Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [I-].C[S+](C)(C)=O.[CH3:7]C(C)([O-])C.[K+].O1CCCC1.[CH:18]([CH:20]([NH:42][C:43](=[O:49])[O:44][C:45]([CH3:48])([CH3:47])[CH3:46])[CH2:21][CH:22]([CH2:26][C:27]1[CH:36]=[CH:35][C:34]2[C:29](=[C:30]([O:37][CH2:38][CH2:39][O:40][CH3:41])[CH:31]=[CH:32][CH:33]=2)[CH:28]=1)[CH:23]([CH3:25])[CH3:24])=[O:19]>CS(C)=O>[CH3:41][O:40][CH2:39][CH2:38][O:37][C:30]1[CH:31]=[CH:32][CH:33]=[C:34]2[C:29]=1[CH:28]=[C:27]([CH2:26][CH:22]([CH:23]([CH3:25])[CH3:24])[CH2:21][CH:20]([NH:42][C:43](=[O:49])[O:44][C:45]([CH3:47])([CH3:46])[CH3:48])[CH:18]1[CH2:7][O:19]1)[CH:36]=[CH:35]2
Reactant: COCCOc1cccc2ccc(CC(CC(C=O)NC(=O)OC(C)(C)C)C(C)C)cc12
Reactant: CC(C)(C)[O-]
Agent: C[S+](C)(C)=O
Agent: [I-]
Agent: [K+]
Solvent: C1CCOC1
Solvent: CS(C)=O
Product: COCCOc1cccc2ccc(CC(CC(NC(=O)OC(C)(C)C)C3CO3)C(C)C)cc12
Temperature: 0 °C

Procedure:
3.87 g of trimethylsulphoxonium iodide and 1.98 g of potassium tert-butoxide are stirred under high vacuum overnight, admixed with 24 ml of tetrahydrofuran and subsequently cooled to 0° C. A solution of 3.03 g of tert-butyl {1-formyl-3-[8-(2-methoxyethoxy)naphthalen-2-ylmethyl]-4-methylpentyl}carbamate in 24 ml of dimethyl sulphoxide is added dropwise. On completion of reaction (TLC monitoring), the reaction mixture is partitioned between water and tert-butyl methyl ether, and the aqueous phase is extracted once again with tert-butyl methyl ether (2×). The combined organic phases are washed successively with water (3×) and brine, dried over sodium sulphate and concentrated by evaporation. The title compound is identified on the basis of the Rf value from the residue by means of flash chromatography (SiO2 60F).
Reaction SMILES: [Cl:1][C:2]1[CH:17]=[CH:16][C:5]([C:6]([C:8]2[CH:15]=[CH:14][C:11]([CH2:12]Br)=[CH:10][CH:9]=2)=[O:7])=[CH:4][CH:3]=1.[N-:18]=[N+:19]=[N-:20].[Na+]>C(O)C>[Cl:1][C:2]1[CH:17]=[CH:16][C:5]([C:6]([C:8]2[CH:15]=[CH:14][C:11]([CH2:12][N:18]=[N+:19]=[N-:20])=[CH:10][CH:9]=2)=[O:7])=[CH:4][CH:3]=1
Reactant: [N-]=[N+]=[N-]
Reactant: O=C(c1ccc(Cl)cc1)c1ccc(CBr)cc1
Agent: [Na+]
Solvent: CCO
Product: [N-]=[N+]=NCc1ccc(C(=O)c2ccc(Cl)cc2)cc1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
A mixture of 4-(4-chlorobenzoyl)benzyl bromide (4.36 g, 14.1 mmol) and sodium azide (1.32 g, 20.3 mmol) in ethanol (40 ml) was refluxed 5 hours, cooled to ambient temperature, and stirred 16 hours. The mixture was filtered and the solids were washed twice with ethanol and once with diethyl ether. The combined filtrate and washes were evaporated under vacuum to provide 3.63 (95%) of 4-(4-chlorobenzoyl)benzyl azide, m.p. 71°-73° C.
Reaction SMILES: [NH2:1][C:2]1[N:6]([CH2:7][CH2:8][CH3:9])[N:5]=[CH:4][C:3]=1[C:10]#[N:11].[C:12]1([C:18](Cl)([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1>N1C=CC=CC=1>[CH2:7]([N:6]1[C:2]([NH:1][C:18]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)([C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=2)[C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)=[C:3]([C:10]#[N:11])[CH:4]=[N:5]1)[CH2:8][CH3:9]
Reactant: CCCn1ncc(C#N)c1N
Reactant: ClC(c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: c1ccncc1
Product: CCCn1ncc(C#N)c1NC(c1ccccc1)(c1ccccc1)c1ccccc1
Temperature: 60 °C
Reaction time: 5 h
Yield: 87.2 %

Procedure:
To a suspension of 5-amino-1-propyl-1H-pyrazole-4-carbonitrile (16.32 g) in pyridine (160 ml) was added triphenylmethyl chloride (36.35 g) at room temperature. After stirring at 60° C. for 5 hours, the reaction mixture was evaporated in vacuo. The residue was added to a mixture of tetrahydrofuran and brine, and the organic layer was separated and washed with brine. The extract was dried over anhydrous magnesium sulfate, filtered, and evaporated in vacuo. To the residue was triturated with diisopropyl ether to give 1-propyl-5-tritylamino-1H-pyrazole-4-carbonitrile (37.21 g) as a colorless solid.
Reaction SMILES: [CH3:1][C:2]1[S:6][C:5]([C:7]([O:9][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[O:8])=[CH:4][CH:3]=1.[Br:17]N1C(=O)CCC1=O>N(C(C)(C)C#N)=NC(C)(C)C#N.C(Cl)(Cl)(Cl)Cl>[Br:17][CH2:1][C:2]1[S:6][C:5]([C:7]([O:9][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[O:8])=[CH:4][CH:3]=1
Reactant: Cc1ccc(C(=O)OCc2ccccc2)s1
Reactant: O=C1CCC(=O)N1Br
Agent: CC(C)(C#N)N=NC(C)(C)C#N
Solvent: ClC(Cl)(Cl)Cl
Product: O=C(OCc1ccccc1)c1ccc(CBr)s1
Temperature: 80 °C
Reaction time: 8 h
Yield: 62.9 %

Procedure:
To a mixture of 5.27 g of benzyl 5-methylthiophene-2-carboxylate and 100 mL of carbon tetrachloride were added 4.18 g of N-bromosuccinimide (NBS) and 142 mg of azobisisobutyronitrile (AIBN), followed by stirring overnight at 80° C. The reaction mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (hexane:ethyl acetate=7:3), thereby obtaining 4.44 g of benzyl 5-(bromomethyl)thiophene-2-carboxylate.
Reaction SMILES: [C:1]([O:5][C:6]([C@@:8]1([CH2:25]C=C)[C@@H:12]([CH2:13][CH:14]=[CH2:15])[C:11](=[O:16])[N:10]([C@@H:17]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH3:18])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]>Cl[Ru](=C1N(C2C(C)=CC(C)=CC=2C)CCN1C1C(C)=CC(C)=CC=1C)(Cl)(=CC1C=CC=CC=1)[P](C1CCCCC1)(C1CCCCC1)C1CCCCC1.ClCCl>[C:1]([O:5][C:6]([C@:8]12[CH2:9][N:10]([C@@H:17]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[CH3:18])[C:11](=[O:16])[C@@H:12]1[CH2:13][CH:14]=[CH:15][CH2:25]2)=[O:7])([CH3:3])([CH3:2])[CH3:4]
Reactant: C=CC[C@H]1C(=O)N([C@H](C)c2ccccc2)C[C@@]1(CC=C)C(=O)OC(C)(C)C
Agent: Cc1cc(C)c(N2CCN(c3c(C)cc(C)cc3C)C2=[Ru](Cl)(Cl)(=Cc2ccccc2)[P](C2CCCCC2)(C2CCCCC2)C2CCCCC2)c(C)c1
Solvent: ClCCl
Product: C[C@H](c1ccccc1)N1C[C@]2(C(=O)OC(C)(C)C)CC=CC[C@H]2C1=O
Temperature: 25 °C
Reaction time: 1 h
Yield: 87.2 %

Procedure:
The Second Generation Grubbs' catalyst (91.9 mg, 0.108 mmol) was added to a solution of (3S,4R)-3,4-diallyl-5-oxo-1-[(1R)-1-phenylethyl]pyrrolidine-3-carboxylic acid tert-butyl ester (2.00 g, 5.41 mmol) in dichloromethane (54.1 mL) in a nitrogen atmosphere, and the mixture was stirred at room temperature for one hour. The reaction solution was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=100:0→90:10→80:20→75:25→66:34→50:50) to give 1.61 g of the title compound.
Reaction SMILES: [Zn]([CH2:4][CH3:5])CC.ClCI.[C:9]([O:13][C:14]([N:16]1[CH2:21][CH2:20][C:19](=[CH2:22])[CH:18](O)C1)=[O:15])([CH3:12])([CH3:11])[CH3:10]>ClCCCl>[C:9]([O:13][C:14]([N:16]1[CH2:5][CH2:4][C:19]2([CH2:18][CH2:22]2)[CH2:20][CH2:21]1)=[O:15])([CH3:10])([CH3:11])[CH3:12]
Reactant: CC[Zn]CC
Reactant: C=C1CCN(C(=O)OC(C)(C)C)CC1O
Agent: ClCI
Solvent: ClCCCl
Product: CC(C)(C)OC(=O)N1CCC2(CC1)CC2
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 56791.1 %

Procedure:
To a solution of Et2Zn (37.5 ml, 1.1M solution in toluene, 0.04 mmol) in DCE (80 ml) at 0° C. was added chloroiodomethane (5.99 ml, 0.08 mmol) under Ar. This mixture was stirred for 15 minutes before a solution of 3-hydroxy-4-methylene-piperidine-1-carboxylic acid tert-butyl ester (J. Org. Chem. 2001, 66, 2487) (4.19 g, 0.02 mmol) in DCE (10 ml) was added, after which time the reaction was stirred for 0.5 h at 0° C. and then allowed to reach room temperature, stirring for a further 1 h. The reaction was then quenched by addition of saturated NH4Cl, separated, and the organic dried (Na2SO4) and concentrated. Purfication by flash column chromatography (EtOAc:n-heptane 2:8-1:1) afforded the title product (2.4 g, 54%) as a crystalline solid. MS: 228.2 (MH+).
Reaction SMILES: [CH2:1]([O:3][C:4]([C@@H:6]([NH:15][C@H:16]([C:18]([N:20]1[CH2:27][CH2:26][CH2:25][C@H:21]1[C:22]([OH:24])=[O:23])=[O:19])[CH3:17])[CH2:7][CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)=[O:5])[CH3:2].[ClH:28].[CH2:29](O)[CH3:30]>>[ClH:28].[CH2:1]([O:3][C:4]([C@@H:6]([NH:15][C@H:16]([C:18]([N:20]1[CH2:27][CH2:26][CH2:25][C@H:21]1[C:22]([O:24][CH2:29][CH3:30])=[O:23])=[O:19])[CH3:17])[CH2:7][CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)=[O:5])[CH3:2]
Reactant: CCO
Reactant: CCOC(=O)[C@H](CCc1ccccc1)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)O
Agent: Cl
Product: CCOC(=O)[C@H](CCc1ccccc1)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)OCC
Reaction time: 8 h

Procedure:
A solution of 3.0 g of N-[1-(S)-ethoxycarbonyl-3-phenylpropyl]-L-alanyl-L-proline in 50 ml of absolute ethanol is saturated with HCl gas at 0°. After standing at 0° overnight, the HCl and ethanol are removed under vacuum to afford 3.1 g of an oil which upon freeze-drying gives a white solid. Thin layer chromatography and HPLC indicate only one component. The nmr spectrum indicates two ethyl groups per aromatic ring. The mass spectrum shows a molecular ion at 404 m/e.
Reaction SMILES: [Cl:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([C:12]([F:15])([F:14])[F:13])=[CH:9][CH:10]=2)[N:5]=[CH:4][CH:3]=1.ClC1C=CC=C(C(OO)=[O:24])C=1.C(=O)([O-])O.[Na+]>C(Cl)(Cl)Cl>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([C:12]([F:15])([F:13])[F:14])=[CH:9][CH:10]=2)[N+:5]([O-:24])=[CH:4][CH:3]=1
Reactant: FC(F)(F)c1ccc2c(Cl)ccnc2c1
Reactant: O=C(OO)c1cccc(Cl)c1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClC(Cl)Cl
Product: [O-][n+]1ccc(Cl)c2ccc(C(F)(F)F)cc21
Temperature: 25 °C
Reaction time: 3.5 h

Procedure:
To 14 mL of a chloroform solution containing 0.90 g of 4-chloro-7-trifluoromethylquinoline, 1.04 g of m-chloroperbenzoic acid was added, and the mixture was stirred at room temperature for 3.5 hours. The reaction mixture was added with 15 mL of an aqueous saturated sodium hydrogen carbonate solution. The organic layer was separated, and the aqueous layer was extracted with chloroform. The organic layer and the extract were combined, the resultant solution was washed with an aqueous saturated sodium chloride solution, and dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure to obtain a yellow solid, 4-chloro-7-trifluoromethylquinoline N-oxide.
Reaction SMILES: CCCC[N+](CCCC)(CCCC)CCCC.[F-].C([Si](C)(C)[O:24][CH2:25][CH2:26][O:27][CH:28]1[CH2:33][O:32][CH:31]([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[O:30][CH2:29]1)(C)(C)C.[Cl-].[NH4+]>C1COCC1>[C:34]1([CH:31]2[O:32][CH2:33][CH:28]([O:27][CH2:26][CH2:25][OH:24])[CH2:29][O:30]2)[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=1
Reactant: CC(C)(C)[Si](C)(C)OCCOC1COC(c2ccccc2)OC1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [Cl-]
Agent: [F-]
Solvent: C1CCOC1
Product: OCCOC1COC(c2ccccc2)OC1
Temperature: 25 °C
Reaction time: 16 h
Yield: 17.2 %

Procedure:
A solution of TBAF in 1 M-THF (1 mL, 1.00 mmol) was added to 5 mL of a solution of crude tert-butyldimethyl-[2-(2-phenyl-[1,3]dioxan-5-yloxy)ethoxy]silane (343 mg, 1.01 mmol) obtained in Step A in THF, and the mixture was stirred at room temperature for 16 hours. Aqueous saturated ammonium chloride was added to the mixture, followed by extraction with ethyl acetate. The extract was washed with saturated saline and then dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The resulting residue was purified by silica gel column chromatography (methylene chloride:methanol=50:1) to obtain 2-(2-phenyl-[1,3]dioxan-5-yloxy)ethanol (39 mg, yield: 17%) as a colorless oil.
Reaction SMILES: [I-].C[S+](C)C.[H-].[Na+].[F:8][C:9]([F:19])([F:18])[C:10]1[CH:17]=[CH:16][C:13]([CH:14]=[CH2:15])=[CH:12][CH:11]=1.[OH2:20]>CS(C)=O>[F:8][C:9]([F:18])([F:19])[C:10]1[CH:17]=[CH:16][C:13]([CH:14]2[CH2:15][O:20]2)=[CH:12][CH:11]=1
Reactant: O
Reactant: C=Cc1ccc(C(F)(F)F)cc1
Agent: C[S+](C)C
Agent: [H-]
Agent: [I-]
Solvent: CS(C)=O
Product: FC(F)(F)c1ccc(C2CO2)cc1
Yield: 81 %

Procedure:
Trimethylsulfonium iodide (4.08 g, 20.0 mmol) in dimethyl sulfoxide (15 mL) was stirred with sodium hydride (55 wt % dispersion in mineral oil, 873 mg, 20.0 mmol) at room temperature for 1 hour and then with 4-(trifluoromethyl)styrene (2.96 g, 17.0 mmol) in dimethyl sulfoxide (10 mL) at room temperature for 2 hours. After addition of water, the reaction mixture was extracted with ethyl acetate, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=9/1 (v/v)) to give the title compound as a colorless oil (2.59 g, yield 81%).
Reaction SMILES: CN1C([NH:7][CH2:8][CH2:9][CH2:10][O:11][C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([CH2:18][N:19]3[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]3)[CH:13]=2)=NC(CCC(O)=O)=N1.[CH3:30][N:31]([C:40](=[N:43][C:44](=[O:51])[CH2:45][C:46]([O:48][CH2:49][CH3:50])=[O:47])SC)[N:32]=[CH:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1>>[CH3:30][N:31]([C:40](=[N:43][C:44](=[O:51])[CH2:45][C:46]([O:48][CH2:49][CH3:50])=[O:47])[NH:7][CH2:8][CH2:9][CH2:10][O:11][C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([CH2:18][N:19]2[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]2)[CH:13]=1)[N:32]=[CH:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1
Reactant: Cn1nc(CCC(=O)O)nc1NCCCOc1cccc(CN2CCCCC2)c1
Reactant: CCOC(=O)CC(=O)N=C(SC)N(C)N=Cc1ccccc1
Product: CCOC(=O)CC(=O)N=C(NCCCOc1cccc(CN2CCCCC2)c1)N(C)N=Cc1ccccc1
Yield: 155.6 %

Procedure:
A mixture of 3-[3-(1-piperidinylmethyl)phenoxy]propanamine (A) (3.61 g) and ethyl 3-[[[1-methyl-2-(phenylmethylene)hydrazino](methylthio)methylene]amino]-3-oxopropanoate (4.7 g) was heated at 50° under water pump vacuum during 4 h. to gave the title compound as an orange gum (7.3 g). T.l.c. System D, Rf 0.65.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([CH:12]=[C:13]([Cl:15])[CH:14]=1)[O:5][C:6]1[CH:7]=[N:8][CH:9]=[CH:10][CH:11]=1.[Cl:16][C:17]1[CH:18]=[C:19]([CH:23]=[CH:24][CH:25]=1)[C:20]([NH2:22])=[O:21].CC([O-])(C)C.[Na+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2]>[Cl:16][C:17]1[CH:18]=[C:19]([CH:23]=[CH:24][CH:25]=1)[C:20]([NH:22][C:2]1[CH:3]=[C:4]([O:5][C:6]2[CH:7]=[N:8][CH:9]=[CH:10][CH:11]=2)[CH:12]=[C:13]([Cl:15])[CH:14]=1)=[O:21]
Reactant: NC(=O)c1cccc(Cl)c1
Reactant: Clc1cc(Br)cc(Oc2cccnc2)c1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: CC(C)(C)[O-]
Solvent: Cc1ccccc1
Product: O=C(Nc1cc(Cl)cc(Oc2cccnc2)c1)c1cccc(Cl)c1
Temperature: 110 °C
Yield: 73.3 %

Procedure:
Compound 11 (1.0 g, 3.5 mmol, 1.0 eq), 3-chlorobenzamide (820 mg, 5.27 mmol, 1.50 eq), NaOt-Bu (473 mg, 4.92 mmol, 1.40 eq), Pd(OAc)2 (40 mg, 0.18 mmol, 0.050 eq) and Xantphos (203 mg, 0.351 mmol, 0.100 eq) were dissolved in toluene (15 mL) in a microwave vial. The vial was purged with argon, capped, and heated at 110° C. for 18 h. After cooling the reaction was filtered over a plug of celite and the plug was washed with 5% MeOH/CH2Cl2. The solvents were removed in vacuo and the crude mixture was purified by flash chromatography on silica gel afforded 921 mg (73%) of the title compound as a white solid: 1H NMR (400 MHz, CDCl3) δ 10.5 (s, 1H), 8.47 (d, J=2.8 Hz, 1H), 8.45 (dd, J=4.6, 1.3 Hz, 1H), 7.95 (t, J=1.8 Hz, 1H), 7.86 (dt, J=7.8, 1.3 Hz, 1H), 7.77 (t, J=1.8 Hz, 1H), 7.67 (dq, J=8.1, 1.2 Hz, 1H), 7.58 (ddd, J=8.4, 2.9, 1.4 Hz, 1H), 7.56 (t, J=7.9 Hz, 1H), 7.49 (dd, J=8.4, 4.7, 1H), 7.40 (t, J=2.1 Hz, 1H), 6.94 (t, J=2.1 Hz, 1H); [M+1]+: 359.2.
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[C:13]3[CH:20]=[CH:19][CH:18]=[CH:17][C:14]=3[S:15][CH:16]=2)=[CH:8][CH:7]=1.[Cl:21][C:22]1[CH:29]=[CH:28][CH:27]=[CH:26][C:23]=1[CH2:24][NH2:25].C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[S:15]1[CH:16]=[C:12]([C:9]2[CH:10]=[CH:11][C:6]([O:5][CH2:4][CH2:3][CH2:2][NH:25][CH2:24][C:23]3[CH:26]=[CH:27][CH:28]=[CH:29][C:22]=3[Cl:21])=[CH:7][CH:8]=2)[C:13]2[CH:20]=[CH:19][CH:18]=[CH:17][C:14]1=2
Reactant: BrCCCOc1ccc(-c2csc3ccccc23)cc1
Reactant: NCc1ccccc1Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: Clc1ccccc1CNCCCOc1ccc(-c2csc3ccccc23)cc1
Yield: 78.3 %

Procedure:
Combine 3-[4-(3-bromo-propoxy)-phenyl]-benzo[b]thiophene (0.200 g, 0.576 mmol), 2-chlorobenzylamine (0.326 g, 2.30 mmol), potassium carbonate (0.200 g, 1.45 mmol) and acetonitrile (4.0 ml) and heat (75° C.) overnight. Cool reaction to room temperature, filter through a Waters Sep-Pak 1 g Silica cartridge (ethyl acetate) and concentrate (in vacuo). Purify the crude product by column (silica) chromatography with a graded solvent mixture of 40% ethyl acetate in dichloromethane to 100% ethyl acetate. Concentrate the appropriate fractions, dissolve in dichloromethane and re-evaporate under a stream of nitrogen. Dry sample under vacuum (0.5 mm Hg, 50° C.) overnight to obtain the title compound as a light amber oil (0.184 g, 78% Yield). Purity by LC/MS=98%, [M+H]+=408.
Reaction SMILES: NC1C(C(NC)=O)=NC(C2C(C)=NN(CCCO)C=2)=CC=1.[NH2:22][C:23]1[C:24]([C:46]([NH:48][CH3:49])=[O:47])=[N:25][C:26]([C:29]2[CH:30]=[N:31][N:32]([CH2:35][CH2:36][CH2:37][O:38]CC3C=CC=CC=3)[C:33]=2[CH3:34])=[CH:27][CH:28]=1>>[NH2:22][C:23]1[C:24]([C:46]([NH:48][CH3:49])=[O:47])=[N:25][C:26]([C:29]2[CH:30]=[N:31][N:32]([CH2:35][CH2:36][CH2:37][OH:38])[C:33]=2[CH3:34])=[CH:27][CH:28]=1
Reactant: CNC(=O)c1nc(-c2cnn(CCCOCc3ccccc3)c2C)ccc1N
Agent: CNC(=O)c1nc(-c2cn(CCCO)nc2C)ccc1N
Product: CNC(=O)c1nc(-c2cnn(CCCO)c2C)ccc1N
Yield: 54.1 %

Procedure:
Prepared analogously to Compound 34C replacing Compound 34D with 3-amino-6-{1-[3-(benzyloxy)propyl]-5-methyl-1H-pyrazol-4-yl}-N-methylpyridine-2-carboxamide (Compound 34E, 429 mg, 1.13 mmol) to afford 177 mg of the title compound (54%). 1H NMR (400 MHz, CD3OD) δ 7.75 (s, 1H), 7.35 (d, J=8.8 Hz, 1H), 7.12 (d, J=8.6 Hz, 1H), 4.18 (t, J=7.1 Hz, 2H), 3.51 (t, J=6.2 Hz, 2H), 2.89 (s, 3H), 2.51 (s, 3H), 1.97 (quin, J=6.6 Hz, 2H). MS (ESI): m/z=290.57 [M+H]+. UPLC: tR=0.67 min (UPLC-SQD: analytical—2 min).
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([N+:8]([O-])=O)[C:5]([F:11])=[CH:4][C:3]=1[CH2:12][C:13]([OH:15])=[O:14].CC(O)=O>CCOC(C)=O.[Pd]>[NH2:8][C:6]1[C:5]([F:11])=[CH:4][C:3]([CH2:12][C:13]([OH:15])=[O:14])=[C:2]([F:1])[CH:7]=1
Reactant: O=C(O)Cc1cc(F)c([N+](=O)[O-])cc1F
Agent: [Pd]
Solvent: CC(=O)O
Solvent: CCOC(C)=O
Product: Nc1cc(F)c(CC(=O)O)cc1F
Temperature: 25 °C
Reaction time: 3 h

Procedure:
To a solution of (2,5-difluoro-4-nitrophenyl)acetic acid (440 mg, 2.03 mmol) in 20 ml of EtOAc was added HOAc (121 mg, 2.03 mmol) and 200 mg of Pd/C was stirred at room temperature under H2 atmosphere for 3 hours. The reaction mixture was filtrated and concentrated to give (4-amino-2,5-difluorophenyl)acetic acid.
Reaction SMILES: F[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][C:3]=1[Cl:11].[CH3:12][S-:13].[Na+]>CN(C=O)C.C(C1C(O)=CC(C)=C(SC2C=C(C(C)(C)C)C(O)=CC=2C)C=1)(C)(C)C>[Cl:11][C:3]1[CH:4]=[C:5]([N+:8]([O-:10])=[O:9])[CH:6]=[CH:7][C:2]=1[S:13][CH3:12]
Reactant: C[S-]
Reactant: O=[N+]([O-])c1ccc(F)c(Cl)c1
Agent: Cc1cc(O)c(C(C)(C)C)cc1Sc1cc(C(C)(C)C)c(O)cc1C
Agent: [Na+]
Solvent: CN(C)C=O
Product: CSc1ccc([N+](=O)[O-])cc1Cl
Reaction time: 6 h
Yield: 52.3 %

Procedure:
To a solution of 4-fluoro-3-chloronitrobenzene (27 g, 156 mmol) in DMF (150 mL) at room temperature was added 5-tert-butyl-4-hydroxy-2-methylphenyl sulfide (100 mg) followed by sodium thiomethoxide (NaSMe) (10 g, 143 mmol) and the reaction was stirred for 6 h. The DMF was removed in vacuo and the residue was partitioned between ether (1 L) and water (1 L). The ether layer was washed with water (1 L) and brine (1 L), dried (MgSO4) and the solvent was removed under reduced pressure. The residue was purified by column chromatography (SiO2; DCM: pentane 1:5 increasing polarity to 3:7) to give the title compound (15.22 g, 49%) as a yellow solid; δH (400 MHz, CDCl3) 2.53 (3H, s), 7.20 (1H, d), 8.09 (1H, dd), 8.20 (1H, d).
Reaction SMILES: [C:1]1([S:7][C@@H:8]2[O:16][C@H:15]([CH2:17][OH:18])[C@H:13]([OH:14])[C@H:11]([OH:12])[C@H:9]2[OH:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:19](Cl)(=[O:24])[C:20]([CH3:23])([CH3:22])[CH3:21]>N1C=CC=CC=1.CN(C1C=CN=CC=1)C>[C:1]1([S:7][C@@H:8]2[O:16][C@H:15]([CH2:17][O:18][C:19](=[O:24])[C:20]([CH3:23])([CH3:22])[CH3:21])[C@H:13]([O:14][C:19](=[O:24])[C:20]([CH3:23])([CH3:22])[CH3:21])[C@H:11]([O:12][C:19](=[O:24])[C:20]([CH3:23])([CH3:22])[CH3:21])[C@H:9]2[O:10][C:19](=[O:24])[C:20]([CH3:23])([CH3:22])[CH3:21])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: CC(C)(C)C(=O)Cl
Reactant: OC[C@H]1O[C@@H](Sc2ccccc2)[C@H](O)[C@@H](O)[C@H]1O
Agent: CN(C)c1ccncc1
Solvent: c1ccncc1
Product: CC(C)(C)C(=O)OC[C@H]1O[C@@H](Sc2ccccc2)[C@H](OC(=O)C(C)(C)C)[C@@H](OC(=O)C(C)(C)C)[C@H]1OC(=O)C(C)(C)C
Temperature: 95 °C
Reaction time: 8 h
Yield: 76.3 %

Procedure:
To a solution of 1-deoxy-1-(phenylthio)-β-D-galactopyranose (0.38 g, 1.4 mmol) in 25 mL of pyridine, pivaloyl chloride (1.75 mL, 14.0 mmol) and DMAP (0.200 g, 1.40 mmol) are added. The reaction mixture is stirred at 90-100° C. for 8 h. Pyridine is removed under reduced pressure, and the residue is dissolved in 100 mL of CH2Cl2 and washed with dilute HCl (100 mL), H2O (100 mL), dried over Na2SO4, filtered, concentrated and purified by flash chromatography (10% EtOAc/hexane) to give 0.65 g (76%) of 1-deoxy-1-(phenylthio)-2,3,4,6-tetra-O-pivaloyl-β-D-galactopyranose 40: Rf 0.59 (15% EtOAc/hexane); 1H NMR (CDCl3, 270 MHz) δ 7.97 (d, J=8.9 Hz, 2 H, ArH), 7.70 (t, J=7.3 Hz, 1 H, ArH), 7.60 (t, J=7.3 Hz, 2 H, ArH), 5.39 (t, J=9.9 Hz, 1 H, H-2), 5.30 (d, J=3.0 Hz, 1 H, H-4), 5.10 (dd, J=9.9, 3.0 Hz, 1 H, H-3), 4.57 (d, J=9.9 Hz, 1 H, H-1), 4.05-4.20 (m, 2 H, H-6), 3.79 (dd, J=10.6, 5.9 Hz, 1 H, H-5), 1.25-(s, 9 H), 1.18 (s, 9 H), 1.08 (s, 9H), 0.92 (s, 9 H). 13C NMR (CDCl3, 270 MHz) δ 177.7, 177.0, 176.7, 176.3, 134.4, 134.2, 131.0, 128.7, 89.4, 74.9, 71.7, 65.9, 63.9, 60.5, 38.4, 38.7, 38.6, 27.1.
Reaction SMILES: [NH:1]1[CH:8]=[N:7][C:5]([NH2:6])=[N:4][C:2]1=[O:3].C[Si](N[Si](C)(C)C)(C)C.C[Si](Cl)(C)C.[Si](OS(C(F)(F)F)(=O)=O)(C)(C)C.C(O[C@@H:39]1[O:51][C@H:50]([CH2:52][O:53]C(=O)C)[C@@H:45]([O:46]C(=O)C)[C@H:40]1[O:41]C(=O)C)(=O)C.C(=O)(O)[O-].[Na+].C[O-].[Na+].CO>C(#N)C>[C@@H:39]1([N:1]2[CH:8]=[N:7][C:5]([NH2:6])=[N:4][C:2]2=[O:3])[O:51][C@H:50]([CH2:52][OH:53])[C@@H:45]([OH:46])[C@H:40]1[OH:41]
Reactant: CC(=O)OC[C@H]1O[C@@H](OC(C)=O)[C@H](OC(C)=O)[C@@H]1OC(C)=O
Reactant: Nc1nc[nH]c(=O)n1
Agent: C[O-]
Agent: C[Si](C)(C)Cl
Agent: C[Si](C)(C)N[Si](C)(C)C
Solvent: CC#N
Solvent: CO
Product: Nc1ncn([C@@H]2O[C@H](CO)[C@@H](O)[C@H]2O)c(=O)n1
Reaction time: 20 h

Procedure:
A mixture of 5-azacytosine (5.0 g, 44.6 mol), HMDS (6.3 mL, 29.8 mol), and TMSCl (6 mL, 47.3 mmol) in acetonitrile (78 mL) was heated to reflux for 20 hours under an inert atmosphere. TMS-triflate (9 mL, 50 mmol) and 1,2,3,5-tetra-O-acetyl-β-D-ribofuranose (14.2 g, 44.6 mmol were added directly to the silylated 5-azacytosine in acetonitrile. The addition was performed at ambient temperature and under an inert atmosphere. The reaction mixture was maintained under stirring for 20 hours, then poured over a pre-cooled (0–5° C.) sodium bicarbonate solution (10%, 500 mL). The resulting mixture was extracted with dichloromethane (3×75 mL). The combined organic extract was washed with cooled (0–5° C.) 10% sodium bicarbonate (2×25 mL) and brine (2×25 mL), then dried over magnesium sulfate (10.0 g), filtered, and the filtrate concentrated in vacuum to dryness. The off-white foam dissolved in methanol (120 mL) was treated with a solution of 25% sodium methoxide in methanol (1.0 g, 4.62 mmol). Soon a white solid started to separate. The suspension was stirred at ambient temperature for 15 hours, then the solid was filtered off, washed with methanol (3×5 mL) and anhydrous ether (2×5 mL), then dried in vacuum. The crude 5-azacytidine (4.5 g, 41.3%) was further purified from DMSO and methanol (for details see Example 4).