH2:10][CH2:11][C:12]2=[O:17])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cr](O)(O)(=O)=[O:19].S(=O)(=O)(O)O.C(=O)([O-])[O-].[K+].[K+]>O.C(O)(=O)C>[C:1]([C:8]1[CH:16]=[CH:15][CH:14]=[C:13]2[C:9]=1[CH2:10][CH2:11][C:12]2=[O:17])(=[O:19])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=[Cr](=O)(O)O
Reactant: O=C1CCc2c(Cc3ccccc3)cccc21
Agent: O=C([O-])[O-]
Agent: O=S(=O)(O)O
Agent: [K+]
Solvent: CC(=O)O
Solvent: O
Product: O=C1CCc2c1cccc2C(=O)c1ccccc1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
In 100 ml. of acetic acid is dissolved 11.1 g. of 4-benzyl indan-1-one, followed by the addition of 13.4 g. of chromic acid and 2.5 ml. of concentrated sulfuric acid. The mixture is stirred at room temperature for 2 hours, after which it is poured into 4 l. of water. After 200 g. of anhydrous potassium carbonate is added, the mixture is extracted with chloroform. The organic layer is washed with water and dried over anhydrous magnesium sulfate. The solvent is distilled off under reduced pressure and the oily residue is purified by column chromatography on silica gel with chloroform as the eluent and, then, recrystallized from cyclohexane. The procedure gives 4-benzoylindan-1-one melting at 87°-89° C.
Reaction SMILES: [C:1]([N:5]1[C:9]([C:10]2[CH:15]=[CH:14][C:13]([Cl:16])=[CH:12][CH:11]=2)=[CH:8][C:7]([CH2:17][CH2:18][CH:19]=O)=[N:6]1)([CH3:4])([CH3:3])[CH3:2].[F:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=1[N:28]1[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]1.CCN(C(C)C)C(C)C.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>>[C:1]([N:5]1[C:9]([C:10]2[CH:15]=[CH:14][C:13]([Cl:16])=[CH:12][CH:11]=2)=[CH:8][C:7]([CH2:17][CH2:18][CH2:19][N:31]2[CH2:30][CH2:29][N:28]([C:23]3[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=3[F:21])[CH2:33][CH2:32]2)=[N:6]1)([CH3:4])([CH3:3])[CH3:2]
Reactant: Fc1ccccc1N1CCNCC1
Reactant: CC(C)(C)n1nc(CCC=O)cc1-c1ccc(Cl)cc1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: CCN(C(C)C)C(C)C
Product: CC(C)(C)n1nc(CCCN2CCN(c3ccccc3F)CC2)cc1-c1ccc(Cl)cc1

Procedure:
105 mg (78%) of target compound was obtained by using a method same as in Example 1 by using 3-(1-tert-butyl-5-(4-chlorophenyl)-1H-pyrazol-3-yl)propanal (80 mg, 0.275 mmol), 1-(2-fluorophenyl)piperazine (50 mg, 0.275 mmol), DIPEA (0.072 mL, 0.413 mmol) and NaBH(OAc)3 (175 mg, 0.825 mmol).
Reaction SMILES: [S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]1[CH:11]=[CH:10][N:9]=[C:8]2[N:12]([C@@H:15]3[O:23][C@H:22]([CH2:24][OH:25])[C@@H:17]([O:18][C:19](=[O:21])[CH3:20])[CH2:16]3)[CH:13]=[N:14][C:7]=12.[C:26]([O:29]C(=O)C)(=[O:28])[CH3:27]>N1C=CC=CC=1>[S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]1[CH:11]=[CH:10][N:9]=[C:8]2[N:12]([C@@H:15]3[O:23][C@H:22]([CH2:24][OH:25])[C@@H:17]([O:18][C:19](=[O:21])[CH3:20])[C@H:16]3[O:29][C:26](=[O:28])[CH3:27])[CH:13]=[N:14][C:7]=12
Reactant: CC(=O)OC(C)=O
Reactant: CC(=O)O[C@H]1C[C@H](n2cnc3c(-c4cccs4)ccnc32)O[C@@H]1CO
Solvent: c1ccncc1
Product: CC(=O)O[C@@H]1[C@H](OC(C)=O)[C@@H](CO)O[C@H]1n1cnc2c(-c3cccs3)ccnc21
Temperature: 25 °C
Reaction time: 12 h
Yield: 74.9 %

Procedure:
Compound 9 (247 mg, 0.4 mmol) was azeotroped with pyridine, followed by addition of pyridine (4 ml) and acetic anhydride (75 μl, 0.8 mmol). After stirring at room temperature for 12 hours, the reaction mixture was partitioned between ethyl acetate and 5% aqueous NaHCO3, and the organic layer was washed with 5% aqueous NaHCO3. This organic layer was dried over anhydrous sodium sulfate, concentrated and azeotroped with toluene. The residue was then dissolved in methylene chloride (40 ml). To this reaction mixture, dichloroacetic acid (400 μl) was added at 0° C. and stirred for 15 minutes at 0° C. The reaction mixture was partitioned with 5% aqueous NaHCO3, and the organic layer was washed with 5% aqueous NaHCO3. After drying over anhydrous sodium sulfate, the organic layer was concentrated and purified on a silica gel column to give Compound 13 (125 mg, 87%).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:11]3([C:15](=[O:16])[N:14]([CH3:17])[C:13](SC)=[N:12]3)[CH2:10][CH:9]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[F:26])[O:8][C:5]2=[CH:6][CH:7]=1.[NH4+:27].[I-]>N.CCO>[NH2:27][C:13]1[N:14]([CH3:17])[C:15](=[O:16])[C:11]2([C:4]3[C:5](=[CH:6][CH:7]=[C:2]([Br:1])[CH:3]=3)[O:8][CH:9]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[F:26])[CH2:10]2)[N:12]=1
Reactant: [NH4+]
Reactant: CSC1=NC2(CC(c3ccccc3F)Oc3ccc(Br)cc32)C(=O)N1C
Agent: N
Agent: [I-]
Solvent: CCO
Product: CN1C(=O)C2(CC(c3ccccc3F)Oc3ccc(Br)cc32)N=C1N
Yield: 70.3 %

Procedure:
A solution of 6-bromo-2-(2-fluorophenyl)-1′-methyl-2′-(methylthio)spiro-[chroman-4,4′-imidazol]-5′(1′H)-one (80 mg, 0.183 mmol) and NH4I (53.21 mg, 0.367 mmol) in NH3/EtOH (2 mL, 1.5 N) was heated at 110° C. in a tube in a microwave reactor for 3 h. After cooling, the mixture was concentrated in vacuo to give a residue, which was purified by preparative TLC to afford 2′-amino-6-bromo-2-(2-fluorophenyl)-1′-methylspiro-[chroman-4,4′-imidazol]-5′(1′H)-one (52 mg, 70%).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH:9]([C:11]2[CH:16]=[CH:15][C:14]([F:17])=[CH:13][C:12]=2[O:18][C:19]([F:24])([F:23])[CH:20]([F:22])[F:21])[OH:10])[CH:5]=[CH:6][C:7]=1[F:8]>ClCCl.O=[Mn]=O>[Br:1][C:2]1[CH:3]=[C:4]([C:9]([C:11]2[CH:16]=[CH:15][C:14]([F:17])=[CH:13][C:12]=2[O:18][C:19]([F:23])([F:24])[CH:20]([F:21])[F:22])=[O:10])[CH:5]=[CH:6][C:7]=1[F:8]
Reactant: OC(c1ccc(F)c(Br)c1)c1ccc(F)cc1OC(F)(F)C(F)F
Agent: O=[Mn]=O
Solvent: ClCCl
Product: O=C(c1ccc(F)c(Br)c1)c1ccc(F)cc1OC(F)(F)C(F)F
Reaction time: 6 h
Yield: 60 %

Procedure:
To a solution of 1-bromo-3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)benzene (5.0 g, 17 mmol) in ether (40 mL) at −78° C. was added a solution of n-butyllithium (6.9 mL, 2.5 M, 17 mmol). The reaction mixture was stirred for 15 minutes and was added a solution of 3-bromo-4-fluorobenzaldehyde (3.5 g, 17 mmol) in ether (10 mL). The reaction was stirred at −78° C. for 2 h, then quenched with sat. NH4Cl and warmed to room temperature. The ether layer was separated and dried over magnesium sulfate, filtered and concentrated to yield (3-bromo-4-fluorophenyl)(4-fluoro-2-(1,1,2,2-tetrafluoroethoxy)phenyl)methanol as an amber oil (6.5 g, 92% yield). The product was used in the next step without further purification. To a solution of (3-bromo-4-fluorophenyl)(4-fluoro-2-(1,1,2,2-tetrafluoroethoxy)phenyl)methanol (29.5 g, 71.3 mmol) in dichloromethane (600 mL) was added MnO2 (30 g, 345 mmol). The reaction mixture was stirred for 6 h, then another 30 g of MnO2 was added and the reaction continued to stir overnight. The MnO2 addition was repeated twice and the reaction was stirred for a total of 48 h when the reaction was complete. The suspension was filtered through a pad of celite, the filtrate vas concentrated and the residue was purified by ISCO flash chromatography to yield (3-bromo-4-fluorophenyl)(4-fluoro-2-(1,1,2,2-tetrafluoroethoxy)phenyl)methanone as a yellow oil (60% yield). 1H NMR (400 MHz, CDCl3) δ ppm 8.06 (1H, d, J=6.59 Hz), 7.76 (1H, ddd, J=6.48, 4.50, 2.20 Hz), 7.38-7.44 (2H, m), 7.21-7.29 (2H, m), 6.09-5.83 (1 H, t).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:22]=[C:23]([O:27][CH3:28])[C:24]=1[O:25][CH3:26])[C:6]([N:8]1[CH2:12][CH2:11][C:10]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)([CH2:13][CH2:14][OH:15])[CH2:9]1)=[O:7].[CH3:29][S:30](Cl)(=[O:32])=[O:31]>>[CH3:28][O:27][C:23]1[CH:22]=[C:5]([CH:4]=[C:3]([O:2][CH3:1])[C:24]=1[O:25][CH3:26])[C:6]([N:8]1[CH2:12][CH2:11][C:10]([C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=2)([CH2:13][CH2:14][O:15][S:30]([CH3:29])(=[O:32])=[O:31])[CH2:9]1)=[O:7]
Reactant: COc1cc(C(=O)N2CCC(CCO)(c3ccccc3)C2)cc(OC)c1OC
Reactant: CS(=O)(=O)Cl
Product: COc1cc(C(=O)N2CCC(CCOS(C)(=O)=O)(c3ccccc3)C2)cc(OC)c1OC

Procedure:
Prepare by the method of Example 2.5.2 using 1-(3,4,5-trimethoxybenzoyl)-3-phenyl-3-(2-hydroxyethyl)pyrrolidine (prepared from (−)-3-phenyl-3-(2-hydroxyethyl)pyrrolidine (R,R)-di-p-anisoyltartaric acid salt) (2.21 g, 5.51 mmol) and methanesulfonyl chloride (0.7 mL, 9.0 mmol) to give the title compound: Rf=0.47 (silica gel, ethyl acetate).
Reaction SMILES: [CH3:1][C:2]1[CH2:7][CH2:6][C@@H:5]([C:8]([CH3:10])=[CH2:9])[CH2:4][CH:3]=1.C1N(CCCS(O)(=O)=O)CC[O:13]C1>>[CH3:1][C:2]1[C:7](=[O:13])[CH2:6][CH:5]([C:8]([CH3:10])=[CH2:9])[CH2:4][CH:3]=1
Reactant: O=S(=O)(O)CCCN1CCOCC1
Reactant: C=C(C)[C@H]1CC=C(C)CC1
Product: C=C(C)C1CC=C(C)C(=O)C1
Reaction time: 1 h

Procedure:
For transformation of limonene 50 mg Pleurotus sapidus mycel was placed in 1.5 mL MOPS buffer (0.1 M; pH 7.0) and the dried cell mass was rehydrated for one hour at 200 rpm and 24° C. For producing carvone 41 mM limonene were directly applied to the rehydrated culture. The reaction took place for 24 h at 150 rpm and 24° C. After addition of the internal standard (for example camphor for limonene transformation) samples were extracted with 2 mL azeotropic pentane/ether mixture, centrifuged and dried over night with Na2SO4.
Reaction SMILES: [CH:1]1([C:6]2([CH2:26][CH2:27][C:28]3[CH:42]=[CH:41][C:31]([CH2:32][NH:33]C(=O)OC(C)(C)C)=[C:30]([CH2:43][CH3:44])[CH:29]=3)[CH2:11][C:10]([OH:12])=[C:9]([CH2:13][C:14]3[N:24]=[C:17]4[N:18]=[C:19]([CH3:23])[CH:20]=[C:21]([CH3:22])[N:16]4[N:15]=3)[C:8](=[O:25])[O:7]2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[ClH:45]>ClCCl.O1CCOCC1>[ClH:45].[NH2:33][CH2:32][C:31]1[CH:41]=[CH:42][C:28]([CH2:27][CH2:26][C:6]2([CH:1]3[CH2:2][CH2:3][CH2:4][CH2:5]3)[O:7][C:8](=[O:25])[C:9]([CH2:13][C:14]3[N:24]=[C:17]4[N:18]=[C:19]([CH3:23])[CH:20]=[C:21]([CH3:22])[N:16]4[N:15]=3)=[C:10]([OH:12])[CH2:11]2)=[CH:29][C:30]=1[CH2:43][CH3:44]
Reactant: CCc1cc(CCC2(C3CCCC3)CC(O)=C(Cc3nc4nc(C)cc(C)n4n3)C(=O)O2)ccc1CNC(=O)OC(C)(C)C
Agent: Cl
Solvent: ClCCl
Solvent: C1COCCO1
Product: CCc1cc(CCC2(C3CCCC3)CC(O)=C(Cc3nc4nc(C)cc(C)n4n3)C(=O)O2)ccc1CN
Yield: 96 %

Procedure:
tert-Butyl 4-(2-{2-cyclopentyl-5-[(5,7-dimethyl[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)methyl]-4-hydroxy-6-oxo-3,6-dihydro-2H-pyran-2-yl}ethyl)-2-ethylbenzylcarbamate (35 mg, 0.06 mmol, example A(126)) was dissolved in dichloromethane (1 mL) and 4N HCl in dioxane (0.5 mL) and stirred at room temperature 2 h. The solution was concentrated to give an off-white solid (30 mg, 96%). 1H NMR (300 MHz, CDCl3): δ ppm 1.14 (t, J=7.54 Hz, 3 H) 1.37–1.49 (m, 1 H) 1.52–1.66 (m, 6 H), 1.67–1.77 (m, 2 H) 2.05–2.16 (m, 2 H) 2.58 (s, 4 H) 2.60–2.70 (m, 6 H) 2.74–2.80 (m, 1 H), 3.80 (d, J=14.51 Hz, 2 H) 4.02 (q, J=5.78 Hz, 2 H) 7.07 (s, 1 H) 7.13 (s, 1 H) 7.16–7.21 (m, 1 H) 7.32 (d, J=7.72 Hz, 1 H) 8.15 (s, 3 H). MS (ESI): 504 (M+H)+.
Reaction SMILES: [NH2:1][C:2]1[CH:19]=[CH:18][C:5]([O:6][C:7]2[C:16]3[N:15]=[CH:14][C:13](=[O:17])[NH:12][C:11]=3[N:10]=[CH:9][CH:8]=2)=[CH:4][C:3]=1[F:20].[C:21]([C:25]1[CH:29]=[C:28]([N:30]=[C:31]=[O:32])[N:27]([C:33]2[CH:38]=[CH:37][C:36]([S:39]([CH3:42])(=[O:41])=[O:40])=[CH:35][CH:34]=2)[N:26]=1)([CH3:24])([CH3:23])[CH3:22].C(Cl)Cl>>[C:21]([C:25]1[CH:29]=[C:28]([NH:30][C:31]([NH:1][C:2]2[CH:19]=[CH:18][C:5]([O:6][C:7]3[C:16]4[N:15]=[CH:14][C:13](=[O:17])[NH:12][C:11]=4[N:10]=[CH:9][CH:8]=3)=[CH:4][C:3]=2[F:20])=[O:32])[N:27]([C:33]2[CH:38]=[CH:37][C:36]([S:39]([CH3:42])(=[O:41])=[O:40])=[CH:35][CH:34]=2)[N:26]=1)([CH3:24])([CH3:22])[CH3:23]
Reactant: Nc1ccc(Oc2ccnc3[nH]c(=O)cnc23)cc1F
Reactant: CC(C)(C)c1cc(N=C=O)n(-c2ccc(S(C)(=O)=O)cc2)n1
Solvent: ClCCl
Product: CC(C)(C)c1cc(NC(=O)Nc2ccc(Oc3ccnc4[nH]c(=O)cnc34)cc2F)n(-c2ccc(S(C)(=O)=O)cc2)n1
Yield: 41 %

Procedure:
Method F2 was used with 8-(4-amino-3-fluorophenoxy)pyrido[2,3-b]pyrazin-3(4H)-one (56 mg, 0.206 mmol) and a 0.1 M solution of 3-tert-butyl-5-isocyanato-1-(4-(methylsulfonyl)phenyl)-1H-pyrazole in CH2Cl2 (5.8 mL, 0.58 mmol). The title compound was obtained as a yellow solid in 41% yield (50 mg) after chromatography on a Biotage 25+M column.
Reaction SMILES: [O:1]1[CH:5]=[CH:4][N:3]=[CH:2]1.[Li]CCCC.I[C:12]1[CH:13]=[C:14]([C:22]([O:24][CH3:25])=[O:23])[CH:15]=[C:16]([CH:21]=1)[C:17]([O:19][CH3:20])=[O:18]>C1COCC1.CCOC(C)=O.O.[Cl-].[Cl-].[Zn+2].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>[O:1]1[CH:5]=[CH:4][N:3]=[C:2]1[C:12]1[CH:21]=[C:16]([C:17]([O:19][CH3:20])=[O:18])[CH:15]=[C:14]([CH:13]=1)[C:22]([O:24][CH3:25])=[O:23]
Reactant: c1cocn1
Reactant: COC(=O)c1cc(I)cc(C(=O)OC)c1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [Cl-]
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Solvent: O
Product: COC(=O)c1cc(C(=O)OC)cc(-c2ncco2)c1
Temperature: 0 °C
Yield: 54 %

Procedure:
To a stirred solution of oxazole ((0.28 mL, 4.2 mmol) in THF (10 mL) at −78° C. was added nBuLi (2.8 mL 1.6 N solution in hexane, 4.4 mmol). ZnCl2 (20 mL 0.5M soln, 10 mmol) was added after 30 min and the reaction mixture was warmed up to 0° C. for 1 h. To the resulting mixture was added dimethyl 5-iodoisophthalate (1.28 g, 4.0 mmol) and Pd(PPh3)4 and was heated at reflux for 5 h. The reaction mixture was cooled to room temperature and diluted with EtOAc and H2O. The layers were separated and the organic layer was washed with, brine, dried with Na2SO4 and concentrated under reduced pressure. The residue was purified by column chromatography (20% EtOAc in hexanes) to provide dimethyl 5-(oxazol-2-yl)isophthalate (568 mg, 54%).