Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[C:10]2[CH:11]=[CH:12][C:13]([O:15][C:16]3[CH:21]=[CH:20][N:19]=[C:18](Cl)[N:17]=3)=[CH:14][C:9]=2[O:8][N:7]=1)=[O:5])[CH3:2].C([O-])([O-])=O.[Cs+].[Cs+].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.[C:71]([O:75][C:76](=[O:78])[NH2:77])([CH3:74])([CH3:73])[CH3:72]>O1CCOCC1.O.CCOC(C)=O>[CH2:1]([O:3][C:4]([C:6]1[C:10]2[CH:11]=[CH:12][C:13]([O:15][C:16]3[CH:21]=[CH:20][N:19]=[C:18]([NH:77][C:76]([O:75][C:71]([CH3:74])([CH3:73])[CH3:72])=[O:78])[N:17]=3)=[CH:14][C:9]=2[O:8][N:7]=1)=[O:5])[CH3:2]
Reactant: CCOC(=O)c1noc2cc(Oc3ccnc(Cl)n3)ccc12
Reactant: CC(C)(C)OC(N)=O
Agent: CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CCOC(C)=O
Solvent: O
Solvent: C1COCCO1
Product: CCOC(=O)c1noc2cc(Oc3ccnc(NC(=O)OC(C)(C)C)n3)ccc12
Temperature: 110 °C
Reaction time: 4.5 h

Procedure:
A solution of 1.4 g (4.3 mMol) 6-(2-chloro-pyrimidin-4-yloxy)-benzo[d]isoxazole-3-carboxylic acid ethyl ester (Step 4.1) in 32 ml dioxane is degassed repeatedly by evaporation and flushing with N2. Then 2.1 g (6.44 mMol) Cs2CO3, 77 mg (0.13 mMol) 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene, 39.3 mg (0.0429 mMol) tris(dibenzylidenaceton)dipalladium(0) and 603 mg (5.15 mMol) carbamic acid tert-butyl ester are added successively. After 4.5 h stirring at 110° C., the mixture is cooled to rt and another 77 mg 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene, 39.7 mg tris(dibenzylidenaceton)dipalladium(0), 603 mg carbamic acid tert-butyl ester and 2.1 g Cs2CO3 are added and stirring is continued for 5 h. Then the cooled mixture is poured into EtOAc and water, the aq. layer separated off and extracted with EtOAc. The organic layers are washed with water and brine, dried (Na2SO4) and concentrated together with 8 g SiO2. The resulting powder is put on top of a chromatography column (SiO2; CH2Cl2) and the title compound eluted with CH2Cl2→CH2Cl2/EtOAc 4:1: MS: [M+1]+=401; HPLC: tRet=15.4.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[C:4]([CH:9]([O:11][C:12]2[CH:17]=[CH:16][C:15]([N+:18]([O-])=O)=[CH:14][C:13]=2[F:21])[CH3:10])[C:3]=1[Cl:22]>CO.[Pt]=O>[F:21][C:13]1[CH:14]=[C:15]([CH:16]=[CH:17][C:12]=1[O:11][CH:9]([C:4]1[C:5]([Cl:8])=[CH:6][CH:7]=[C:2]([Cl:1])[C:3]=1[Cl:22])[CH3:10])[NH2:18]
Reactant: CC(Oc1ccc([N+](=O)[O-])cc1F)c1c(Cl)ccc(Cl)c1Cl
Agent: O=[Pt]
Solvent: CO
Product: CC(Oc1ccc(N)cc1F)c1c(Cl)ccc(Cl)c1Cl

Procedure:
3-Fluoro-4-[1-(2,3,6-trichlorophenyl)ethoxy]aniline was prepared according to the method described in Example 20e but from 0.093 g of platinum oxide and 1.5 g of 1,2,4-trichloro-3-[1-(2-fluoro-4-nitrophenoxy)ethyl]benzene in 100 cm3 of methanol.
Reaction SMILES: C([O:3][P:4]([CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][C:17]([F:29])([F:28])[C:18]([F:27])([F:26])[C:19]([F:25])([F:24])[C:20]([F:23])([F:22])[F:21])([O:6]CC)=[O:5])C.Br[Si](C)(C)C>ClCCl>[P:4]([CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][C:17]([F:28])([F:29])[C:18]([F:26])([F:27])[C:19]([F:24])([F:25])[C:20]([F:21])([F:22])[F:23])([OH:5])([OH:6])=[O:3]
Reactant: CCOP(=O)(CCCCCCCCC(F)(F)C(F)(F)C(F)(F)C(F)(F)F)OCC
Agent: C[Si](C)(C)Br
Solvent: ClCCl
Product: O=P(O)(O)CCCCCCCCC(F)(F)C(F)(F)C(F)(F)C(F)(F)F
Temperature: 25 °C
Reaction time: 18 h
Yield: 75.6 %

Procedure:
To a solution of 7.03 g of 1-(diethylphosphono)-8-(nonafluorobutyl)octane in 30 mL of dichloromethane was added 6.12 g of bromotrimethylsilane. After 18 hr at room temperature, the solution was concentrated to a pale yellow liquid, and the intermediate silylphosphonate ester was dissolved in 150 mL of methanol. The resultant solution was stirred at room temperature for 30 min and concentrated to a white solid. Dissolution in methanol and concentration were repeated two times, and two recrystallizations of the crude product from acetonitrile gave 4.68 g of 1-phosphono-8-(nonafluorobutyl)octane (CF3(CF2)3(CH2)8PO3H2) as white crystals, m.p. 87-89° C.
Reaction SMILES: [C:1]1([CH:7]2[CH2:12][CH2:11][CH:10]([NH2:13])[CH2:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH2:14]([C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([CH2:22][CH3:23])[C:17]=1[N:24]=[C:25]=[O:26])[CH3:15].N1C=CC=CC=1.Cl>ClCCl>[CH2:14]([C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([CH2:22][CH3:23])[C:17]=1[NH:24][C:25]([NH:13][CH:10]1[CH2:9][CH2:8][CH:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[CH2:12][CH2:11]1)=[O:26])[CH3:15]
Reactant: NC1CCC(c2ccccc2)CC1
Reactant: CCc1cccc(CC)c1N=C=O
Agent: Cl
Solvent: c1ccncc1
Solvent: ClCCl
Product: CCc1cccc(CC)c1NC(=O)NC1CCC(c2ccccc2)CC1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a solution of 1 g of 4-phenylcyclohexylamine in 10 ml of dichloromethane was added 2,6-diethylphenylisocyanate dropwise in the presence of pyridine and the mixture was stirred for 2 hours at room temperature. To the resultant mixture was added 30 ml of diluted hydrochloric acid and the solution was extracted with chloroform. The extract was washed with water, aqueous sodium hydrogencarbonate solution and saturated brine, and then dried over magnesium sulfate. The solvent was distilled away and the residue was crystallized from methanol to give 0.4 g of N-(2,6-diethylphenyl)-N'-(4-phenylcyclohexyl)urea, melting at 247°-249° C.
Reaction SMILES: [CH3:1][C:2]([NH:4][C:5]1[C:10]([I:11])=[C:9]([NH:12][C:13]([CH3:15])=[O:14])[C:8]([I:16])=[C:7]([C:17]([O-:19])=[O:18])[C:6]=1[I:20])=[O:3].[Na+].Br[CH2:23][CH2:24][CH2:25][CH2:26][C:27]([O:29][CH2:30][CH3:31])=[O:28].O>CN(C=O)C>[C:13]([NH:12][C:9]1[C:8]([I:16])=[C:7]([C:6]([I:20])=[C:5]([NH:4][C:2](=[O:3])[CH3:1])[C:10]=1[I:11])[C:17]([O:19][CH2:23][CH2:24][CH2:25][CH2:26][C:27]([O:29][CH2:30][CH3:31])=[O:28])=[O:18])(=[O:14])[CH3:15]
Reactant: CCOC(=O)CCCCBr
Reactant: CC(=O)Nc1c(I)c(NC(C)=O)c(I)c(C(=O)[O-])c1I
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: CCOC(=O)CCCCOC(=O)c1c(I)c(NC(C)=O)c(I)c(NC(C)=O)c1I
Temperature: 25 °C
Reaction time: 12 h
Yield: 97.3 %

Procedure:
To a stirred solution of sodium diatrizoate (59.0 g, 92.8 mmol) in 350 ml of dry DMF was added ethyl 5-bromovalerate (14.7 ml, 92.8 mmol) in two portions and the resulting solution was stirred at ambient temperature for 12 hr. The reaction mixture was poured into 3.5 1 of water and the resulting white precipitate was collected, washed with ether and then air dried. The crude product was dissolved in acetonitrile-ethanol (5:2), filtered through a pad of silica gel and the filtrate was evaporated to give a solid (67 g, 97%). Recrystallization from methanol-water gave analytically pure product (mp 237°-239° C.) after drying under high vacuum; CI-MS: MH+ 743. The 1H-NMR (300 MHz) spectral data was consistent with the desired product. Calculated for C18H21I3N2O6 ; C 29.13, H 2.85, I 51.30; Found: C 29.13, H 2.78, I 51.15, N 3.75.
Reaction SMILES: Br[C:2]1[N:7]=[C:6]([C:8]2[N:12]3[CH:13]=[CH:14][C:15]([C:17]([F:20])([CH3:19])[CH3:18])=[N:16][C:11]3=[N:10][CH:9]=2)[CH:5]=[CH:4][CH:3]=1.CC1(C)C(C)(C)OB([C:29]2[CH:36]=[CH:35][CH:34]=[CH:33][C:30]=2[C:31]#[N:32])O1>>[F:20][C:17]([C:15]1[CH:14]=[CH:13][N:12]2[C:8]([C:6]3[N:7]=[C:2]([C:29]4[CH:36]=[CH:35][CH:34]=[CH:33][C:30]=4[C:31]#[N:32])[CH:3]=[CH:4][CH:5]=3)=[CH:9][N:10]=[C:11]2[N:16]=1)([CH3:19])[CH3:18]
Reactant: CC1(C)OB(c2ccccc2C#N)OC1(C)C
Reactant: CC(C)(F)c1ccn2c(-c3cccc(Br)n3)cnc2n1
Product: CC(C)(F)c1ccn2c(-c3cccc(-c4ccccc4C#N)n3)cnc2n1
Yield: 37 %

Procedure:
The product of Example 25 (0.34 g, 1.0 mmol) was coupled to 2-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)benzonitrile following the procedure in Example 2 to give 2-{6-[7-(1-fluoro-1-methyl-ethyl)imidazo[1,2-α]pyrimidin-3-yl]pyridin-2-yl}benzonitrile (0.133 g, 37%) as a white solid: δH (360 MHz, CDCl3) 1.80 (6H, d, J 22), 7.38 (1H, dd, J 7 and 2), 7.59 (1H, ddd, J 8, 7 and 1), 7.75 (1H, ddd, J 8, 7 and 1), 7.80-7.96 (5H, m), 8.38 (1H, s), 10.36 (1H, d, J 7); m/z (ES+) 358 (M++H).
Reaction SMILES: [O:1]1[CH2:6][CH:5]=[C:4]([C:7]2[CH:12]=[CH:11][C:10]([N:13]3[CH2:17][C@H:16]([C:18]([NH2:20])=[O:19])[O:15][C:14]3=[O:21])=[CH:9][C:8]=2[F:22])[CH2:3][CH2:2]1.[H][H]>CO.[Pd]>[O:1]1[CH2:6][CH2:5][CH:4]([C:7]2[CH:12]=[CH:11][C:10]([N:13]3[CH2:17][C@H:16]([C:18]([NH2:20])=[O:19])[O:15][C:14]3=[O:21])=[CH:9][C:8]=2[F:22])[CH2:3][CH2:2]1
Reactant: [H][H]
Reactant: NC(=O)[C@H]1CN(c2ccc(C3=CCOCC3)c(F)c2)C(=O)O1
Agent: [Pd]
Solvent: CO
Product: NC(=O)[C@H]1CN(c2ccc(C3CCOCC3)c(F)c2)C(=O)O1

Procedure:
A mixture of (5R)-(−)-3-[4-(3,6-dihydro-2H-pyran-4-yl)-3-fluorophenyl]-2-oxo-5-oxazolidinecarboxamide (EXAMPLE 9, Step 2, 200 mg, 0.653 mmol) and 10% palladium-on-carbon (139 mg, 0.131 mmol) in methanol (26 mL) is shaken under a 40 psi hydrogen atmosphere on a Parr apparatus for 5 h. The catalyst is then removed by filtration through a pad of Celite, and the filtrate is concentrated under reduced pressure and chromatographed on a Flash 40S 40 g silica gel (32-63 μm) cartridge, eluting with a gradient of methanol/methylene chloride (2/98-3/97). Pooling and concentration of those fractions with an Rf=0.37 by TLC (methanol/chloroform, 2×5/95) gives the title compound, mp 153-156° C.; MS (ESI−) for C15H17N2O4F m/z 307 (M−H); [α]25D=−21 (c 0.87, DMSO).
Reaction SMILES: [CH2:1]([C:3]1([CH3:13])[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[NH:5][C:4]1=[O:12])[CH3:2].Cl[CH2:15][CH2:16][O:17]C1CCCCO1>>[CH2:1]([C:3]1([CH3:13])[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]([CH2:15][CH2:16][OH:17])[C:4]1=[O:12])[CH3:2]
Reactant: ClCCOC1CCCCO1
Reactant: CCC1(C)C(=O)Nc2ccccc21
Product: CCC1(C)C(=O)N(CCO)c2ccccc21

Procedure:
Prepared from 3-ethyl-3-methyl-1,3-dihydro-2H-indol-2-one (prepared by the method of Endler and Becker; Organic Syntheses Coll. vol. 4 page 657) and 2-(2-chloroethoxy) tetrahydro-2H-pyran.
Reaction SMILES: C([O:8][C:9]1[CH:14]=[CH:13][C:12]([N:15]2[CH2:19][CH2:18][CH2:17][C:16]2=[O:20])=[CH:11][CH:10]=1)C1C=CC=CC=1.ClCCl.CO>C1COCC1.C(O)(=O)C.[Pd]>[OH:8][C:9]1[CH:14]=[CH:13][C:12]([N:15]2[CH2:19][CH2:18][CH2:17][C:16]2=[O:20])=[CH:11][CH:10]=1
Reactant: O=C1CCCN1c1ccc(OCc2ccccc2)cc1
Agent: [Pd]
Solvent: ClCCl
Solvent: CC(=O)O
Solvent: CO
Product: O=C1CCCN1c1ccc(O)cc1
Reaction time: 5 h
Yield: 66.4 %

Procedure:
6.2 g (23.2 mmol) 1-(4-benzyloxy-phenyl)-pyrrolidin-2-one is dissolved in 200 ml THF. 3 drops of acetic acid are added and the solution is hydrogenated for 5 hours at RT and normal pressure in presence of 0.62 g palladium 10% on charcoal. Filtration and concentration gives a semisolid material. Chromatography (silica gel, dichloromethane/methanol 95:5) yields 2.73 g (66%) of a brownish solid. MS: m/e=175.9 (M−H).
Reaction SMILES: ClC1C=CC(COC2C=NNC(=O)C=2)=NC=1.[F:17][C:18]1[CH:19]=[CH:20][C:21]([CH2:24][O:25][C:26]2[CH:31]=[N:30][N:29](C3CCCCO3)[C:28](=[O:38])[CH:27]=2)=[N:22][CH:23]=1>>[F:17][C:18]1[CH:19]=[CH:20][C:21]([CH2:24][O:25][C:26]2[CH:31]=[N:30][NH:29][C:28](=[O:38])[CH:27]=2)=[N:22][CH:23]=1
Reactant: O=c1cc(OCc2ccc(F)cn2)cnn1C1CCCCO1
Agent: O=c1cc(OCc2ccc(Cl)cn2)cn[nH]1
Product: O=c1cc(OCc2ccc(F)cn2)cn[nH]1

Procedure:
5-(5-Fluoro-pyridin-2-ylmethoxy)-2H-pyridazin-3-one is prepared following preparation 18b from 800 mg (2.62 mmol) 5-(5-fluoro-pyridin-2-ylmethoxy)-2-(tetrahydro-pyran-2-yl)-2H-pyridazin-3-one.
Reaction SMILES: [C:1]([C:5]1[CH:10]=[CH:9][C:8]([CH3:11])=[C:7]([NH2:12])[C:6]=1[NH2:13])([CH3:4])([CH3:3])[CH3:2].[C:14]1([CH:21]=[CH:20][C:18]([OH:19])=[CH:17][CH:16]=1)[OH:15].C1(C(=CC=CC=1)O)O.O=O.[OH-].[Na+]>C(OCCO)CC.OO.O.O.O.O.O.O.S([O-])([O-])(=O)=O.[Cu+2].C(O)(=O)C>[C:1]([C:5]1[CH:10]=[CH:9][C:8]([CH3:11])=[C:7]([NH2:12])[C:6]=1[NH2:13])([CH3:4])([CH3:2])[CH3:3].[C:18]1(=[O:19])[CH:20]=[CH:21][C:14](=[O:15])[CH:16]=[CH:17]1
Reactant: Oc1ccc(O)cc1
Agent: [Cu+2]
Agent: Cc1ccc(C(C)(C)C)c(N)c1N
Agent: O=O
Solvent: CCCOCCO
Solvent: CC(=O)O
Solvent: O
Product: O=C1C=CC(=O)C=C1
Reaction time: 0.25 h

Procedure:
About 3.56 g (0.02 mol) t-butyltoluenediamine was dissolved in about 30 mL ethyleneglycol monopropyl ether. About 2.4 mL glacial acetic acid was added followed by about 1.98 g (0.018 mol) hydroquinone, about 0.22 g (0.002 mol) catechol (chemical name 1,2-dihydroxybenzene), and about 0.2 g copper sulfate pentahydrate. About 10 drops of 1% hydrogen peroxide was added and oxygen was passed for about 5 hours, at a rate of about 40 cc/min. When the reaction was over, about 1.7 g sodium hydroxide, dissolved in about 3 mL of water was added and the mixture was stirred for about 15 min. Reaction product is obtained by pouring the reaction mixture into water and filtering the precipitated polymer and drying it in vacuo.
Reaction SMILES: [N+:1]([C:4]1[C:9]2[NH:10][C:11]([NH2:13])=[N:12][C:8]=2[CH:7]=[CH:6][CH:5]=1)([O-])=O.[CH:14]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH:17]=[C:16]([C:24](O)=[O:25])[N:15]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.CCN(C(C)C)C(C)C.C([O-])(O)=O.[Na+].O>[NH2:1][C:4]1[C:9]2[NH:10][C:11]([NH:13][C:24]([C:16]3[N:15]=[CH:14][C:23]4[C:18]([CH:17]=3)=[CH:19][CH:20]=[CH:21][CH:22]=4)=[O:25])=[N:12][C:8]=2[CH:7]=[CH:6][CH:5]=1
Reactant: Nc1nc2cccc([N+](=O)[O-])c2[nH]1
Reactant: O=C(O)c1cc2ccccc2cn1
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Agent: O=C([O-])O
Solvent: O
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: Nc1cccc2nc(NC(=O)c3cc4ccccc4cn3)[nH]c12
Temperature: 25 °C
Yield: 41.2 %

Procedure:
1.42 g (8 mmol) of above 7-nitro-1H-benzoimidazol-2-ylamine was reacted with 1.38 g (8 mmol) of isoquinoline-3-carboxylic acid, 3.4 g (9 mmol) of HBTU in 30.0 mL of DMF and 5.0 mL of DIEA as described in general procedure A. After cooling to room temperature, the reaction mixture was diluted with 60 mL of saturated NaHCO3 and 100 mL of water. The solid was collected by filtration and washed with water and dried under reduced pressure, and subsequently subjected to hydrogenation as described in general procedure C to give 1.0 g (41%) of the isoquinoline-3-carboxylic acid (7-amino-1H-benzoimidazol-2-yl)-amide. LCMS: 304 (M+1)+
Reaction SMILES: N[C:2]1[CH:7]=[C:6]([CH3:8])[C:5]([Br:9])=[CH:4][C:3]=1[CH3:10].[F:11][B-](F)(F)F.[H+].N([O-])=O.[Na+]>O>[Br:9][C:5]1[CH:4]=[C:3]([CH3:10])[C:2]([F:11])=[CH:7][C:6]=1[CH3:8]
Reactant: Cc1cc(Br)c(C)cc1N
Reactant: F[B-](F)(F)F
Agent: O=N[O-]
Agent: [H+]
Agent: [Na+]
Solvent: O
Product: Cc1cc(Br)c(C)cc1F
Reaction time: 1 h

Procedure:
373 g of 2-amino-5-bromo-p-xylene were suspended in 1860 ml of H2O in a 4 l four-necked flask, the mixture was cooled to 3° C. (internal temperature), and 612 ml of tetrafluoroboric acid were added. 154 g of NaNO2 in 300 ml of water were then added dropwise over the course of 60 minutes. After 60 minutes, the solid was filtered off with suction and washed with a little cold 5% tetrafluoroboric acid, then with a little cold methanol and finally with a little cold diethyl ether. The yellow solid (497 g=90%) was dried overnight in an oil-pump vacuum.
Reaction SMILES: [N:1]1([C:7]2[N:14]=[CH:13][CH:12]=[CH:11][C:8]=2[C:9]#[N:10])[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.[F:15][C:16]([F:32])([F:31])[C:17]1[O:21][N:20]=[C:19]([C:22]2[CH:23]=[C:24]([CH:28]=[CH:29][CH:30]=2)[C:25](O)=[O:26])[N:18]=1>>[F:31][C:16]([F:15])([F:32])[C:17]1[O:21][N:20]=[C:19]([C:22]2[CH:23]=[C:24]([CH:28]=[CH:29][CH:30]=2)[C:25]([N:4]2[CH2:3][CH2:2][N:1]([C:7]3[N:14]=[CH:13][CH:12]=[CH:11][C:8]=3[C:9]#[N:10])[CH2:6][CH2:5]2)=[O:26])[N:18]=1
Reactant: N#Cc1cccnc1N1CCNCC1
Reactant: O=C(O)c1cccc(-c2noc(C(F)(F)F)n2)c1
Product: N#Cc1cccnc1N1CCN(C(=O)c2cccc(-c3noc(C(F)(F)F)n3)c2)CC1
Yield: 81 %

Procedure:
This compound was synthesized from 2-(piperazin-1-yl)nicotinonitrile and 3-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)benzoic acid as described for example 37 step 3 (135 mg, yield 81%). 1H NMR (400 MHz, DMSO-d6) δ 8.45-8.43 (dd, J=4.8 Hz, 1.8 Hz, 1H), 8.18-8.15 (dd, J=7.3 Hz, 1.6 Hz, 1H), 8.13-8.10 (m, 2H), 7.78-7.71 (m, 2H), 6.99-6.96 (dd, J=7.5 Hz, 4.8 Hz, 1H), 3.81-3.75 (m, 4H), 3.63-3.54 (m, 4H). MS (ESI) m/z: Calculated for C20H15F3N6O2: 428.12. found: 429.1 (M+H)+
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][CH2:9][CH2:10][C:11]([OH:13])=[O:12].S(=O)(=O)(O)O.[CH3:19]O>>[OH:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][CH2:9][CH2:10][C:11]([O:13][CH3:19])=[O:12]
Reactant: O=C(O)CCCc1ccccc1O
Reactant: CO
Agent: O=S(=O)(O)O
Product: COC(=O)CCCc1ccccc1O

Procedure:
4-(2-Hydroxyphenyl)butyric acid (1 g, 5.55 mmol) was dissolved in 20 mL anhydrous methanol, and 5 mL sulfuric acid. The mixture was heated to reflux for 6 hours. After aqueous workup, 1.14 g of methyl 4-(2-hydroxyphenyl)butyrate was obtained. 1H NMR (CDCl3): 1.92 (q, 2H), 2.40 (t, 2H), 2.65 (t, 2H), 3.72 (s, 3H), 6.84 (m, 2H), 7.10 (m, 2H).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:29]=[C:30]([N:32]2[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]2)[CH:31]=1)[C:5]([NH:7][C:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11]([O:18][C:19]2[CH:24]=[CH:23][N:22]=[C:21](S(C)(=O)=O)[N:20]=2)=[CH:10][CH:9]=1)=[O:6].[CH3:38][S:39]([CH2:42][CH2:43][NH2:44])(=[O:41])=[O:40]>>[F:1][C:2]1[CH:3]=[C:4]([CH:29]=[C:30]([N:32]2[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]2)[CH:31]=1)[C:5]([NH:7][C:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11]([O:18][C:19]2[CH:24]=[CH:23][N:22]=[C:21]([NH:44][CH2:43][CH2:42][S:39]([CH3:38])(=[O:41])=[O:40])[N:20]=2)=[CH:10][CH:9]=1)=[O:6]
Reactant: CS(=O)(=O)CCN
Reactant: CS(=O)(=O)c1nccc(Oc2ccc(NC(=O)c3cc(F)cc(N4CCCCC4)c3)c3ccccc23)n1
Product: CS(=O)(=O)CCNc1nccc(Oc2ccc(NC(=O)c3cc(F)cc(N4CCCCC4)c3)c3ccccc23)n1

Procedure:
Compound is prepared from 3-fluoro-N-[4-(2-methanesulfonyl-pyrimidin-4-yloxy)-naphthalen-1-yl]-5-piperidin-1-yl-benzamide and 2-methanesulfonylethylamine according to conditions described in general procedure C. Mp: 102-104° C.; 1H NMR (400 MHz, CDCl3) δ 1.62-1.71 (m, 6 H), 2.54-2.64 (m, 5 H), 3.27 (t, J=5.5 Hz, 4 H), 3.50 (s, 2 H), 5.66 (bs, 1 H), 6.31 (d, J=5.5 Hz, 1 H), 6.76 (d, J=11.1 Hz, 1 H), 6.98 (d, J=8.5 Hz, 1 H), 7.23 (d, J=8.0 Hz, 1 H), 7.30 (s, 1 H), 7.47-7.56 (m, 2 H), 7.80-7.91 (m, 3 H), 8.17 (d, J=5.5 Hz, 1 H), 8.25 (s, 1 H).
Reaction SMILES: [Cl:1][CH2:2][CH2:3][N:4]=[C:5]=[O:6].[CH:7]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH:10]=[CH:9][C:8]=1[NH2:17].CO>C1(C)C=CC=CC=1.C(Cl)(Cl)Cl>[Cl:1][CH2:2][CH2:3][NH:4][C:5]([NH:17][C:8]1[CH:9]=[CH:10][C:11]2[C:16](=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH:7]=1)=[O:6]
Reactant: O=C=NCCCl
Reactant: Nc1ccc2ccccc2c1
Solvent: ClC(Cl)Cl
Solvent: Cc1ccccc1
Solvent: CO
Product: O=C(NCCCl)Nc1ccc2ccccc2c1
Temperature: 25 °C
Yield: 83.2 %

Procedure:
1-Chloro-2-isocyanato-ethane (0.81 mL, 9.42 mmol) was added dropwise to a stirred solution of naphthalen-2-ylamine (900 mg, 6.28 mmol) in toluene (50 mL) over a period of 30 minutes at 0° C. The reaction temperature was maintained at room temperature for 5 hours. The reaction was monitored by TLC (5% MeOH in chloroform). The reaction mixture was filtered, washed with toluene and dried under reduced pressure to afford 1.3 g (83% yield) of 1-(2-chloro-ethyl)-3-naphthalen-2-yl-urea.
Reaction SMILES: [CH2:1]([NH2:13])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12].[CH:14](=O)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.C(O)(=O)C>C(O)C>[CH:14](=[N:13][CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1
Reactant: O=Cc1ccccc1
Reactant: CCCCCCCCCCCCN
Solvent: CC(=O)O
Solvent: CCO
Product: CCCCCCCCCCCCN=Cc1ccccc1

Procedure:
18.5 g (0.1 mol.) of n-dodecylamine, 10.6 g (0.1 mol.) of benzaldehyde and a catalytic amount of acetic acid were reacted in anhydrous ethanol at 60°~70° C. for 4 hours. After distilling ethanol off, the residue was further distilled under reduced pressure to obtain N-benzylidene-n-dodecylamine (II), (b.p. 160°~163° C./0.6 mmHg) as a transparent oil which includes low melting solids.
Reaction SMILES: Cl[C:2]1[N:20]=[C:5]2[C:6]([C:10]3[CH:15]=[CH:14][C:13]([P:16]([CH3:19])([CH3:18])=[O:17])=[CH:12][CH:11]=3)=[CH:7][CH:8]=[CH:9][N:4]2[N:3]=1.[NH2:21][C:22]1[CH:23]=[C:24]([N:28]2[CH2:33][CH2:32][N:31]([CH2:34][CH3:35])[CH2:30][C:29]2=[O:36])[CH:25]=[CH:26][CH:27]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)CCCCC1>>[CH3:18][P:16]([CH3:19])([C:13]1[CH:14]=[CH:15][C:10]([C:6]2[C:5]3[N:4]([N:3]=[C:2]([NH:21][C:22]4[CH:23]=[C:24]([N:28]5[CH2:33][CH2:32][N:31]([CH2:34][CH3:35])[CH2:30][C:29]5=[O:36])[CH:25]=[CH:26][CH:27]=4)[N:20]=3)[CH:9]=[CH:8][CH:7]=2)=[CH:11][CH:12]=1)=[O:17]
Reactant: CP(C)(=O)c1ccc(-c2cccn3nc(Cl)nc23)cc1
Reactant: CCN1CCN(c2cccc(N)c2)C(=O)C1
Agent: c1ccc(P(C2CCCCC2)C2CCCCC2)c(-c2ccccc2P(C2CCCCC2)C2CCCCC2)c1
Product: CCN1CCN(c2cccc(Nc3nc4c(-c5ccc(P(C)(C)=O)cc5)cccn4n3)c2)C(=O)C1

Procedure:
1-(3-{8-[4-(Dimethyl-phosphinoyl)-phenyl]-[1,2,4]triazolo[1,5-a]pyridin-2-ylamino}-phenyl)-4-ethyl-piperazin-2-one was prepared from 2-chloro-8-[4-(dimethyl-phosphinoyl)-phenyl]-[1,2,4]triazolo[1,5-a]pyridine (100.0 mg, 0.3271 mmol) and 1-(3-amino-phenyl)-4-ethyl-piperazin-2-one (79.0 mg, 0.360 mmol) with 2,2′-bis-dicyclohexylphosphanyl-biphenyl (28.0 mg, 0.0512 mmol) as the ligand in a manner analogous to Example 2d. MP=205-207° C. 1H NMR (400 MHz, CDCl3, δ, ppm): 8.48 (d, J=6.6 Hz, 1H), 8.13 (d, J=7.9 Hz, 2H), 7.92-7.85 (m, 2H), 7.68 (s, 1H), 7.63 (d, J=7.2 Hz, 1H), 7.44 (d, J=8.0 Hz, 1H), 7.37 (t, J=8.2 Hz, 1H), 7.04-6.97 (m, 2H), 6.93 (d, J=7.5 Hz, 1H), 3.80-3.75 (m, 2H), 3.35 (s, 2H), 2.88-2.83 (m, 2H), 2.57 (q, J=7.0 Hz, 2H), 1.80 (s, 3H), 1.77 (s, 3H), 1.18 (t, J=7.0 Hz, 3H). MS=489 (MH)+.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([OH:29])[CH2:9][CH2:10][N:11]2[CH2:16][CH2:15][CH:14]([C:17]3[CH:18]=[C:19]([NH:23][C:24](=[O:28])[CH:25]([CH3:27])[CH3:26])[CH:20]=[CH:21][CH:22]=3)[CH2:13][CH2:12]2)=[CH:4][CH:3]=1.[Br:30][C:31]1[CH:32]=[C:33](O)[CH:34]=[CH:35][CH:36]=1>>[Br:30][C:31]1[CH:36]=[C:35]([CH:34]=[CH:33][CH:32]=1)[O:29][CH:8]([C:5]1[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=1)[CH2:9][CH2:10][N:11]1[CH2:16][CH2:15][CH:14]([C:17]2[CH:18]=[C:19]([NH:23][C:24](=[O:28])[CH:25]([CH3:26])[CH3:27])[CH:20]=[CH:21][CH:22]=2)[CH2:13][CH2:12]1
Reactant: Oc1cccc(Br)c1
Reactant: CC(C)C(=O)Nc1cccc(C2CCN(CCC(O)c3ccc(F)cc3)CC2)c1
Product: CC(C)C(=O)Nc1cccc(C2CCN(CCC(Oc3cccc(Br)c3)c3ccc(F)cc3)CC2)c1

Procedure:
Prepared by Procedure A and Scheme AN using N-(3-{1-[3-(4-fluorophenyl)-3-hydroxypropyl]-4-piperidinyl}phenyl)-2-methylpropanamide and 3-bromophenol: ESMS m/e: 552.7 (M+H)+.
Reaction SMILES: [CH:1]([C:3]1[CH:4]=[CH:5][C:6]([NH:10][C:11](=[O:16])[C:12]([CH3:15])([CH3:14])[CH3:13])=[N:7][C:8]=1[CH3:9])=[O:2].[BH4-].[Na+]>>[OH:2][CH2:1][C:3]1[CH:4]=[CH:5][C:6]([NH:10][C:11](=[O:16])[C:12]([CH3:14])([CH3:13])[CH3:15])=[N:7][C:8]=1[CH3:9]
Reactant: Cc1nc(NC(=O)C(C)(C)C)ccc1C=O
Agent: [BH4-]
Agent: [Na+]
Product: Cc1nc(NC(=O)C(C)(C)C)ccc1CO

Procedure:
This material was prepared in analogy to example 107 step B] from N-(5-formyl-6-methyl-pyridin-2-yl)-2,2-dimethyl-propionamide (5.9 g) and sodium borohydride (1.037 g) as a light yellow solid (1.41 g). MS (ESI): 223.2 (MH+).
Reaction SMILES: [I:1]I.[CH3:3][C@@H:4]1[C@@:21]2([CH3:22])[C:8]([CH2:9][CH2:10][C@@H:11]3[C@@H:20]2[CH2:19][CH2:18][C@@:16]2([CH3:17])[C@H:12]3[CH2:13][CH2:14][C:15]2=[O:23])=[CH:7][C:6](=[O:24])[CH2:5]1>C(O)(=O)C>[I:1][CH:5]1[C@H:4]([CH3:3])[C@@:21]2([CH3:22])[C:8]([CH2:9][CH2:10][C@@H:11]3[C@@H:20]2[CH2:19][CH2:18][C@@:16]2([CH3:17])[C@H:12]3[CH2:13][CH2:14][C:15]2=[O:23])=[CH:7][C:6]1=[O:24]
Reactant: C[C@H]1CC(=O)C=C2CC[C@@H]3[C@H](CC[C@]4(C)C(=O)CC[C@@H]34)[C@]21C
Reactant: II
Solvent: CC(=O)O
Product: C[C@H]1C(I)C(=O)C=C2CC[C@@H]3[C@H](CC[C@]4(C)C(=O)CC[C@@H]34)[C@]21C
Temperature: 25 °C
Yield: 106.6 %

Procedure:
10.3 g (40 mmol) of iodine is added to 10 g (33 mmol) of 1α-methyl-androst-4-ene-3,17-dione and 7.33 g (40 mmol) of CuO in 300 ml of glacial acetic acid with stirring at room temperature. It is stirred under nitrogen atmosphere for 24 hours at 60° C. Under reduced pressure, acetic acid is distilled off. The residue is added in 600 ml of water, the product is extracted 3 times with 200 ml of ethyl acetate each, the combined ethyl acetate phases are washed neutral with sodium thiosulfate solution, then with saturated sodium carbonate solution and dried on sodium sulfate. After concentration by evaporation of the solution and drying of the substance at 0.8 torr, 15.0 g (106% of theory) of 2-iodo-1α-methyl-androst-4-ene-3,17-dione is obtained as crude product.