Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][N:2]1[C:10]([NH2:11])=[C:9]2[C:4]([CH2:5][CH2:6][CH2:7][CH2:8]2)=[N:3]1.[C:12]([N:20]=[C:21]=[S:22])(=[O:19])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1>CC(C)=O>[CH3:1][N:2]1[C:10]([NH:11][C:21]([NH:20][C:12](=[O:19])[C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=2)=[S:22])=[C:9]2[C:4]([CH2:5][CH2:6][CH2:7][CH2:8]2)=[N:3]1
Reactant: Cn1nc2c(c1N)CCCC2
Reactant: O=C(N=C=S)c1ccccc1
Solvent: CC(C)=O
Product: Cn1nc2c(c1NC(=S)NC(=O)c1ccccc1)CCCC2
Temperature: 60 °C

Procedure:
To a solution of compound 124 (5.44 g, 33.1 mmol) in 40 mL of acetone at 0° C. was added dropwise benzoyl isothiocynate (5.4 g, 33.1 mmol). The reaction mixture was gradually warmed up and stirred in an oil bath of 60° C. until TLC indicated there was no starting material remained.
Reaction SMILES: F[C:2]1[C:7]([C:8]#[N:9])=[C:6]([F:10])[C:5]([C:11]#[N:12])=[C:4]([F:13])[C:3]=1[F:14].[CH:15]([OH:19])([CH2:17][CH3:18])[CH3:16]>C(#N)C>[F:10][C:6]1[C:5]([C:11]#[N:12])=[C:4]([F:13])[C:3]([F:14])=[C:2]([O:19][CH:15]([CH2:17][CH3:18])[CH3:16])[C:7]=1[C:8]#[N:9]
Reactant: N#Cc1c(F)c(F)c(F)c(C#N)c1F
Reactant: CCC(C)O
Solvent: CC#N
Product: CCC(C)Oc1c(F)c(F)c(C#N)c(F)c1C#N
Temperature: 25 °C
Reaction time: 24 h
Yield: 89 %

Procedure:
A 3.0 g amount of tetrafluoroisophthalonitrile and 1.26 g of 20 ml acetonitrile were dissolved in 20 ml of acetonitrile. A 1.66 g amount of sec-butanol was dropwise added to the mixture and the mixture was then stirred at room temperature for 24 hours. After the mixture was filtered, the filtrate was concentrated in vacuo and the concentrated liquid was poured into 50 ml of water. The mixture was extracted with carbon tetrachloride. After washing with water, the resultant mixture was dried with anhydrous magnesium sulfate and the solvent was then distilled off. Thus, 3.4 g (89% yield) of the desired compound No. 48 was obtained.
Reaction SMILES: [CH3:1][N:2]1[CH2:7][CH:6]=[C:5]([C:8]2[C:16]3[C:11](=[N:12][CH:13]=[CH:14][CH:15]=3)[NH:10][CH:9]=2)[CH2:4][CH2:3]1.[F:17][C:18]1[CH:26]=[CH:25][C:21]([C:22](Cl)=[O:23])=[CH:20][CH:19]=1>>[F:17][C:18]1[CH:26]=[CH:25][C:21]([C:22]([N:10]2[C:11]3[C:16](=[CH:15][CH:14]=[CH:13][N:12]=3)[C:8]([C:5]3[CH2:4][CH2:3][N:2]([CH3:1])[CH2:7][CH:6]=3)=[CH:9]2)=[O:23])=[CH:20][CH:19]=1
Reactant: CN1CC=C(c2c[nH]c3ncccc23)CC1
Reactant: O=C(Cl)c1ccc(F)cc1
Product: CN1CC=C(c2cn(C(=O)c3ccc(F)cc3)c3ncccc23)CC1

Procedure:
(10.1 mg, 26%); from 3-(1-methyl-1,2,3,6-tetrahydro-4-pyridinyl)-1H-7-azaindole (24.8 mg, 0.12 mmol) and 4-fluorobenzoyl chloride (28 μL, 0.24 mmol); HRMS-FAB+ for C20H18N3OF: calculated MH+: 336.15121. Found: 336.15100.
Reaction SMILES: [NH2:1][C:2]1[CH2:7][C:6]([CH3:9])([CH3:8])[CH2:5][C:4](=[O:10])[CH:3]=1.CO[CH:13](OC)[C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([O:20][C:21]2[CH:26]=[N:25][CH:24]=[CH:23][N:22]=2)[CH:15]=1>>[CH3:8][C:6]1([CH3:9])[CH2:7][C:2]2[NH:1][C:2]3[CH2:7][C:6]([CH3:9])([CH3:8])[CH2:5][C:4](=[O:10])[C:3]=3[CH:13]([C:14]3[CH:19]=[CH:18][CH:17]=[C:16]([O:20][C:21]4[CH:26]=[N:25][CH:24]=[CH:23][N:22]=4)[CH:15]=3)[C:3]=2[C:4](=[O:10])[CH2:5]1
Reactant: COC(OC)c1cccc(Oc2cnccn2)c1
Reactant: CC1(C)CC(=O)C=C(N)C1
Product: CC1(C)CC(=O)C2=C(C1)NC1=C(C(=O)CC(C)(C)C1)C2c1cccc(Oc2cnccn2)c1

Procedure:
Reaction of 3-amino-5,5-dimethyl-2-cyclohexen-1-one with 3-(2-pyrazinyloxy)-benzaldehyde dimethyl acetal in an analogous manner to that described in Example 1 gave 3,4,6,7,9,10-hexahydro-3,3,6,6-tetramethyl-9- [3-(2-pyrazinyloxy)phenyl]-1,8-(2H,5H)-acridinedione. Crystallization from dimethylformamide/water gave a pale brown crystalline solid of melting point 204-207° C.
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:10]=[C:11]([CH:14]([CH3:31])[C:15]([C:23]3[CH:28]=[CH:27][C:26]([F:29])=[CH:25][C:24]=3[F:30])([OH:22])[CH2:16][N:17]3[CH:21]=[N:20][CH:19]=[N:18]3)[S:12][CH:13]=2)=[CH:5][CH:4]=1)#[N:2].[C@@:32]12([CH2:42][S:43](O)(=[O:45])=[O:44])[C:39]([CH3:41])([CH3:40])[CH:36]([CH2:37][CH2:38]1)[CH2:35][C:33]2=[O:34]>CC(C)=O.CO>[C@@:32]12([CH2:42][S:43]([O:22][C@@:15]([C:23]3[CH:28]=[CH:27][C:26]([F:29])=[CH:25][C:24]=3[F:30])([C@H:14]([C:11]3[S:12][CH:13]=[C:9]([C:6]4[CH:7]=[CH:8][C:3]([C:1]#[N:2])=[CH:4][CH:5]=4)[N:10]=3)[CH3:31])[CH2:16][N:17]3[CH:21]=[N:20][CH:19]=[N:18]3)(=[O:45])=[O:44])[C:39]([CH3:41])([CH3:40])[CH:36]([CH2:37][CH2:38]1)[CH2:35][C:33]2=[O:34]
Reactant: CC(c1nc(-c2ccc(C#N)cc2)cs1)C(O)(Cn1cncn1)c1ccc(F)cc1F
Reactant: CC1(C)C2CC[C@]1(CS(=O)(=O)O)C(=O)C2
Solvent: CO
Solvent: CC(C)=O
Product: C[C@@H](c1nc(-c2ccc(C#N)cc2)cs1)[C@@](Cn1cncn1)(OS(=O)(=O)C[C@@]12CCC(CC1=O)C2(C)C)c1ccc(F)cc1F
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of racemic 3-[4-(4-cyanophenyl)thiazol-2-yl]-1-(1H-1,2,4-triazol-1-yl)-2-(2,4-difluorophenyl)-butan-2-ol (43.7 g) in acetone (800 ml) a solution of (1R)-10-camphorsulfonic acid (23 g) in methanol (300 ml) was added and the mixture was heated under reflux until a clear solution was obtained. The solution was slowly cooled to rt, seeded with crystals of the title enantiomeric salt and let overnight. The solid was collected by filtration, washed with acetone and dried to provide (2R,3R)-3-[4-(4-cyanophenyl)thiazol-2-yl]-1-(1H-1,2,4-triazol-1-yl)-2-(2,4-difluorophenyl)-butan-2-ol (1R)-10-camphorsulfonate as white solid. This crude salt was then taken up in methylenechloride (100 ml) and water (ca. 100 ml) and the mixture was basified with aqueous sodium hydroxide solution. The organic layer was separated and the aqueous phase washed twice with methylenechloride (50 ml) and combined. The organic phases were then washed twice with water (2×50 ml), dried with sodium sulfate, filtrated and the solvent removed under reduced pressure. The crude product was then mixed with isopropanol (ca. 150 ml), heated for 10 min, cooled to 0° C. and stirred for ca. 2 hrs. The product was collected, washed with isopropanol and dried under reduced pressure to provide the enantiomerically pure title compound (17.5 g, 41% yield, 99.1% ee); m.p. 164-166° C.; [α]=−30° (c=1, methanol, 25° C.); NMR (CDCl3): 1.23 (3H, d, J=8 Hz), 4.09 (1H, q, J=8 Hz), 4.26 (1H, d, J=14 Hz), 4.92 (1H, d, J=14 Hz), 5.75 (1H, s), 6.75-6.85 (2H, m), 7.45-7.54 (2H, m), 7.62 (1H, s), 7.69 (1H, s), 7.75 (1H, d, J=8 Hz), 7.86 (1H, s), 8.03 (1H, d, J=8 Hz). The analytical data were identical with published (U.S. Pat. No. 5,648,372 and Chem. Pharm. Bull. 1998, 46, 623-630).
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][C:6]([CH:10]=[O:11])=[CH:7][CH:8]=2)[CH:3]=[N:2]1.Br[CH2:13][C:14]1[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][C:15]=1[Cl:21]>>[Cl:21][C:15]1[CH:16]=[C:17]([Cl:20])[CH:18]=[CH:19][C:14]=1[CH2:13][N:1]1[C:9]2[C:4](=[CH:5][C:6]([CH:10]=[O:11])=[CH:7][CH:8]=2)[CH:3]=[N:2]1
Reactant: O=Cc1ccc2[nH]ncc2c1
Reactant: Clc1ccc(CBr)c(Cl)c1
Product: O=Cc1ccc2c(cnn2Cc2ccc(Cl)cc2Cl)c1

Procedure:
1-(2,4-Dichloro-benzyl)-1H-indazole-5-carbaldehyde was prepared from 1H-indazole-5-carbaldehyde and 1-bromomethyl-2,4-dichloro-benzene following General Procedure A.
Reaction SMILES: [CH2:1]([C:3]1[CH:9]=[C:8]([N:10]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:11]=[O:12])[CH:7]=[C:6]([CH2:19][CH3:20])[C:4]=1[NH2:5])[CH3:2].[C:21](Cl)(Cl)=[S:22].O.C(=O)([O-])[O-].[Ca+2]>ClCCl>[CH2:19]([C:6]1[CH:7]=[C:8]([N:10]([CH:11]=[O:12])[C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:9]=[C:3]([CH2:1][CH3:2])[C:4]=1[N:5]=[C:21]=[S:22])[CH3:20]
Reactant: CCc1cc(N(C=O)c2ccccc2)cc(CC)c1N
Reactant: S=C(Cl)Cl
Agent: O=C([O-])[O-]
Agent: [Ca+2]
Solvent: O
Solvent: ClCCl
Product: CCc1cc(N(C=O)c2ccccc2)cc(CC)c1N=C=S

Procedure:
With stirring, a solution of 24.0 g of 2,6-diethyl-4-(N-phenyl-N-formylamino)aniline in 80 ml of dichloromethane are added dropwise at 0° to 10° C. to 13.4 g of thiophosgene, 100 ml of dichloromethane, 60 ml of water and 19 g of calcium carbonate. The reaction mixture is stirred for 2 hours at room temperature and then filtered. The organic phase is separated, washed with 50 ml of water, dried over sodium sulfate and then concentrated by evaporation. The title compound of formula ##STR15## is obtained in the form of a crystalline powder which melts at 77°-78° C.
Reaction SMILES: ClS(O)(=O)=O.C1([C:12]2[C:13](=[O:23])[O:14][CH2:15][C:16]=2[C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)C=CC=CC=1>ClCCl>[C:17]1([C:16]2[CH2:15][O:14][C:13](=[O:23])[CH:12]=2)[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1
Reactant: O=C1OCC(c2ccccc2)=C1c1ccccc1
Agent: O=S(=O)(O)Cl
Solvent: ClCCl
Product: O=C1C=C(c2ccccc2)CO1
Temperature: 25 °C
Reaction time: 1 h
Yield: 98.3 %

Procedure:
To 20 mL of stirring chlorosulfonic acid cooled to −5° C. was added 3,4-diphenyl-2-(5H)-furanone (Step 1)(3.160 g, 13.4 mmol) portion-wise over 30 minutes. The solution was warmed to room temperature and maintained at that temperature for 16 hours. The reaction mixture was diluted with dichloromethane and quenched into ice water. The phases were separated and the aqueous phase extracted with dichloromethane, the combined dichloromethane extract was dried over anhydrous MgSO4, filtered and concentrated in vacuo. The residue was diluted with dichloromethane and added to excess concentrated NH4OH. The mixture was stirred for 1 hour. The phases were separated and the aqueous phase was extracted with dichloromethane. The organic extract was dried over anhydrous MgSO4, filtered and concentrated in vacuo to give a white solid that was crystallized from aqueous ethanol to afford pure 3-[(4-aminosulfonyl)phenyl)]-4-phenyl-2-(5H)-furanone (2.110 g, 50%): mp 225.5-226.5° C. 1H NMR (CDCl3/300 MHz) 7.79 (d, 2H, J=8.4 Hz), 7.41 (d, 2H, J=8.4 Hz), 6.38 (brs, 2H), 5.09 (s, 2H). FABLRMS m/z 316 (m+H). Anal. Calc'd for C16H13NO4S: C, 60.94; H, 4.16; N, 4.44. Found: C, 60.86; H, 4.18; N, 4.40.
Reaction SMILES: [CH:1]([O:4][C:5](=[O:28])[NH:6][C@@H:7]1[CH2:27][C:10]2[N:11]([CH2:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][N:22]=3)[C:12]3[CH:13]=[CH:14][C:15]([C:18]#N)=[CH:16][C:17]=3[C:9]=2[CH2:8]1)([CH3:3])[CH3:2].C[OH:30]>C(O)=O.O.[Ni].[Al]>[CH:1]([O:4][C:5](=[O:28])[NH:6][C@@H:7]1[CH2:27][C:10]2[N:11]([CH2:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][N:22]=3)[C:12]3[CH:13]=[CH:14][C:15]([CH:18]=[O:30])=[CH:16][C:17]=3[C:9]=2[CH2:8]1)([CH3:2])[CH3:3]
Reactant: CO
Reactant: CC(C)OC(=O)N[C@H]1Cc2c(n(Cc3ccccn3)c3ccc(C#N)cc23)C1
Agent: [Ni]
Agent: [Al]
Solvent: O=CO
Solvent: O
Product: CC(C)OC(=O)N[C@H]1Cc2c(n(Cc3ccccn3)c3ccc(C=O)cc23)C1
Temperature: 25 °C
Yield: 91 %

Procedure:
Dissolve (S)-(7-cyano-4-pyridin-2-ylmethyl-1,2,3,4-tetrahydro-cyclopenta[b]indol-2-yl)-carbamic acid isopropyl ester (200 mg, 0.53 mmol) in 88% formic acid (10 ml) and water (1 mL). Add aluminum-nickel catalyst (50/50 wt %) and heat at 90° C. for 24 h. Add water (1 mL) and heat for an additional 24 h. After cooling to room temperature, add methanol and filter off the catalyst through Celite®. Dilute with ethyl acetate and basify to pH=10 using 10% potassium carbonate. Separate the phases and wash the organic phase with 10% potassium carbonate. Dry the organic portion over anhydrous sodium sulfate, filter, and concentrate to obtain the title compound as an orange oil (181 mg, 91%). Use the crude product without further manipulation. MS (m/z): 378.2 (M+1).
Reaction SMILES: [N:1]1[CH:6]=[CH:5][C:4]([CH2:7][OH:8])=[CH:3][CH:2]=1.[N:9]1([C:14](N2C=CN=C2)=[O:15])[CH:13]=[CH:12][N:11]=[CH:10]1>C(Cl)Cl>[N:9]1([C:14]([O:8][CH2:7][C:4]2[CH:5]=[CH:6][N:1]=[CH:2][CH:3]=2)=[O:15])[CH:13]=[CH:12][N:11]=[CH:10]1
Reactant: O=C(n1ccnc1)n1ccnc1
Reactant: OCc1ccncc1
Solvent: ClCCl
Product: O=C(OCc1ccncc1)n1ccnc1
Yield: 80.7 %

Procedure:
A solution of (pyridin-4-yl)methanol (2.0 g, 18.3 mmol) and di(1H-imidazol-1-yl)methanone (5.94 g, 36.6 mmol) in 20 mL CH2Cl2 was heated overnight at 50° C. The reaction was quenched with water, extracted with CH2Cl2, dried over Na2SO4, filtered, and concentrated. Purification via silica gel chromatography using 10-70% EtOAc in CH2Cl2 gave (pyridin-4-yl)methyl 1H-imidazole-1-carboxylate (3 g, 81%). LC/MS: m/z 204.3 (M+H)+ at 0.38 min (v). 1H NMR (400 MHz, CDCl3) d 8.69 (dd, J=4.4, 1.6 Hz, 2H), 8.20 (t, J=0.9 Hz, 1H), 7.47 (t, J=1.5 Hz, 1H), 7.34 (dd, J=4.4, 1.6 Hz, 2H), 7.11 (dd, J=1.6, 0.8 Hz, 1H), 5.45 (s, 2H) ppm.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5](/[C:11](=[CH:14]/[C:15]2[S:16][C:17]([N:20]3[CH2:25][CH2:24][CH:23]([OH:26])[CH2:22][CH2:21]3)=[CH:18][CH:19]=2)/[C:12]#[N:13])[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].[Na+].[CH2:28]([N:30]([CH2:35][CH3:36])[CH2:31][C:32]([O-])=[O:33])[CH3:29].C1(C)C=CC(S(Cl)(=O)=O)=CC=1>N1C=CC=CC=1>[CH2:28]([N:30]([CH2:31][C:32]([O:26][CH:23]1[CH2:22][CH2:21][N:20]([C:17]2[S:16][C:15](/[CH:14]=[C:11](\[C:12]#[N:13])/[C:5]3[CH:6]=[CH:7][C:8]([O:9][CH3:10])=[C:3]([O:2][CH3:1])[CH:4]=3)=[CH:19][CH:18]=2)[CH2:25][CH2:24]1)=[O:33])[CH2:35][CH3:36])[CH3:29]
Reactant: COc1ccc(/C(C#N)=C/c2ccc(N3CCC(O)CC3)s2)cc1OC
Reactant: CCN(CC)CC(=O)[O-]
Agent: Cc1ccc(S(=O)(=O)Cl)cc1
Agent: [Na+]
Solvent: c1ccncc1
Product: CCN(CC)CC(=O)OC1CCN(c2ccc(/C=C(\C#N)c3ccc(OC)c(OC)c3)s2)CC1
Temperature: 25 °C
Reaction time: 1 h
Yield: 74.9 %

Procedure:
Compound 6 (3.70 g) was dissolved in pyridine (100 mL), and N,N-diethylglycin sodium salt (7.66 g) was added to the solution, followed by stirring at room temperature for 1 hour. Subsequently, p-toluenesulfonyl chloride (9.43 g) was added to the mixture, followed by stirring under reflux for 12 hours. After completion of reaction, the solvent was evaporated under reduced pressure. Chloroform (1,000 mL) was added to the residue, and the mixture was washed with water three times. The pH of the aqueous layer was checked by use of a pH testpaper, and adjusted to 4 to 5 with 1N aqueous hydrochloric acid. The organic layer was dried over sodium sulfate anhydrate, and the solvent was evaporated to dryness. The residue was purified by silica gel column chromatography (CHCl3-Hexane), to thereby yield the target product (yield: 3.62 g, 75%).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[C@@H:12]([CH:13]=O)[CH2:11][O:10][C:9]1([CH3:16])[CH3:15])=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:17]([CH:22]=P(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)([O:19][CH2:20][CH3:21])=[O:18]>C1(C)C=CC=CC=1>[C:1]([O:5][C:6]([N:8]1[C@@H:12](/[CH:13]=[CH:22]/[C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH2:11][O:10][C:9]1([CH3:16])[CH3:15])=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: CCOC(=O)C=P(c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: CC(C)(C)OC(=O)N1[C@@H](C=O)COC1(C)C
Solvent: Cc1ccccc1
Product: CCOC(=O)/C=C/[C@H]1COC(C)(C)N1C(=O)OC(C)(C)C
Yield: 111.3 %

Procedure:
A mixture comprising (4R)-4-formyl-2,2-dimethyl-1,3-oxazolidine-3-carboxylic acid tert-butyl ester (11.7 g), (carbethoxymethylene)triphenylphosphorane (20.7 g), and toluene (100 mL) was stirred at 100° C. for 18 hours. The reaction mixture was concentrated, and the residue was purified by silica gel column chromatography (hexane:ethyl acetate=8:1), to thereby give the title compound (17 g).
Reaction SMILES: [CH:1]1([N:4]2[C:13]3[C:8](=[CH:9][C:10]([F:16])=[C:11](F)[C:12]=3[F:14])[C:7](=[O:17])[C:6]([C:18]([OH:20])=[O:19])=[CH:5]2)[CH2:3][CH2:2]1.Br.Br.[C:23]12[CH2:30][NH:29][CH2:28][C:27]=1[CH2:26][NH:25][CH2:24]2.N12CCCN=C1CCCCC2>C(#N)C>[CH:1]1([N:4]2[C:13]3[C:8](=[CH:9][C:10]([F:16])=[C:11]([N:25]4[CH2:26][C:27]5[CH2:28][NH:29][CH2:30][C:23]=5[CH2:24]4)[C:12]=3[F:14])[C:7](=[O:17])[C:6]([C:18]([OH:20])=[O:19])=[CH:5]2)[CH2:2][CH2:3]1
Reactant: C1NCC2=C1CNC2
Reactant: O=C(O)c1cn(C2CC2)c2c(F)c(F)c(F)cc2c1=O
Agent: Br
Solvent: CC#N
Solvent: C1CCC2=NCCCN2CC1
Product: O=C(O)c1cn(C2CC2)c2c(F)c(N3CC4=C(CNC4)C3)c(F)cc2c1=O
Temperature: 100 °C
Reaction time: 8 h
Yield: 66.4 %

Procedure:
0.4 g of 1-cyclopropyl-6,7,8-trifluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid, 0.8 g of 3,7-diazabicyclo[3.3.0]oct-1(5)-ene dihydrobromide and 0.8 ml of 1,8-diazabicyclo[5.4.0] undec-7-ene (DBU) were suspended in 30 ml of acetonitrile and the suspension was refluxed in 100° C. oil bath for 8 hours. The reaction mixture was kept overnight at room temperature. The produced precipitate was filtered and washed with methanol. 0.35 g of the title compound was obtained (yield 67%)
Reaction SMILES: [CH:1]1[C:14]2[C:5](=[CH:6][C:7]3[C:12]([CH:13]=2)=[CH:11][CH:10]=[CH:9][CH:8]=3)[CH:4]=[CH:3][CH:2]=1.[CH2:15]([Cl:18])[CH:16]=[CH2:17]>C1C=CC=CC=1>[Cl:18][CH2:15][CH:16]1[CH:6]2[C:7]3[CH:8]=[CH:9][CH:10]=[CH:11][C:12]=3[CH:13]([C:14]3[C:5]2=[CH:4][CH:3]=[CH:2][CH:1]=3)[CH2:17]1
Reactant: c1ccc2cc3ccccc3cc2c1
Reactant: C=CCCl
Solvent: c1ccccc1
Product: ClCC1CC2c3ccccc3C1c1ccccc12
Temperature: 220 °C

Procedure:
Anthracene (75 gm) was combined with allyl chloride (150 gm) and benzene (375 gm) in a Parr bomb and heated to 220° C. for 13 hours. The contents were filtered and the benzene was removed on a rotary evaporator. The residue was recrystallized from ethanol to provide the product as a white solid (mp=108°-111° C.).
Reaction SMILES: [Br:1][C:2]1[C:14](=[O:15])[N:13]([CH:16]2[CH2:20][CH2:19][CH2:18][CH2:17]2)[C:5]2[N:6]=[C:7](S(C)=O)[N:8]=[CH:9][C:4]=2[C:3]=1[CH3:21].[CH3:22][CH:23]1[O:28][CH:27]([CH3:29])[CH2:26][N:25]([C:30]2[CH:31]=[CH:32][C:33]([NH2:36])=[N:34][CH:35]=2)[CH2:24]1>C1(C)C=CC=CC=1>[Br:1][C:2]1[C:14](=[O:15])[N:13]([CH:16]2[CH2:20][CH2:19][CH2:18][CH2:17]2)[C:5]2[N:6]=[C:7]([NH:36][C:33]3[CH:32]=[CH:31][C:30]([N:25]4[CH2:26][CH:27]([CH3:29])[O:28][CH:23]([CH3:22])[CH2:24]4)=[CH:35][N:34]=3)[N:8]=[CH:9][C:4]=2[C:3]=1[CH3:21]
Reactant: Cc1c(Br)c(=O)n(C2CCCC2)c2nc(S(C)=O)ncc12
Reactant: CC1CN(c2ccc(N)nc2)CC(C)O1
Solvent: Cc1ccccc1
Product: Cc1c(Br)c(=O)n(C2CCCC2)c2nc(Nc3ccc(N4CC(C)OC(C)C4)cn3)ncc12
Temperature: 25 °C
Yield: 25.8 %

Procedure:
6-Bromo-8-cyclopentyl-2-methanesulfinyl-5-methyl-8H-pyrido[2,3-d]pyrimidin-7-one (1.0 g, 2.70 mmol) and 5-(2,6-dimethyl-morpholin-4-yl)-pyridin-2-ylamine (0.668 g, 3.73 mmol) were heated to reflux in toluene (10 mL) for 16 hours. The reaction mixture was cooled to room temperature and the precipitate that formed was collected by filtration and washed on the funnel with toluene (3×10 mL) to give 6-bromo-8-cyclopentyl-2-[5-(2,6-dimethyl-morpholin-4-yl )-pyridin-2-ylamino]-5-methyl-8H-pyrido[2,3-d]pyrimidin-7-one as a brown solid (0.358 g, 27.3%). MS (APCl) Calc'd for M+1: 513.2. Found: 513.1. Anal. Calc'd for C24H29BrN6O2: C, 56.14; H, 5.69; N, 16.37. Found; C, 55.90; H, 5.62; N, 16.10.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[CH:4][C:3]=1[N:16]1[C:21]2[N:22]=[C:23]([S:26][CH3:27])[N:24]=[CH:25][C:20]=2[CH:19]=[CH:18][C:17]1=[O:28].C1C=C(Cl)C=C(C(OO)=[O:37])C=1.O.C([O-])([O-])=O.[Na+].[Na+]>C(Cl)Cl>[F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[CH:4][C:3]=1[N:16]1[C:21]2[N:22]=[C:23]([S:26]([CH3:27])=[O:37])[N:24]=[CH:25][C:20]=2[CH:19]=[CH:18][C:17]1=[O:28]
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: CSc1ncc2ccc(=O)n(-c3cc(NC(=O)OC(C)(C)C)ccc3F)c2n1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: ClCCl
Product: CS(=O)c1ncc2ccc(=O)n(-c3cc(NC(=O)OC(C)(C)C)ccc3F)c2n1
Temperature: 0 °C
Reaction time: 1 h
Yield: 131.6 %

Procedure:
At 0° C., a suspension of tert-butyl (4-fluoro-3-(2-(methylthio)-7-oxopyrido[2,3-d]pyrimidin-8(7H)-yl)phenyl)carbamate (59) (270 mg, 0.67 mmol) in DCM (10 mL) was treated with MCPBA (77 wt. %, 161 mg, 0.72 mmol) in one portion and stirred at 0° C. for 1 h. The reaction mixture was diluted with DCM (50 mL), and treated with ice and water (30 mL) followed by 10% Na2CO3 (ca. 10 mL). The DCM layer was separated and the aqueous layer was extracted with an additional amount of DCM (2×50 mL), dried over Na2SO4 and concentrated to give crude tert-butyl (4-fluoro-3-(2-(methylsulfinyl)-7-oxopyrido[2,3-d]pyrimidin-8(7H)-yl)phenyl)carbamate (60) (369 mg) as a light yellow solid. m/z (ESI, +ve ion) 440.9 (M+Na)+. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.63 (1H, br. s.), 8.24 (1H, d, J=9.6 Hz), 7.68 (1H, d, J=3.5 Hz), 7.44-7.52 (1H, m), 7.33-7.41 (1H, m), 6.95-7.01 (1H, m), 5.76 (1H, s), 2.72-2.78 (3H, m), 1.47 (9H, s). 19F NMR (376 MHz, DMSO-d6) δ ppm-129.58 (1F, s).
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([NH:10][C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([N+:17]([O-:19])=[O:18])[CH:12]=2)=[CH:6][C:5]=1[CH2:20][C:21]([OH:23])=[O:22])([O-:3])=[O:2].OS(O)(=O)=O.[CH3:29][CH2:30]O>>[CH2:29]([O:22][C:21](=[O:23])[CH2:20][C:5]1[CH:6]=[C:7]([NH:10][C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([N+:17]([O-:19])=[O:18])[CH:12]=2)[CH:8]=[CH:9][C:4]=1[N+:1]([O-:3])=[O:2])[CH3:30]
Reactant: O=C(O)Cc1cc(Nc2cccc([N+](=O)[O-])c2)ccc1[N+](=O)[O-]
Reactant: CCO
Agent: O=S(=O)(O)O
Product: CCOC(=O)Cc1cc(Nc2cccc([N+](=O)[O-])c2)ccc1[N+](=O)[O-]

Procedure:
A solution of [2-nitro-5-(3-nitro-phenylamino)-phenyl]-acetic acid (0.49 g, 1.5 mmol) in EtOH (20 ml) is refluxed in the presence of 0.2 ml concentrated H2SO4 for 3 hours before it is concentrated. To the residue is added saturated NaHCO3. The mixture is extracted with ethyl acetate (30 ml×3). The organic layers are combined and dried with Na2SO4 to give [2-nitro-5-(3-nitro-phenylamino)-phenyl]-acetic acid ethyl ester: LC-MS: 346.0 (MH+).
Reaction SMILES: [C:1]([N:9]=[C:10]=[S:11])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:12][C@@:13]1([C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([F:30])[C:25]=2[F:31])[CH2:17][O:16][C@H:15]([C:18]([F:21])([F:20])[F:19])[C@H:14]1[CH2:22][OH:23].C(=O)(O)[O-].[Na+]>C(Cl)Cl>[F:31][C:25]1[C:26]([F:30])=[CH:27][CH:28]=[CH:29][C:24]=1[C@@:13]1([NH:12][C:10]([NH:9][C:1](=[O:8])[C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[S:11])[C@H:14]([CH2:22][OH:23])[C@@H:15]([C:18]([F:21])([F:19])[F:20])[O:16][CH2:17]1
Reactant: N[C@@]1(c2cccc(F)c2F)CO[C@H](C(F)(F)F)[C@H]1CO
Reactant: O=C(N=C=S)c1ccccc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Product: O=C(NC(=S)N[C@@]1(c2cccc(F)c2F)CO[C@H](C(F)(F)F)[C@H]1CO)c1ccccc1
Temperature: 25 °C
Reaction time: 18 h

Procedure:
Benzoyl isothiocyanate (2.0 mL) was added to a solution containing ((2S,3R,4S)-4-amino-4-(2,3-difluorophenyl)-2-(trifluoromethyl)tetrahydrofuran-3-yl)methanol (3.12 g) in DCM (20 mL), and the mixture was stirred at RT for 18 h. Sodium bicarbonate (sat., aq., 50 mL) was then added, the mixture extracted with EtOAc (3×75 mL), dried over MgSO4 and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (5% to 40% EtOAc in hexanes) to obtain the title compound (4.18 g). 1H NMR (400 MHz, CDCl3) δ ppm 3.12 (dd, J=7.6, 4.3 Hz, 1H), 3.18-3.29 (m, 1H), 4.03 (ddd, J=12.3, 7.2, 4.5 Hz, 1H), 4.35-4.49 (m, 1H), 4.59 (d, J=9.9 Hz, 1H), 4.81 (d, J=9.6 Hz, 1H), 7.07-7.23 (m, 2H), 7.49 (t, J=7.2 Hz, 1H), 7.56 (t, J=7.7 Hz, 2H), 7.67 (t, J=7.5 Hz, 1H), 7.88 (d, J=7.1 Hz, 2H), 8.92 (s, 1H), 11.89 (s, 1H)
Reaction SMILES: [Zn](CC)[CH2:2]C.C(I)I.[CH2:9]([N:16]1[CH2:21][CH2:20][CH:19]=[C:18]([CH2:22][OH:23])[CH2:17]1)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.Cl>C(Cl)Cl>[CH2:9]([N:16]1[CH2:21][CH2:20][CH:19]2[C:18]([CH2:22][OH:23])([CH2:2]2)[CH2:17]1)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1
Reactant: CC[Zn]CC
Reactant: OCC1=CCCN(Cc2ccccc2)C1
Agent: Cl
Solvent: ICI
Solvent: ClCCl
Product: OCC12CC1CCN(Cc1ccccc1)C2
Reaction time: 0.25 h

Procedure:
To a solution of ZnEt2 (17.3 ml, 1.0 M) in CH2Cl2 (20 ml) at 0° C. was added CH2I2 (1.4 ml) (CAUTION: exothermic!). After stirring for 15 min, a solution of 172 (352 mg, 1.73 mmol) in CH2Cl2 (2 ml) was added. The mixture was stirred from 0° C. to room temperature overnight. 5% HCl was added to bring the mixture to a homogeneous solution. (white solid dissolved). The two layers were separated. Aqueous layer was neutralized with 2N KOH to pH=10–12, extracted with CH2Cl2 (twice). The combined organic solution was dried (K2CO3/Na2SO4), filtered and concentrated. The LRMS of the crude mixture showed that the ratio of 173 to 172 was about 1:1. The product was not isolated from the starting material due to their similar polarities. LRMS (calculated for C14H19NO) 217. found 217.