Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[CH:4][CH:3]=1.[Mg].II.[Si:15](Cl)([Cl:18])([Cl:17])[Cl:16]>C1COCC1>[C:2]1([Si:15]([Cl:18])([Cl:17])[Cl:16])[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[CH:4][CH:3]=1
Reactant: Cl[Si](Cl)(Cl)Cl
Reactant: Brc1cccc2ccccc12
Agent: II
Agent: [Mg]
Solvent: C1CCOC1
Product: Cl[Si](Cl)(Cl)c1cccc2ccccc12
Temperature: 25 °C
Reaction time: 8 h
Yield: 67.3 %

Procedure:
Under a dry nitrogen atmosphere, a solution of 1-bromonaphthalene (27.7 g, 0.134 mol) in THF (175 mL) was added slowly to a suspension of magnesium turnings (3.9 g, 0.16 mol) in THF (15 mL) that had previously been activated with an iodine crystal. After cooling to room temperature, this Grignard reagent was added via canula to a THF (70 mL) solution of SiCl4 (25.1 g, 0.148 mol) and stirred overnight. The mixture was evaporated to dryness, extracted with hexane and filtered to remove Mg halide. The product was distilled at 120° C. under dynamic vacuum to give a 67% yield (23.6 g, 0.0902 mol) of product. 1H NMR (CDCl3, ppm) 8.46 (dd, 1H), 8.21 (dd, J=6.8 Hz, J=1.2 Hz, 1H), 8.09 (d, J=8.4 Hz, 1H), 7.96 (d, J=7.6 Hz, 1H), 7.69 (t, 1H), 7.62 (t, 1H), 7.57 (t, 1H). 13C{1H}NMR (CDCl3, ppm) 135.51 (CH), 134.42 (C), 134.07 (CH), 133.58 (C), 129.37 (CH), 127.91 (C), 127.45 (CH), 127.16 (CH), 126.56 (CH), and 124.65 (CH). 29Si{1H} (CDCl3, ppm) −0.17 (s).
Reaction SMILES: C[O:2][C:3](=[O:12])[CH2:4][CH2:5][N:6]1[CH:10]=[C:9](I)[CH:8]=[N:7]1.[S:13]1[C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=2[N:15]=[C:14]1[C:22]1[C:23]([NH2:37])=[N:24][CH:25]=[C:26](B2OC(C)(C)C(C)(C)O2)[CH:27]=1.[F-].[K+]>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.O1CCOCC1.O>[NH2:37][C:23]1[N:24]=[CH:25][C:26]([C:9]2[CH:8]=[N:7][N:6]([CH2:5][CH2:4][C:3]([OH:2])=[O:12])[CH:10]=2)=[CH:27][C:22]=1[C:14]1[S:13][C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=2[N:15]=1
Reactant: CC1(C)OB(c2cnc(N)c(-c3nc4ccccc4s3)c2)OC1(C)C
Reactant: COC(=O)CCn1cc(I)cn1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [F-]
Agent: [K+]
Solvent: C1COCCO1
Solvent: O
Product: Nc1ncc(-c2cnn(CCC(=O)O)c2)cc1-c1nc2ccccc2s1
Temperature: 85 °C

Procedure:
A mixture of 3-(4-iodopyrazol-1-yl)-propionic acid methyl ester (174 mg, 0.623 mmol), 3-benzothiazol-2-yl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-pyridin-2-ylamine (200.0 mg, 0.5662 mmol), Pd(PPh3)4 (50 mg, 0.04 mmol), potassium fluoride (98.7 mg, 1.70 mmol), and 4:1 dioxane:water (4:1, 1,4-dioxane:H2O, 8 mL) was heated in the microwave reactor at 85° C. for 30 min. The solution was concentrated in vacuo, and dry-loaded onto silica gel for column chromatography. The material was eluted with 2% MeOH/DCM. The fractions containing the product were concentrated in vacuo. The material was dissolved in conc. HCl (4 mL) and heated to 60° C. for 30 min in a sealed tube. The solvent was removed using the corrosive pump to afford the title compound as an orange solid. MS (ES+): m/z=366.14 (100) [MH+]. HPLC: tR=2.59 min (ZQ2, polar—5 min).
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([SH:8])=[CH:4][CH:3]=1.Br[CH2:10][C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12]>>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([S:8][CH2:10][C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])=[CH:4][CH:3]=1
Reactant: CC(C)(C)OC(=O)CBr
Reactant: Sc1ccc(Br)cc1
Product: CC(C)(C)OC(=O)CSc1ccc(Br)cc1

Procedure:
The subject compound was prepared starting from 4-bromobenzenethiol and t-butyl bromoacetate in the same manner as Reference example 6-1.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:13]3[N:14]=[C:15]([S:26][CH3:27])[C:16]([N:17]([CH2:22][CH:23]4[CH2:25][CH2:24]4)[CH2:18][CH:19]4[CH2:21][CH2:20]4)=[C:12]3[CH:11]=[CH:10][CH:9]=2)=[C:4]([O:28][CH3:29])[CH:3]=1.C(OCC)(=O)C.[CH3:36][N:37](C)C=O>[C-]#N.[Zn+2].[C-]#N>[CH:19]1([CH2:18][N:17]([CH2:22][CH:23]2[CH2:25][CH2:24]2)[C:16]2[C:15]([S:26][CH3:27])=[N:14][N:13]3[C:8]([C:5]4[CH:6]=[CH:7][C:2]([C:36]#[N:37])=[CH:3][C:4]=4[O:28][CH3:29])=[CH:9][CH:10]=[CH:11][C:12]=23)[CH2:21][CH2:20]1
Reactant: CN(C)C=O
Reactant: COc1cc(Br)ccc1-c1cccc2c(N(CC3CC3)CC3CC3)c(SC)nn12
Agent: [C-]#N
Agent: [Zn+2]
Solvent: CCOC(C)=O
Product: COc1cc(C#N)ccc1-c1cccc2c(N(CC3CC3)CC3CC3)c(SC)nn12
Temperature: 95 °C
Reaction time: 12 h

Procedure:
After dissolving N-[7-(4-bromo-2-methoxyphenyl)-2-(methylsulfanyl)pyrazolo[1,5-a]pyridin-3-yl]-N,N-dicyclopropylmethylamine (60 mg) in N,N-dimethylformamide (0.26 mL), zinc cyanide (31 mg) and tetrakis (triphenylphosphine)palladium (0) complex (23 mg) were added, the mixture was heated and stirred at 95° C. for 12 hours and then cooled to room temperature, and ethyl acetate was added. After filtering out the precipitated insoluble portion, extraction was performed with ethyl acetate. The obtained organic layer was washed with water and dried over magnesium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (ethyl acetate:n-hexane=1:8) to obtain the title compound (32 mg) as a yellow oil.
Reaction SMILES: [C:1]([C:3]1[CH:4]=[C:5]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][CH:16]=[C:17]([NH:20][C:21](=[O:29])[CH:22]=[C:23]4[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]4)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:6]=[CH:7][CH:8]=1)#[CH:2].CI.[C:32](=O)([O-])[O-].[K+].[K+]>C(#N)C>[C:1]([C:3]1[CH:4]=[C:5]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][CH:16]=[C:17]([NH:20][C:21](=[O:29])[CH:22]=[C:23]4[CH2:28][CH2:27][N:26]([CH3:32])[CH2:25][CH2:24]4)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:6]=[CH:7][CH:8]=1)#[CH:2]
Reactant: O=C([O-])[O-]
Reactant: C#Cc1cccc(Nc2ncnc3ccc(NC(=O)C=C4CCNCC4)cc23)c1
Agent: [K+]
Solvent: CI
Solvent: CC#N
Product: C#Cc1cccc(Nc2ncnc3ccc(NC(=O)C=C4CCN(C)CC4)cc23)c1
Temperature: 25 °C
Reaction time: 24 h

Procedure:
N-(4-(3-ethynylphenylamino)quinazolin-6-yl)-2-(piperidin-4-ylidene)acetamide (20 mg, 0.046 mmol), methyl iodide (8.0 mg, 0.056 mmol), anhydrous potassium carbonate (17 mg), and acetonitrile (5 mL) were placed in a one-neck flask (50 mL). The reaction mixture was stirred at room temperature for 24 hours. After reaction completion, the solution was filtered, and evaporated in vacuo to give a solid. The solid was purified by TLC (silica gel plate, thickness 5 mm, chloroform:methanol=95:5). MS: 398 (M+1).
Reaction SMILES: [CH3:1][N:2]([CH3:20])[C:3]([C:5]1[N:14]([CH:15]2[CH2:19][CH2:18][CH2:17][CH2:16]2)[C:8]2[N:9]=[C:10](Cl)[N:11]=[CH:12][C:7]=2[CH:6]=1)=[O:4].[NH2:21][C:22]1[N:27]=[CH:26][C:25]([N:28]2[CH2:33][CH2:32][NH:31][C:30](=[O:34])[CH2:29]2)=[CH:24][CH:23]=1>>[CH3:1][N:2]([CH3:20])[C:3]([C:5]1[N:14]([CH:15]2[CH2:19][CH2:18][CH2:17][CH2:16]2)[C:8]2[N:9]=[C:10]([NH:21][C:22]3[CH:23]=[CH:24][C:25]([N:28]4[CH2:33][CH2:32][NH:31][C:30](=[O:34])[CH2:29]4)=[CH:26][N:27]=3)[N:11]=[CH:12][C:7]=2[CH:6]=1)=[O:4]
Reactant: Nc1ccc(N2CCNC(=O)C2)cn1
Reactant: CN(C)C(=O)c1cc2cnc(Cl)nc2n1C1CCCC1
Product: CN(C)C(=O)c1cc2cnc(Nc3ccc(N4CCNC(=O)C4)cn3)nc2n1C1CCCC1
Yield: 23 %

Procedure:
Following Buchwald Method B, 2-chloro-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid dimethylamide (100 mg, 0.34 mmol) and 4-(6-amino-pyridin-3-yl)-piperazin-2-one (111 mg, 0.578 mmol) gave 7-cyclopentyl-2-[5-(3-oxo-piperazin-1-yl)-pyridin-2-ylamino]-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid dimethylamide (35 mg, 35%). MS (ESI) m/z 449.2 (M+H)+
Reaction SMILES: [F:1][C:2]([F:32])([F:31])[C:3]1[CH:30]=[CH:29][CH:28]=[CH:27][C:4]=1[O:5][CH:6]1[CH2:11][CH2:10][N:9]([C:12]2[S:13][C:14]([C:17]3[S:18][CH:19]=[C:20]([CH2:22][C:23]([O:25]C)=[O:24])[N:21]=3)=[CH:15][N:16]=2)[CH2:8][CH2:7]1.[OH-].[Na+]>C1COCC1.CO>[F:32][C:2]([F:1])([F:31])[C:3]1[CH:30]=[CH:29][CH:28]=[CH:27][C:4]=1[O:5][CH:6]1[CH2:11][CH2:10][N:9]([C:12]2[S:13][C:14]([C:17]3[S:18][CH:19]=[C:20]([CH2:22][C:23]([OH:25])=[O:24])[N:21]=3)=[CH:15][N:16]=2)[CH2:8][CH2:7]1
Reactant: COC(=O)Cc1csc(-c2cnc(N3CCC(Oc4ccccc4C(F)(F)F)CC3)s2)n1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: C1CCOC1
Product: O=C(O)Cc1csc(-c2cnc(N3CCC(Oc4ccccc4C(F)(F)F)CC3)s2)n1

Procedure:
A mixture of methyl (2′-{4-[2-(trifluoromethyl)phenoxy]piperidin-1-yl}-2,5′-bi-1,3-thiazol-4-yl)acetate (220 mg, 0.44 mmol) in THF/MeOH (4:1) (v/v) (5 mL) was treated with 1 N NaOH (1 mL, 1 mmol) and heated at reflux temperature for 2 h. Volatile materials were removed in vacuo. The residue was diluted with water, acidified with 1 N HCl and extracted with EtOAc. The EtOAc extract was washed twice with water, dried (Na2SO4) and concentrated to give the title compound as a yellow foam.
Reaction SMILES: [C:1]1([S:7][C:8]2[S:9][CH:10]=[CH:11][C:12]=2[CH2:13][C:14]([OH:16])=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH2:17]([O:21][C:22](=[O:26])[C@H:23]([CH3:25])[NH2:24])[CH:18]([CH3:20])[CH3:19]>>[CH2:17]([O:21][C:22](=[O:26])[C@H:23]([CH3:25])[NH:24][C:14](=[O:16])[CH2:13][C:12]1[CH:11]=[CH:10][S:9][C:8]=1[S:7][C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1)[CH:18]([CH3:20])[CH3:19]
Reactant: CC(C)COC(=O)[C@H](C)N
Reactant: O=C(O)Cc1ccsc1Sc1ccccc1
Product: CC(C)COC(=O)[C@H](C)NC(=O)Cc1ccsc1Sc1ccccc1

Procedure:
Following General Procedure I′ above, and using (2-phenylthiothienyl)acetic acid and alanine iso-butyl ester (prepared following General Procedure J′ above), the title compound was prepared. The reaction was monitored by tlc on silica gel and purification was by filtration as described in the general procedure.
Reaction SMILES: [CH3:1][C@H:2]([C:11]([O:13][C:14]1[CH:19]=[CH:18][C:17]([O:20][C:21]([C:23]2[CH:28]=[CH:27][C:26]([O:29]CC3C=CC=CC=3)=[CH:25][CH:24]=2)=[O:22])=[CH:16][CH:15]=1)=[O:12])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10]>[Pd].C(OCC)(=O)C>[CH3:1][C@H:2]([C:11]([O:13][C:14]1[CH:15]=[CH:16][C:17]([O:20][C:21]([C:23]2[CH:24]=[CH:25][C:26]([OH:29])=[CH:27][CH:28]=2)=[O:22])=[CH:18][CH:19]=1)=[O:12])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10]
Reactant: CCCCCCCC[C@H](C)C(=O)Oc1ccc(OC(=O)c2ccc(OCc3ccccc3)cc2)cc1
Agent: [Pd]
Solvent: CCOC(C)=O
Product: CCCCCCCC[C@H](C)C(=O)Oc1ccc(OC(=O)c2ccc(O)cc2)cc1
Reaction time: 6 h
Yield: 85.8 %

Procedure:
{circle around (4)}: A mixture comprising 2.0 g of (S)-4-[4′-(1″-methylnonylcarbonyloxy)phenyloxycarbonyl]-1-benzyloxybenzene, 0.2 g of palladium/carbon and 10 g of ethyl acetate was stirred for 6 hours under hydrogen atmosphere. Then, palladium/carbon was filtered off, followed by distilling off ethyl acetate from the filtrate. The resultant residue was recrystallized from hexane, whereby 1.4 g of (S)-4-[4′-(1″-methylnonylcarbonyloxy)phenyloxycarbonyl]phenol was obtained in the form of a colorless crystal.
Reaction SMILES: C(O)=O.C(N(CC)CC)C.[CH:11]([CH:13]1[CH2:18][O:17][CH2:16][CH2:15][N:14]1[C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])=O.[CH3:26][C:27]1(C)[O:34]C(=O)CC(=O)[O:28]1>[OH-].[Na+]>[C:22]([O:21][C:19]([N:14]1[CH2:15][CH2:16][O:17][CH2:18][CH:13]1[CH2:11][CH2:26][C:27]([OH:34])=[O:28])=[O:20])([CH3:25])([CH3:24])[CH3:23]
Reactant: CC(C)(C)OC(=O)N1CCOCC1C=O
Reactant: CC1(C)OC(=O)CC(=O)O1
Agent: [Na+]
Agent: [OH-]
Solvent: O=CO
Solvent: CCN(CC)CC
Product: CC(C)(C)OC(=O)N1CCOCC1CCC(=O)O
Temperature: 100 °C
Reaction time: 0.08 h
Yield: 40.3 %

Procedure:
A mixture of formic acid (2.26 mL, 58.9 mmol) and triethylamine (3.36 mL, 24.11 mmol) was stirred for 5 minutes in an ice bath. To the mixture were added tert-butyl 3-formylmorpholine-4-carboxylate (0.47 g, 2.2 mmol) and Meldrum's acid (0.32 g, 2.2 mmol) in turn at 0° C. The reaction mixture was heated at 100° C. for 5 hours, and cooled down in an ice bath. To the resulting mixture was added aqueous NaOH solution (2 mol/L, 40 mL). The aqueous layer was extracted with EtOAc (50 mL×3) and the organic layer was discarded. To the aqueous layer was added EtOAc (80 mL), and the mixture was adjusted to pH 4-5 with HCl (1 mol/L) under stirring. The aqueous layer was extracted with EtOAc (80 mL). The organic layer was dried over anhydrous Na2SO4, then filtered and the filtrate was concentrated in vacuo to give the title compound as a white solid (0.23 g, 40%). The compound was characterized by the following spectroscopic data:
Reaction SMILES: C([O:4][CH2:5][CH2:6][CH2:7][CH2:8][C:9]#[C:10][CH2:11][O:12][C:13]1[CH:18]=[CH:17][C:16]([S:19]([N:22]2[CH2:27][CH2:26][S:25][C:24]([CH3:29])([CH3:28])[C@@H:23]2[C:30]([NH:32][OH:33])=[O:31])(=[O:21])=[O:20])=[CH:15][CH:14]=1)(=O)C.[OH-].[NH4+]>CO>[OH:33][NH:32][C:30]([C@H:23]1[C:24]([CH3:28])([CH3:29])[S:25][CH2:26][CH2:27][N:22]1[S:19]([C:16]1[CH:17]=[CH:18][C:13]([O:12][CH2:11][C:10]#[C:9][CH2:8][CH2:7][CH2:6][CH2:5][OH:4])=[CH:14][CH:15]=1)(=[O:21])=[O:20])=[O:31]
Reactant: CC(=O)OCCCCC#CCOc1ccc(S(=O)(=O)N2CCSC(C)(C)[C@@H]2C(=O)NO)cc1
Agent: [NH4+]
Agent: [OH-]
Solvent: CO
Product: CC1(C)SCCN(S(=O)(=O)c2ccc(OCC#CCCCCO)cc2)[C@H]1C(=O)NO
Yield: 64.6 %

Procedure:
A mixture of 0.152 g (0.305 mmol) of 7-[4-({(3S)-3-[(hydroxyamino)-carbonyl]-2,2-dimethylthiomorpholinyl}sulfonyl)phenoxy]-5-heptynyl acetate, 3 mL of aqueous ammonium hydroxide and 3 mL of methanol was stirred at room temperature for 18h and concentrated in vacuo. The residue was chromatographed on silica gel eluting with 1.5% methanol/dichloromethane to provide 0.09 g (65%) of (3S)-N-hydroxy4-((4-[(7-hydroxy-2-heptynyl)oxy]phenyl}sulfonyl)-2,2-dimethyl-3-thiomorpholinecarboxamide as a white solid. Electrospray Mass Spec: 457.0(M+H)+
Reaction SMILES: [N+:1]([C:4]1[C:8]([C:9]2[CH:14]=[C:13]([C:15]([F:18])([F:17])[F:16])[CH:12]=[CH:11][C:10]=2[OH:19])=[CH:7][N:6]([CH:20]2[CH2:25][CH2:24][CH2:23][CH2:22][O:21]2)[N:5]=1)([O-:3])=[O:2].C(=O)([O-])[O-].[K+].[K+].[Cl:32][C:33]1[C:34](F)=[CH:35][C:36]([F:55])=[C:37]([S:39]([N:42]([C:50]2[N:51]=[CH:52][S:53][CH:54]=2)[C:43](=[O:49])[O:44][C:45]([CH3:48])([CH3:47])[CH3:46])(=[O:41])=[O:40])[CH:38]=1>CS(C)=O.C(OCC)(=O)C.ClC1C(F)=CC(F)=C(S(N(C2N=CSC=2)C(=O)OC(C)(C)C)(=O)=O)C=1>[Cl:32][C:33]1[C:34]([O:19][C:10]2[CH:11]=[CH:12][C:13]([C:15]([F:17])([F:18])[F:16])=[CH:14][C:9]=2[C:8]2[C:4]([N+:1]([O-:3])=[O:2])=[N:5][N:6]([CH:20]3[CH2:25][CH2:24][CH2:23][CH2:22][O:21]3)[CH:7]=2)=[CH:35][C:36]([F:55])=[C:37]([S:39]([N:42]([C:50]2[N:51]=[CH:52][S:53][CH:54]=2)[C:43](=[O:49])[O:44][C:45]([CH3:48])([CH3:47])[CH3:46])(=[O:41])=[O:40])[CH:38]=1
Reactant: O=[N+]([O-])c1nn(C2CCCCO2)cc1-c1cc(C(F)(F)F)ccc1O
Reactant: CC(C)(C)OC(=O)N(c1cscn1)S(=O)(=O)c1cc(Cl)c(F)cc1F
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CS(C)=O
Solvent: CCOC(C)=O
Product: CC(C)(C)OC(=O)N(c1cscn1)S(=O)(=O)c1cc(Cl)c(Oc2ccc(C(F)(F)F)cc2-c2cn(C3CCCCO3)nc2[N+](=O)[O-])cc1F
Temperature: 45 °C
Reaction time: 0.17 h
Yield: 66.5 %

Procedure:
To a solution of 2-[3-nitro-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl]-4-(trifluoromethyl)phenol (Preparation 868, 28.73 g, 80.41 mmol) in dimethyl sulfoxide (175 mL) was added potassium carbonate (22.3 g, 161 mmol). After stirring for 10 minutes, tert-butyl [(5-chloro-2,4-difluorophenyl)sulfonyl]1,3-thiazol-4-ylcarbamate (Preparation 453, 33.02 g, 80.37 mmol) was added. After stirring for 14 hours at room temperature, additional potassium carbonate (4.7 g, 34 mmol) and tert-butyl [(5-chloro-2,4-difluorophenyl)sulfonyl]1,3-thiazol-4-ylcarbamate (1.25 g, 3.0 mmol) were added and the reaction mixture heated at 45° C. for 7 hours. The mixture was allowed to cool, diluted with ethyl acetate, and washed with water and brine. The organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated. Purification by manual flash column chromatography using 25% ethyl acetate/hexanes and an 8×46 cm column provided product as a yellow oil (40 g, 70%).
Reaction SMILES: C([NH:9][C:10]([NH:12][CH:13]1[CH2:18][CH2:17][N:16]([CH2:19][C:20]2[CH:29]=[CH:28][C:27]3[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=3)[CH:21]=2)[CH2:15][CH2:14]1)=[O:11])(=O)C1C=CC=CC=1>[OH-].[Na+]>[CH:21]1[C:22]2[C:27](=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH:28]=[CH:29][C:20]=1[CH2:19][N:16]1[CH2:17][CH2:18][CH:13]([NH:12][C:10]([NH2:9])=[O:11])[CH2:14][CH2:15]1
Reactant: O=C(NC(=O)c1ccccc1)NC1CCN(Cc2ccc3ccccc3c2)CC1
Agent: [Na+]
Agent: [OH-]
Product: NC(=O)NC1CCN(Cc2ccc3ccccc3c2)CC1

Procedure:
1-Benzoyl-3-[1-(naphth-2-ylmethyl)piperid-4-yl]urea (prepared acccording to Example 1) is hydrolysed by refluxing in 2N sodium hydroxide to give [1-(naphth-2-ylmethyl)piperid-4-yl]urea(m.p. 183°-5° C.). The product is acylated by reaction with 4-methoxybenzoyl chloride to give the title compound, m.p. of HCL, quarterhydrate=193°-193.5° C.).
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[S:10](Cl)(=[O:12])=[O:11])([O-:3])=[O:2].[CH:14]1([NH:20][C:21]([CH:23]2[CH2:28][CH2:27][CH2:26][NH:25][CH2:24]2)=[O:22])[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]1.C(N(CC)CC)C>C(#N)C>[CH:14]1([NH:20][C:21]([CH:23]2[CH2:28][CH2:27][CH2:26][N:25]([S:10]([C:5]3[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=3[N+:1]([O-:3])=[O:2])(=[O:12])=[O:11])[CH2:24]2)=[O:22])[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19]1
Reactant: O=[N+]([O-])c1ccccc1S(=O)(=O)Cl
Reactant: O=C(NC1CCCCC1)C1CCCNC1
Solvent: CCN(CC)CC
Solvent: CC#N
Product: O=C(NC1CCCCC1)C1CCCN(S(=O)(=O)c2ccccc2[N+](=O)[O-])C1
Temperature: 25 °C
Reaction time: 2 h
Yield: 60.1 %

Procedure:
To a solution of 2-nitrobenzene-1-sulfonyl chloride (12.3 mg) and N-cyclohexylpiperidine-3-carboxamide (TFA salt, 18 mg) from Step 2 in 0.2 mL acetonitrile was added triethylamine (19.3 μL). The reaction mixture was stirred at RT for 2 hours and directly purified by HPLC to give 13.2 mg of desired product. LCMS: m/z 396.1 (M+H)+; 813.3 (2M+Na)+.
Reaction SMILES: [CH3:1][CH:2]([C@H:4]1[CH2:8][O:7][C:6](=[O:9])[NH:5]1)[CH3:3].[Li]CCCC.CCCCCC.[C:21](Cl)(=[O:24])[CH2:22][CH3:23]>C1COCC1>[O:24]=[C:21]([N:5]1[C@@H:4]([CH:2]([CH3:3])[CH3:1])[CH2:8][O:7][C:6]1=[O:9])[CH2:22][CH3:23]
Reactant: CC(C)[C@H]1COC(=O)N1
Reactant: CCC(=O)Cl
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CCCCCC
Product: CCC(=O)N1C(=O)OC[C@@H]1C(C)C
Temperature: -78 °C
Reaction time: 0.25 h
Yield: 79.8 %

Procedure:
To a cooled solution (-78° C.) of 1.5910 g (12.316 mmole of (+)-(4S)-3-(1-oxopropyl)-4-(1-methylethyl)-2-oxoazolidinone (A) in 20 ml of THF under N2 atmosphere is added 5.80 ml of 2.32M n-BuLi in hexane (13.55 mmole, 1.1 equiv.) to form the conjugate base. The milky slurry is stirred for 1 hour before 1.11 ml (1.1852 g, 12.81 mmoles, 1.04 equiv., mwt 92.53, bp 77°-9° C., d 1.065) of propionyl chloride is added in one portion. The slurry dissolves instantly to a clear orange solution. After stirring an additional 15 min. at -78° C., the reaction is quenched with 20 ml sat. NH4Cl, and the THF is removed in vacuo at RT (room temp). The resultant concentrate is taken up in ether and extracted successively with aq. NaHCO3, water, brine and dried over anh. Na2SO4. Evaporation of the solvent followed by flash chromatography affords 1.82 g (80%) of purified product B as a viscous yellow oil. Proton NMR (200 MHz) in CDCl3 shows: ##STR58## 4.41 (d of t, 1H, J=7.6 Hz, J=3.6 Hz, C3 -H); 4.22 (m, 2H, 2J=5.4 Hz, C4 -H); 2.92 (q of d, 2H, J=7.7 Hz, J=4.0 Hz, C9 -H); 2.35 (m, 1H, J=7.0 Hz, J=3.9 Hz, C2 -H); 1.14 (t, 3H, J=7.7 Hz, C10 -H); 0.89, 0.85 (d, 6H, J=7.0 Hz, C1 -H).
Reaction SMILES: [CH3:1][C:2]1[N:3]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[C:4](=[O:15])[C:5]2[C:10]([C:11]=1[C:12](Cl)=[O:13])=[CH:9][CH:8]=[CH:7][CH:6]=2.Cl.[C:23]1([N:29]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[NH2:30])[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1>ClCCCl>[C:23]1([N:29]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[NH:30][C:12]([C:11]2[C:10]3[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=3)[C:4](=[O:15])[N:3]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[C:2]=2[CH3:1])=[O:13])[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1
Reactant: NN(c1ccccc1)c1ccccc1
Reactant: Cc1c(C(=O)Cl)c2ccccc2c(=O)n1-c1ccccc1
Agent: Cl
Solvent: ClCCCl
Product: Cc1c(C(=O)NN(c2ccccc2)c2ccccc2)c2ccccc2c(=O)n1-c1ccccc1
Temperature: 140 °C

Procedure:
A mixture of 3-methyl-1-oxo-2-phenyl-1,2-dihydro-isoquinoline-4-carbonyl chloride (the synthesis is described above in example 1a) (25 mg, 0.08 mmol) and 1,1-diphenylhydrazine hydrochloride (56 mg, 0.25 mmol) in 1,2-dichloroethane (1 ml) was heated under microwave irradiation for 20 min at 140° C. Volatiles were removed in vacuo and the product was purified by preparative LC-MS to give 14 mg of colorless solid. LC-MS (m/z) 446.7 (MH+); tR=1.58.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([NH:15][C:16]2[C:25]3[C:20](=[CH:21][CH:22]=[C:23](Br)[CH:24]=3)[N:19]=[CH:18][N:17]=2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([Sn](CCCC)(CCCC)[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][N:33]=1)CCC>O1CCOCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([NH:15][C:16]2[C:25]3[C:20](=[CH:21][CH:22]=[C:23]([C:32]4[CH:37]=[CH:36][CH:35]=[CH:34][N:33]=4)[CH:24]=3)[N:19]=[CH:18][N:17]=2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: Brc1ccc2ncnc(Nc3ccc(OCc4ccccc4)cc3)c2c1
Reactant: CCCC[Sn](CCCC)(CCCC)c1ccccn1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: C1COCCO1
Product: c1ccc(COc2ccc(Nc3ncnc4ccc(-c5ccccn5)cc34)cc2)cc1
Yield: 55.5 %

Procedure:
The (4-benzyloxy-phenyl)-(6-bromoquinazolin-4-yl)-amine (200 mg, 0.49 mmol), 2-(tributylstannyl)pyridine (200 mg, 0.53 mmol) and bis(triphenylphosphine)palladium(II) chloride (catalytic) were dissolved in dioxan (3 ml) and heated at reflux under nitrogen for 9 hr. The cooled reaction mixture was absorbed onto silica and purified by flash column chromatography (silica gel, eluting with an ethyl acetate/iso-hexane gradient). The resulting solid was triturated with iso-hexane/ethyl acetate to give the product (110 mg, 56%) as a pale yellow solid; δH [2H6]-DMSO 9.99 (1H, b, NH), 9.18 (1H, s, 5-H), 8.76 (1H, d, pyridine-H), 8.60 (1H, d, 7-H), 8.54 (1H, s, 2-H), 8.23 (1H, d, pyridine-H), 8.00 (1H, t, pyridine-H), 7.87 (1H, d, 8-H), 7.70 (2H, d, 2′-H, 6′-H), 7.53-7.31 (6H, m, 5×Ph-H, pyridine-H), 7.09 (2H, d, 3′-H, 5′-H), 5.14 (2H, s, CH2); m/z 405 (M+1)+.
Reaction SMILES: [N-:1]=[N+:2]=[N-:3].[Na+].CS(O[C@H:10]1[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[C@@H:12]([C:23]([O:25][CH3:26])=[O:24])[CH2:11]1)(=O)=O.O>CN(C=O)C>[N:1]([C@@H:10]1[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:20])([CH3:21])[CH3:22])=[O:17])[C@@H:12]([C:23]([O:25][CH3:26])=[O:24])[CH2:11]1)=[N+:2]=[N-:3]
Reactant: [N-]=[N+]=[N-]
Reactant: COC(=O)[C@H]1C[C@@H](OS(C)(=O)=O)CCN1C(=O)OC(C)(C)C
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: COC(=O)[C@H]1C[C@H](N=[N+]=[N-])CCN1C(=O)OC(C)(C)C
Temperature: 60 °C
Yield: 97.7 %

Procedure:
NaN3 (15.8 g, 243 mmol) was added to a solution of (2R,4S)-1-tert-butyl 2-methyl 4-(methylsulfonyloxy)piperidine-1,2-dicarboxylate (26.7 g, 81 mmol) in dry DMF (100 mL). The mixture was heated at 60° C. for 18 hours. Water (300 mL) was added to the reaction mixture and extracted with ethyl acetate/heptane (2:1) (2×200 mL). The combined organic layer was washed by brine and dried over MgSO4, filtered and concentrated under reduced pressure to give a colorless oil 22.5 g (98%). LC-MS: 285.0 (t=2.5 min).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[C:7]([S:9][CH3:10])[CH:6]=[CH:5][C:4]=1[C:11]1[NH:19][C:18]2[C:13](=[N:14][CH:15]=[N:16][CH:17]=2)[N:12]=1.[OH:20]O>FC(F)(F)C(O)=O.O.C(=O)([O-])[O-].[K+].[K+]>[CH3:1][O:2][C:3]1[CH:8]=[C:7]([S:9]([CH3:10])=[O:20])[CH:6]=[CH:5][C:4]=1[C:11]1[NH:19][C:18]2[C:13](=[N:14][CH:15]=[N:16][CH:17]=2)[N:12]=1
Reactant: COc1cc(SC)ccc1-c1nc2ncncc2[nH]1
Reactant: OO
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: O=C(O)C(F)(F)F
Product: COc1cc(S(C)=O)ccc1-c1nc2ncncc2[nH]1
Temperature: 5 °C
Reaction time: 0.5 h

Procedure:
An amount of 2.27 g of 8-(2-methoxy-4-methylmercaptophenyl)-purine was dissolved in 20 ml of trifluoro acetic acid, and 1.2 ml of 30% hydrogen peroxide were added under cooling to 5° C. After stirring for 3 hours at room temperature and for 0.5 hours at 30° C., the reaction mixture was diluted with water and neutralized with potassium carbonate, and the residue obtained after evaporation was extracted with hot ethanol. The product obtained was purified over silicagel (eluate: methylene chloride/ethanol in a volume ratio of 19:1).