Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([N:3]1[C:12]2[C:7](=[CH:8][C:9]([F:15])=[C:10](F)[C:11]=2[F:13])[C:6](=[O:16])[C:5]([C:17]([O:19]CC)=[O:18])=[CH:4]1)[CH3:2].[CH3:22][CH:23]1[CH2:28][NH:27][CH2:26][CH2:25][NH:24]1>N1C=CC=CC=1>[CH2:1]([N:3]1[C:12]2[C:7](=[CH:8][C:9]([F:15])=[C:10]([N:27]3[CH2:26][CH2:25][NH:24][CH:23]([CH3:22])[CH2:28]3)[C:11]=2[F:13])[C:6](=[O:16])[C:5]([C:17]([OH:19])=[O:18])=[CH:4]1)[CH3:2]
Reactant: CC1CNCCN1
Reactant: CCOC(=O)c1cn(CC)c2c(F)c(F)c(F)cc2c1=O
Solvent: c1ccncc1
Product: CCn1cc(C(=O)O)c(=O)c2cc(F)c(N3CCNC(C)C3)c(F)c21
Yield: 56.8 %

Procedure:
A mixture of 1.50 g of ethyl 1-ethyl-6,7,8-trifluoro-1,4-dihydro-4-oxoquinoline-3-carboxylate, 1.50 g of 2-methylpiperazine and 5 ml of pyridine was heated for 3 hours under reflux. The solvent of the reaction mixture was evaporated and the residue was dissolved in chloroform. The solution was washed with water, dried and evaporated. The residue was recrystallized from a mixture of benzene and isopropyl ether to give 1.00 g of the title compound as colorless needles, M.p. 126.5°-127.5° C.
Reaction SMILES: [C:1]1([C:7]2([NH2:13])[CH2:12][CH2:11][CH2:10][NH:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:14][C:15]([CH3:17])=O.C[Si]([C:22]#[N:23])(C)C.[OH-].[Na+]>C(O)(=O)C.ClCCl>[NH2:13][C:7]1([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[CH2:12][CH2:11][CH2:10][N:9]([C:15]([CH3:17])([CH3:14])[C:22]#[N:23])[CH2:8]1
Reactant: C[Si](C)(C)C#N
Reactant: NC1(c2ccccc2)CCCNC1
Reactant: CC(C)=O
Agent: [Na+]
Agent: [OH-]
Solvent: CC(=O)O
Solvent: ClCCl
Product: CC(C)(C#N)N1CCCC(N)(c2ccccc2)C1
Temperature: 25 °C
Reaction time: 0.08 h
Yield: 76.1 %

Procedure:
To a solution of 300 mg (1.701 mmol) rac-3-Phenyl-piperidin-3-ylamine in 1.3 ml acetic acid, was added dropwise 188 ul (2.553 mmol) acetone. The mixture was stirred at room temperature for 5 minutes. 320 ul (2.553 mmol) trimethylsilyl cyanide was added dropwise. The temperature rose to 31° C. The mixture was stirred at room temperature for 4 hours. The mixture was diluted with dichloromethane and cooled to 0° C. NaOH 2N was added dropwise to basify the mixture. The organic layer was separated and the aqueous layer was extracted twice with dichloromethane. The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo to provide 315 mg (76.1%) of the title compound as a yellow oil.
Reaction SMILES: [C:1]1([C:7]2([C:12]3[S:16][C:15]([CH:17]4[O:21][C:20](=[O:22])[NH:19][C:18]4=[O:23])=[CH:14][CH:13]=3)OCC[O:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CCOCC.Cl>C(OCC)(=O)C>[C:7]([C:12]1[S:16][C:15]([CH:17]2[O:21][C:20](=[O:22])[NH:19][C:18]2=[O:23])=[CH:14][CH:13]=1)(=[O:8])[C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: O=C1NC(=O)C(c2ccc(C3(c4ccccc4)OCCO3)s2)O1
Agent: Cl
Solvent: CCOC(C)=O
Solvent: CCOCC
Product: O=C1NC(=O)C(c2ccc(C(=O)c3ccccc3)s2)O1

Procedure:
5-[5-(2-Phenyl-1,3-dioxolan-2-yl)-2-thienyl]-oxazolidine-2,4-dione (0.40 g.) was dissolved in 30 ml. of ether and stirred with 10 ml. of 6 N hydrochloric acid at room temperature for 1 hour. Ethyl acetate (10 ml.) was added, and the organic layer was separated and evaporated in vacuo to dryness (0.388 g.). Chromatography on 50 ml. of silica gel, eluted with 1:1 hexane:ethyl acetate/5% acetic acid and monitored by tlc, gave in early fractions purified 5-(5-benzoyl-2-thienyl)oxazolidine-2,4-dione (0.22 g., m.p. 153°-155° C., m/e 287).
Reaction SMILES: [NH:1](C(OC(C)(C)C)=O)[C@H:2]([C:10]([NH:12][C@H:13]([C:18]([O:20][CH3:21])=[O:19])[CH2:14][CH2:15][S:16][CH3:17])=[O:11])[CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.C1(OC)C=CC=CC=1.[ClH:37]>CCOC(C)=O.CCCCCC>[NH2:1][C@H:2]([C:10]([NH:12][C@H:13]([C:18]([O:20][CH3:21])=[O:19])[CH2:14][CH2:15][S:16][CH3:17])=[O:11])[CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[ClH:37]
Reactant: COC(=O)[C@H](CCSC)NC(=O)[C@H](Cc1ccccc1)NC(=O)OC(C)(C)C
Agent: Cl
Solvent: CCCCCC
Solvent: COc1ccccc1
Solvent: CCOC(C)=O
Product: COC(=O)[C@H](CCSC)NC(=O)[C@@H](N)Cc1ccccc1
Temperature: 0 °C

Procedure:
To an ice cold solution of 16.42 g of Boc-Phe-Met-OCH3 and 21.7 ml of anisole in 200 ml of EtOAc was introduced hydrogen chloride for 30 min. Evaporation of the solution gave a residue which was dissolved in 100 ml of EtOAc and diluted with 400 ml of hexane to give H-Phe-Met-OCH3.HCl which was used without further purification.
Reaction SMILES: [C:1]([C:9]1[CH:36]=[CH:35][C:12]2[N:13]([CH2:17][CH2:18][O:19][C:20]3[CH:25]=[CH:24][C:23]([CH2:26][CH:27]([O:32][CH2:33][CH3:34])[C:28]([O:30][CH3:31])=[O:29])=[CH:22][CH:21]=3)[C:14](=[O:16])[S:15][C:11]=2[CH:10]=1)(=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:37]([O:41][NH2:42])([CH3:40])([CH3:39])[CH3:38]>>[C:37]([O:41][N:42]=[C:1]([C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[C:9]1[CH:36]=[CH:35][C:12]2[N:13]([CH2:17][CH2:18][O:19][C:20]3[CH:21]=[CH:22][C:23]([CH2:26][CH:27]([O:32][CH2:33][CH3:34])[C:28]([O:30][CH3:31])=[O:29])=[CH:24][CH:25]=3)[C:14](=[O:16])[S:15][C:11]=2[CH:10]=1)([CH3:40])([CH3:39])[CH3:38]
Reactant: CC(C)(C)ON
Reactant: CCOC(Cc1ccc(OCCn2c(=O)sc3cc(C(=O)c4ccccc4)ccc32)cc1)C(=O)OC
Product: CCOC(Cc1ccc(OCCn2c(=O)sc3cc(C(=NOC(C)(C)C)c4ccccc4)ccc32)cc1)C(=O)OC

Procedure:
Starting from the compound obtained in Step C of Example 1, the procedure is as in Step B of Example 2, replacing the hydroxylamine by O-(tert-butyl)hydroxylamine.
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([NH:8][C@H:9]([C:11]2[N:16]=[C:15]3[CH:17]=[CH:18][N:19]([CH3:20])[C:14]3=[CH:13][C:12]=2[N:21]2[CH2:26][CH2:25][CH2:24][C@@H:23]([N:27]3C(=O)C4C(=CC=CC=4)C3=O)[CH2:22]2)[CH3:10])[C:5]([C:38]#[N:39])=[C:4]([CH3:40])[N:3]=1.O.NN.NN>C(O)C.C(#N)C>[NH2:1][C:2]1[N:7]=[C:6]([NH:8][C@H:9]([C:11]2[N:16]=[C:15]3[CH:17]=[CH:18][N:19]([CH3:20])[C:14]3=[CH:13][C:12]=2[N:21]2[CH2:26][CH2:25][CH2:24][C@@H:23]([NH2:27])[CH2:22]2)[CH3:10])[C:5]([C:38]#[N:39])=[C:4]([CH3:40])[N:3]=1
Reactant: Cc1nc(N)nc(N[C@@H](C)c2nc3ccn(C)c3cc2N2CCC[C@@H](N3C(=O)c4ccccc4C3=O)C2)c1C#N
Agent: NN
Solvent: O
Solvent: CC#N
Solvent: CCO
Product: Cc1nc(N)nc(N[C@@H](C)c2nc3ccn(C)c3cc2N2CCC[C@@H](N)C2)c1C#N
Temperature: 60 °C
Yield: 26.7 %

Procedure:
To a 25 mL pear flask were added 2-amino-4-(((S)-1-(6-((R)-3-(1,3-dioxoisoindolin-2-yl)piperidin-1-yl)-1-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)ethyl)amino)-6-methylpyrimidine-5-carbonitrile (20 mg, 0.037 mmol) and hydrazine monohydrate (0.027 mL, 0.56 mmol) in ethanol (1 mL). The mixture was heated to 60° C. for 8 hours and then at room temperature overnight. Additional hydrazine (30 eq, 0.054 mL) was added and the mixture was heated for another 4 hours. The crude reaction mixture was diluted with acetonitrile and was then purified by preparative HPLC (basic mode, 20-45% ACN/water gradient). The product-containing fractions were combined and lyophilized to give the title compound as a light brown solid (4.0 mg, 28%). The absolute configuration of the stereocenter on the piperidine ring was not determined, but was assigned the opposite configuration of EXAMPLE 5. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.41 (d, J=6.57 Hz, 3H), 1.72-1.99 (m, 3H), 2.09-2.22 (m, 1H), 2.27-2.36 (m, 3H), 2.56-2.73 (m, 3H), 3.47 (ddd, J=9.09, 7.20, 4.93 Hz, 1H), 3.59-3.66 (m, 1H), 3.67-3.73 (m, 3H), 5.19 (br s, 2H), 5.77-5.95 (m, 1H), 6.57 (d, J=3.28 Hz, 1H), 6.93-7.07 (m, 1H), 7.12-7.16 (m, 1H), 7.17-7.23 (m, 2H), 7.40 (s, 1H); ESI-MS m/z [M+H]+ calc'd for C21H27N9, 406. found 406.
Reaction SMILES: [CH3:1][N:2]1[CH2:25][CH2:24][C:5]2=[C:6]([S:13][C:14]3[CH:23]=[CH:22][C:17]([C:18](OC)=[O:19])=[CH:16][CH:15]=3)[C:7]3[C:12]([N:4]2[CH2:3]1)=[CH:11][CH:10]=[CH:9][CH:8]=3.[NH2:26][OH:27].Cl.C[O-].[Na+]>CO>[OH:27][NH:26][C:18](=[O:19])[C:17]1[CH:22]=[CH:23][C:14]([S:13][C:6]2[C:7]3[C:12](=[CH:11][CH:10]=[CH:9][CH:8]=3)[N:4]3[CH2:3][N:2]([CH3:1])[CH2:25][CH2:24][C:5]=23)=[CH:15][CH:16]=1
Reactant: COC(=O)c1ccc(Sc2c3n(c4ccccc24)CN(C)CC3)cc1
Reactant: NO
Agent: C[O-]
Agent: Cl
Agent: [Na+]
Solvent: CO
Product: CN1CCc2c(Sc3ccc(C(=O)NO)cc3)c3ccccc3n2C1
Temperature: 25 °C
Reaction time: 4 h
Yield: 29.9 %

Procedure:
To a solution of methyl 4-((2-methyl-1,2,3,4-tetrahydropyrimido[1,6-a]indol-5-yl)thio)benzoate (0.4 g) and NH2OH.HCl (0.63 g) in 4 mL of dry MeOH was added 2.5 mL of 25% NaOMe solution in methanol. The reaction mixture was stirred for 4 h at r.t. and then quenched with 10 mL of potassium phosphate buffer solution. The mixture was extracted 40 mL of EtOAc. The extract was dried over Na2SO4, filtered and concentrated. The residue was purified by silica gel chromatography eluted with up to 10% MeOH/CH2Cl2 to give 0.12 g of the title product as white solid.
Reaction SMILES: [Br:1]Br.[CH3:3][O:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:16]=[CH:15][C:14]([CH:17]=[O:18])=[CH:13][CH:12]=2)=[CH:7][CH:6]=1>CC(O)=O>[Br:1][C:10]1[CH:9]=[C:8]([C:11]2[CH:16]=[CH:15][C:14]([CH:17]=[O:18])=[CH:13][CH:12]=2)[CH:7]=[CH:6][C:5]=1[O:4][CH3:3]
Reactant: COc1ccc(-c2ccc(C=O)cc2)cc1
Reactant: BrBr
Solvent: CC(=O)O
Product: COc1ccc(-c2ccc(C=O)cc2)cc1Br
Temperature: 25 °C
Reaction time: 16 h
Yield: 96 %

Procedure:
Bromine (8.2 mL, 0.160 mol) in 40 mL of glacial HOAc was added under nitrogen dropwise over 30 minutes to a solution of 4′-methoxy-1,1′-biphenyl-4-carbaldehyde (31.0g, 0.146 mol), prepared in the previous step, in 500 mL of glacial HOAc at room temperature. After the addition the reaction was stirred at room temperature for 16 h. During the reaction a solid precipitated. The solid can be collected by filtration. If by TLC starting material remains in either the solid or filtrate the solid can be redissolved and additional bromine added until the reaction is complete. When the reaction is complete by TLC, water is added and the solid present is collected by filtration to give 3′-bromo-4′-methoxy-1,1′-biphenyl-4-carbaldehyde (40.8 g, 96%) as a white solid, MS (ESI) m/z 290. Elemental Analysis for C14H11BrO2. Calc'd: C, 57.76; H, 3.81; N, 0.00. Found: C, 57.30; H, 3.61; N, 0.00.
Reaction SMILES: [Cl:1][C:2]1[C:3]([C:23]([F:26])([F:25])[F:24])=[CH:4][C:5]2[N:9]=[C:8]([CH2:10][CH3:11])[N:7]([C:12]3[CH:17]=[CH:16][C:15]([CH2:18][CH:19](O)[CH3:20])=[CH:14][CH:13]=3)[C:6]=2[CH:22]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P([N:60]=[N+:61]=[N-:62])(C2C=CC=CC=2)=O)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>O1CCCC1.C(OCC)(=O)C>[N:60]([CH:19]([CH3:20])[CH2:18][C:15]1[CH:16]=[CH:17][C:12]([N:7]2[C:6]3[CH:22]=[C:2]([Cl:1])[C:3]([C:23]([F:26])([F:25])[F:24])=[CH:4][C:5]=3[N:9]=[C:8]2[CH2:10][CH3:11])=[CH:13][CH:14]=1)=[N+:61]=[N-:62]
Reactant: CCc1nc2cc(C(F)(F)F)c(Cl)cc2n1-c1ccc(CC(C)O)cc1
Reactant: [N-]=[N+]=NP(=O)(c1ccccc1)c1ccccc1
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: CCc1nc2cc(C(F)(F)F)c(Cl)cc2n1-c1ccc(CC(C)N=[N+]=[N-])cc1
Reaction time: 3 h
Yield: 36.8 %

Procedure:
To a stirred solution of 1-{4-[6-chloro-2-ethyl-5-(trifluoromethyl)-1H-benzimidazol-1-yl]phenyl}-2-propanol (step 8 of Example 247, 1.96 g, 5.12 mmol), triphenylphosphine (1.75 g, 6.66 mmol) and diphenylphosphoryl azide (1.83 mg, 6.66 mmol) in tetrahydrofuran (15 ml) was added diethyl azodicarboxylate (1.16 mg, 6.66 mmol) at room temperature. The resulting mixture was stirred at temperature for 3 h, then under reflux temperature. The mixture was diluted with ethyl acetate and washed with water and brine. The organic layer was dried (Na2SO4), and concentrated. Purification by flash column chromatography eluting with hexane/ethyl acetate (2:1) and TLC developing with hexane/ethyl acetate (1:1) afforded 769 mg (37%) of the title compound as a slight yellow syrup.
Reaction SMILES: C([C:4]1[CH:13]=[CH:12][C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]=1C(C)C)(C)C.C(C1C=CC2C(=CC=C(C(C)C)C=2)C=1)(C)C>C(C1C=CC2C(=CC(C(C)C)=CC=2)C=1)(C)C>[CH:10]1[C:11]2[C:6](=[CH:5][CH:4]=[CH:13][CH:12]=2)[CH:7]=[CH:8][CH:9]=1
Reactant: CC(C)c1ccc2ccccc2c1C(C)C
Agent: CC(C)c1ccc2cc(C(C)C)ccc2c1
Agent: CC(C)c1ccc2ccc(C(C)C)cc2c1
Product: c1ccc2ccccc2c1

Procedure:
Naphthalene (80 g) and the catalyst from example 1 (4 g or 5% by weight on the naphthalene) are contacted with propylene at a temperature of 220° C. with an added pressure of propylene of 0.8×105Pa for 3 hours in a 300 ml Parr pressure autoclave operated under agitation. Analysis of the reaction mixture by gas chromatography gives a conversion of 89.0%, a yield in the 2,6-diisopropyl naphthalene of 34.4% and a yield in 2,7-diisopropyl naphthalene of 11.8%. The sum of the diisopropyl naphthalene represents 51.7% of the conversion. The selectivity to the 2,6-diisopropyl naphthalene is 38.7% and the selectivity to the 2,7-diisopropyl naphthalene is 13.3%.
Reaction SMILES: [NH:1]1[C:8]2[N:4]([N:5]=[CH:6][CH:7]=2)[CH2:3][CH2:2]1.[Br:9]Br>C(O)(=O)C>[BrH:9].[Br:9][C:7]1[CH:6]=[N:5][N:4]2[CH2:3][CH2:2][NH:1][C:8]=12
Reactant: BrBr
Reactant: c1cc2n(n1)CCN2
Solvent: CC(=O)O
Product: Br
Product: Brc1cnn2c1NCC2
Temperature: 25 °C
Reaction time: 3 h
Yield: 71.5 %

Procedure:
A 100-mL round-bottom flask was charged with 2,3-dihydro-1H-imidazo[1,2-b]pyrazole (1.7 g, 15.6 mmol) and acetic acid (5 mL). A solution of bromine (7.39 g, 46.2 mmol) in acetic acid (47 mL) was then added slowly. The resulting solution stirred for 3 h at room temperature. The reaction mixture was filtered and the filtrate was concentrated under vacuum to afford 7-bromo-2,3-dihydro-1H-imidazo[1,2-b]pyrazole hydrobromide (3.0 g, 72%) as a yellow solid. MS (ESI, pos. ion) m/z 188, 190 [M+H]+.
Reaction SMILES: [C:1]([CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][NH:20][C:21]1[CH:28]=[CH:27][C:24]([C:25]#[N:26])=[CH:23][CH:22]=1)([O:3]C)=[O:2].[OH-].[K+].C(O)C.Cl>O>[C:1]([CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][NH:20][C:21]1[CH:28]=[CH:27][C:24]([C:25]#[N:26])=[CH:23][CH:22]=1)([OH:3])=[O:2]
Reactant: COC(=O)CCCCCCCCCCCCCCCNc1ccc(C#N)cc1
Agent: Cl
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: N#Cc1ccc(NCCCCCCCCCCCCCCCC(=O)O)cc1

Procedure:
A solution of 3 g. of 4-(15-carbomethoxypentadecylamino)benzonitrile and 0.5 g. of potassium hydroxide in 50 ml. of 95% ethanol is stirred at 50° C. for 10 hours, diluted with water and acidified with dilute hydrochloric acid. The precipitate is collected, dried and recrystallized from ether-hexane to yield 4-(15-carboxypentadecylamino)benzonitrile as a white solid.
Reaction SMILES: [CH3:1][C@@H:2]1[C@H:6]([OH:7])[C@@H:5]([CH2:8][OH:9])[O:4][C@H:3]1[N:10]1[CH:17]=[CH:16][C:14](=[O:15])[NH:13][C:11]1=[S:12].[CH3:18][O:19][C:20]1[CH:41]=[CH:40][C:23]([C:24](Cl)([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[C:25]2[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][CH:26]=2)=[CH:22][CH:21]=1>N1C=CC=CC=1.CN(C)C1C=CN=CC=1>[CH3:32][O:31][C:28]1[CH:27]=[CH:26][C:25]([C:24]([O:9][CH2:8][C@H:5]2[O:4][C@@H:3]([N:10]3[CH:17]=[CH:16][C:14](=[O:15])[NH:13][C:11]3=[S:12])[C@H:2]([CH3:1])[C@@H:6]2[OH:7])([C:33]2[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=2)[C:23]2[CH:40]=[CH:41][C:20]([O:19][CH3:18])=[CH:21][CH:22]=2)=[CH:30][CH:29]=1
Reactant: C[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1n1ccc(=O)[nH]c1=S
Reactant: COc1ccc(C(Cl)(c2ccccc2)c2ccc(OC)cc2)cc1
Agent: CN(C)c1ccncc1
Solvent: c1ccncc1
Product: COc1ccc(C(OC[C@H]2O[C@@H](n3ccc(=O)[nH]c3=S)[C@H](C)[C@@H]2O)(c2ccccc2)c2ccc(OC)cc2)cc1
Reaction time: 12 h

Procedure:
To a stirred solution of 2′-deoxy-2′-methylthiouridine (1.09 g, 4 mmol) in dry pyridine (10 mL) was added 4,4′-dimethoxytritylchloride (1.69 g, 5 mmol) and 4-dimethylaminopyridine (50 mg) at room temperature. The solution was stirred for 12 hours and the reaction mixture quenched by adding MeOH (1 mL). The reaction mixture was concentrated under reduced pressure and the residue was dissolved in CH2Cl2 (100 mL), washed with saturated aqueous NaHCO3 (2×50 mL) and saturated aqueous NaCl (2×50 mL), and dried with MgSO4. The solution was concentrated under reduced pressure and the residue purified by silica gel (30 g) column chromatography. Elution with CH2Cl2—MeOH-triethylamine (89:1:1) furnished the title compound as a homogenous material. Pooling and concentrating the appropriate fractions furnished the 5′-O—DMT nucleoside as a foam (1.5 g, 66.5%).
Reaction SMILES: [F:1][CH:2]([F:22])[C:3]1[N:8]=[C:7]([C:9]([F:12])([F:11])[F:10])[C:6]([C:13](=[O:16])[S:14][CH3:15])=[C:5]([NH2:17])[C:4]=1[C:18](=[O:21])SC.C(O)C.[OH-:26].[Na+]>C(OCC)(=O)C>[NH2:17][C:5]1[C:4]([C:18]([OH:21])=[O:26])=[C:3]([CH:2]([F:1])[F:22])[N:8]=[C:7]([C:9]([F:12])([F:10])[F:11])[C:6]=1[C:13]([S:14][CH3:15])=[O:16]
Reactant: [OH-]
Reactant: CSC(=O)c1c(C(F)F)nc(C(F)(F)F)c(C(=O)SC)c1N
Agent: [Na+]
Solvent: CCO
Solvent: CCOC(C)=O
Product: CSC(=O)c1c(C(F)(F)F)nc(C(F)F)c(C(=O)O)c1N
Reaction time: 24 h

Procedure:
A solution of 40.8 g (0.113 mol) of product of Example 191, 400 ml of ethanol and 4.5 g (0.113 mol) of 10% aqueous sodium hydroxide was stirred at 25° C. for 5 days. Another 2 g (0.05 mol) of sodium hydroxide was added and stirring continued for 24 hours. The reaction mixture was then diluted with ethyl acetate and washed with three 500 ml portions of 5% HCl, dried (CaSO4), filtered and concentrated to 31.4 g (84%) of product as a yellow solid; mp 219° C. (dec).
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:7]=[C:8]([C:12]2[C:16]3[S:17][CH:18]=[CH:19][C:15]=3[O:14][N:13]=2)[CH:9]=[CH:10][CH:11]=1.C(=O)([O-])[O-].[K+].[K+].[CH3:26][O:27][C:28]1[CH:29]=[C:30]([CH:33]=[CH:34][CH:35]=1)[CH2:31][NH2:32]>C(#N)C>[CH3:26][O:27][C:28]1[CH:29]=[C:30]([CH:33]=[CH:34][CH:35]=1)[CH2:31][NH:32][CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([C:12]2[C:16]3[S:17][CH:18]=[CH:19][C:15]=3[O:14][N:13]=2)[CH:7]=1
Reactant: BrCCCOc1cccc(-c2noc3ccsc23)c1
Reactant: COc1cccc(CN)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: COc1cccc(CNCCCOc2cccc(-c3noc4ccsc34)c2)c1

Procedure:
The title compound is prepared from 3-[3-(3-bromo-propoxy)-phenyl]-thieno[2,3-d]isoxazole, potassium carbonate, 3-methoxybenzylamine and acetonitrile essentially as described above in example 48. Purity by LC/MS (APCI)=93%, [M+H]+=395.
Reaction SMILES: C1(C)C=CC(S([CH2:10][N+:11]#[C-:12])(=O)=O)=CC=1.[C:14]([O:20][CH3:21])(=[O:19])[CH:15]=[CH:16][CH2:17][CH3:18].CC(C)([O-])C.[K+]>>[CH2:17]([C:16]1[C:15]([C:14]([O:20][CH3:21])=[O:19])=[CH:10][NH:11][CH:12]=1)[CH3:18]
Reactant: CCC=CC(=O)OC
Reactant: [C-]#[N+]CS(=O)(=O)c1ccc(C)cc1
Agent: CC(C)(C)[O-]
Agent: [K+]
Product: CCc1c[nH]cc1C(=O)OC
Yield: 63.7 %

Procedure:
Using p-toluenesulfonylmethyl isocyanide (10.1 g), methyl 2-pentenoate (6.01 g) and potassium tert-butoxide (7.01 g), a procedure as in Reference Example 39 was performed to give the title compound as pale-yellow crystals (yield 5.05 g, 64%).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:31])[CH2:4][O:5][C:6]1[CH:15]=[CH:14][C:13]([F:16])=[C:12]2[C:7]=1[C:8]([O:27][CH:28]([F:30])[F:29])=[C:9]([CH2:19][C:20]1[CH:25]=[CH:24][C:23](Br)=[CH:22][CH:21]=1)[C:10]([CH2:17][CH3:18])=[N:11]2.C([Sn](CCCC)(CCCC)[C:37]1[O:38][CH:39]=[CH:40][N:41]=1)CCC.O1CCOCC1>C(OCC)(=O)C.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>[CH3:1][O:2][C:3](=[O:31])[CH2:4][O:5][C:6]1[CH:15]=[CH:14][C:13]([F:16])=[C:12]2[C:7]=1[C:8]([O:27][CH:28]([F:30])[F:29])=[C:9]([CH2:19][C:20]1[CH:25]=[CH:24][C:23]([C:37]3[O:38][CH:39]=[CH:40][N:41]=3)=[CH:22][CH:21]=1)[C:10]([CH2:17][CH3:18])=[N:11]2
Reactant: CCc1nc2c(F)ccc(OCC(=O)OC)c2c(OC(F)F)c1Cc1ccc(Br)cc1
Reactant: CCCC[Sn](CCCC)(CCCC)c1ncco1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: C1COCCO1
Solvent: CCOC(C)=O
Product: CCc1nc2c(F)ccc(OCC(=O)OC)c2c(OC(F)F)c1Cc1ccc(-c2ncco2)cc1
Temperature: 100 °C

Procedure:
A mixture of [3-(4-bromobenzyl)-4-difluoromethoxy-2-ethyl-8-fluoroquinolin-5-yloxy]acetic acid methyl ester (0.36 g), 2-tributylstannanyloxazole (0.46 mL), tetrakis(triphenylphosphine)palladium(0) (0.084 g) and 1,4-dioxane (3.0 mL) was heated at 100° C. for 3 hours. The mixture was cooled to room temperature, diluted with ethyl acetate, washed with water, and then dried over magnesium sulfate. The solvent was removed under reduced pressure to afford title compound as a yellow gum (1.1 g).
Reaction SMILES: O[CH2:2][C:3]1[C:4]([N:18]2[CH2:27][CH2:26][C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[CH:19]2[CH3:28])=[N:5][C:6]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=2)=[N:7][C:8]=1[CH3:9].C(N(S(F)(F)[F:35])CC)C.[Cl:38]CCl>>[ClH:38].[F:35][CH2:2][C:3]1[C:4]([N:18]2[CH2:27][CH2:26][C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[CH:19]2[CH3:28])=[N:5][C:6]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=2)=[N:7][C:8]=1[CH3:9]
Reactant: ClCCl
Reactant: Cc1nc(Nc2ccc(F)cc2)nc(N2CCc3ccccc3C2C)c1CO
Reactant: CCN(CC)S(F)(F)F
Product: Cc1nc(Nc2ccc(F)cc2)nc(N2CCc3ccccc3C2C)c1CF
Product: Cl
Yield: 14 %

Procedure:
The same procedures as in Example 24 above were repeated using 5-hydroxymethyl-6-methyl-2-(4-fluorophenylamino)-4-(1-methyl-1,2,3,4-tetrahydroisoquinolin-2-yl)pyrimidine (0.19 g, 0.5mmol) prepared in accordance with WO 98/43968, dichloromethane (5 ml), and (diethylamino)sulfur trifluoride (0.15 ml, 2.26 mmol) to afford 27 mg (14%) of the titled compound.
Reaction SMILES: Cl.Cl.Cl.[O:4]1[C:8]2=[C:9]([N:13]3[CH2:18][CH2:17][N:16]([CH2:19][CH2:20][C@H:21]4[CH2:26][CH2:25][C@H:24]([NH2:27])[CH2:23][CH2:22]4)[CH2:15][CH2:14]3)[N:10]=[CH:11][CH:12]=[C:7]2[CH2:6][CH2:5]1.[CH3:28][C:29]1[O:33][N:32]=[C:31]([C:34]2[CH:35]=[C:36]([CH:40]=[CH:41][CH:42]=2)[C:37](O)=[O:38])[N:30]=1>>[O:4]1[C:8]2=[C:9]([N:13]3[CH2:18][CH2:17][N:16]([CH2:19][CH2:20][C@H:21]4[CH2:26][CH2:25][C@H:24]([NH:27][C:37](=[O:38])[C:36]5[CH:40]=[CH:41][CH:42]=[C:34]([C:31]6[N:30]=[C:29]([CH3:28])[O:33][N:32]=6)[CH:35]=5)[CH2:23][CH2:22]4)[CH2:15][CH2:14]3)[N:10]=[CH:11][CH:12]=[C:7]2[CH2:6][CH2:5]1
Reactant: Cc1nc(-c2cccc(C(=O)O)c2)no1
Reactant: N[C@H]1CC[C@H](CCN2CCN(c3nccc4c3OCC4)CC2)CC1
Agent: Cl
Product: Cc1nc(-c2cccc(C(=O)N[C@H]3CC[C@H](CCN4CCN(c5nccc6c5OCC6)CC4)CC3)c2)no1

Procedure:
The title compound, white solid (120 mg, 93%), MS (ISP) m/z=517.5 [(M+H)+], mp 227.5° C., was prepared in accordance with the general method of example 6 from trans-4-{2-[4-(2,3-dihydro-furo[2,3-c]pyridin-7-yl)-piperazin-1-yl]-ethyl}-cyclohexylamine trihydrochloride (intermediate B) (110 mg, 0.25 mmol) and 3-(5-methyl-[1,2,4]oxadiazol-3-yl)-benzoic acid.
Reaction SMILES: C(OC([O:7][C@@H:8]([C@H:10]1[C:25](=[O:26])[N:12]2[C:13]([C:19]([O:21]CC=C)=[O:20])=[C:14]([CH2:17]O)[C@H:15]([CH3:16])[C@H:11]12)[CH3:9])=O)C=C.[C:27]([C:30]1[N:31]2[CH:37]=[N:36][CH:35]=[C:32]2[S:33][CH:34]=1)(=[O:29])[NH2:28]>>[OH:7][C@@H:8]([C@H:10]1[C:25](=[O:26])[N:12]2[C:13]([C:19]([O-:21])=[O:20])=[C:14]([CH2:17][N:36]3[CH:35]=[C:32]4[S:33][CH:34]=[C:30]([C:27](=[O:29])[NH2:28])[N+:31]4=[CH:37]3)[C@H:15]([CH3:16])[C@H:11]12)[CH3:9]
Reactant: NC(=O)c1csc2cncn12
Reactant: C=CCOC(=O)O[C@H](C)[C@H]1C(=O)N2C(C(=O)OCC=C)=C(CO)[C@H](C)[C@H]12
Product: C[C@@H](O)[C@H]1C(=O)N2C(C(=O)[O-])=C(Cn3cc4scc(C(N)=O)[n+]4c3)[C@H](C)[C@H]12
Yield: 8 %

Procedure:
The same procedure as in Example 1 was repeated except that 113 mg of allyl (1S,5R,6S)-6-[(1R)-1-allyloxycarbonyloxyethyl]-2-hydroxymethyl-1-methyl-1-carbapen-2-em-3-carboxylate and 260 mg of 3-carbamoylimidazo[5,1-b]thiazole were used, thereby obtaining 9.6 mg of the title compound.