Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[C:11]([CH:12]=[O:13])=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1.[BH4-].[Na+]>CO>[Cl:1][C:2]1[C:11]([CH2:12][OH:13])=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1
Reactant: O=Cc1cc2ccccc2nc1Cl
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Product: OCc1cc2ccccc2nc1Cl
Reaction time: 2 h

Procedure:
A suspension of 2-chloro-3-quinolinecarbaldehyde (19.2 g, 100 mmol) in methanol (400 ml) is treated with sodium borohydride (5.7 g, 150 mmol). After agitation for 2 hours at ambient temperature, the reaction medium is concentrated under reduced pressure then taken up in water, filtered, washed with water and with ethanol in order to produce, after drying under reduced pressure, 15.8 g (81%) of a white solid, m.p. 166° C.
Reaction SMILES: [C:1]([O:4][C:5](=[O:7])[CH3:6])(=O)[CH3:2].[N:8]1[CH:13]=[CH:12][C:11](CCO)=[CH:10][CH:9]=1.C(N(CC)CC)C>C(Cl)Cl.CN(C1C=CC=CN=1)C>[C:5]([O:4][CH2:1][CH2:2][C:11]1[CH:12]=[CH:13][N:8]=[CH:9][CH:10]=1)(=[O:7])[CH3:6]
Reactant: CC(=O)OC(C)=O
Reactant: OCCc1ccncc1
Agent: CN(C)c1ccccn1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(=O)OCCc1ccncc1
Temperature: 0 °C
Reaction time: 1.5 h

Procedure:
To a solution of 11.3 ml of acetic anhydride in 100 ml of methylene chloride was added approximately 125 mg of dimethylaminopyridine, and the solution was cooled to 0° C. In a separate container 12.2 g (0.099 mol) of 4-pyridineethanol was suspended in 80 ml of methylene chloride and 12.14 g (0.120 mol, 16.7 ml) of triethylamine was added. This mixture was added to the acetic anhydride solution slowly by pipet. The resulting mixture was stirred at room temperature for approximately 90 minutes and quenched with about 100 ml of water. The mixture was placed in a separatory funnel and the organic layer was isolated and washed two times with 100 ml portions of water. The aqueous layers were combined and extracted two times with methylene chloride and one time with diethyl ether. The organic extracts were combined, dried over anhydrous sodium sulfate, filtered and concentrated under vacuum to provide 16.2 g of the desired compound. Purification by high pressure liquid chromatography provided 11.19 g of 4-pyridineethanol acetate.
Reaction SMILES: [CH3:1][C:2]1[O:6][N:5]=[C:4]([C:7]([OH:9])=O)[CH:3]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[NH2:43][C:44]1[CH:49]=[CH:48][C:47]([OH:50])=[C:46]([C:51]2[N:55]([CH3:56])[N:54]=[CH:53][CH:52]=2)[CH:45]=1.C(Cl)[Cl:58]>>[Cl:58][C:52]1[CH:53]=[N:54][N:55]([CH3:56])[C:51]=1[C:46]1[CH:45]=[C:44]([NH:43][C:7]([C:4]2[CH:3]=[C:2]([CH3:1])[O:6][N:5]=2)=[O:9])[CH:49]=[CH:48][C:47]=1[OH:50]
Reactant: Cc1cc(C(=O)O)no1
Reactant: ClCCl
Reactant: Cn1nccc1-c1cc(N)ccc1O
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Product: Cc1cc(C(=O)Nc2ccc(O)c(-c3c(Cl)cnn3C)c2)no1
Temperature: 25 °C
Reaction time: 0.08 h
Yield: 59 %

Procedure:
To a solution of 5-methylisoxazole-3-carboxylic acid (284.0 mg, 2236.0 μmol) dissolved in DCM(10.0 mL) was added HATU (1020.0 mg, 2683.0 μmol) followed by DIEA (586 μl, 3353 μmol). The solution was stirred at room temperature for 5 minutes. 4-amino-2-(1-methyl-1H-pyrazol-5-yl)phenol (500.00 mg, 2236 μmol) was added and the reaction mixture was stirred at 25° C. for 15 hours. The reaction mixture was subjected to purification by column chromatography (ethyl acetate:hexane 50:50) to afford the title compound as an off-white solid in 59.0% yield. LCMS m/z=333.2 (M+H), 1H NMR (400 MHz, DMSO-d6) δ ppm 2.69 (s, 3 H), 3.66 (s, 3 H), 6.64 (s, 1 H), 7.00 (d, J=8.84 Hz, 1 H), 7.61 (s, 1 H), 7.64 (d, J=2.53 Hz, 1 H), 7.73 (dd, J=8.84, 2.53 Hz, 1 H), 10.04 (s, 1 H), 10.60 (s, 1 H).
Reaction SMILES: C(Cl)Cl.[OH:4][CH2:5][CH2:6][CH2:7][CH2:8]/[CH:9]=[C:10](\[CH3:16])/[C:11]([O:13][CH2:14][CH3:15])=[O:12].N1C=CN=C1.[Si:22](Cl)([C:25]([CH3:28])([CH3:27])[CH3:26])([CH3:24])[CH3:23]>CN(C)C=O>[O:4]([CH2:5][CH2:6][CH2:7][CH2:8]/[CH:9]=[C:10](\[CH3:16])/[C:11]([O:13][CH2:14][CH3:15])=[O:12])[Si:22]([C:25]([CH3:28])([CH3:27])[CH3:26])([CH3:24])[CH3:23]
Reactant: CC(C)(C)[Si](C)(C)Cl
Reactant: CCOC(=O)/C(C)=C/CCCCO
Agent: c1c[nH]cn1
Solvent: ClCCl
Solvent: CN(C)C=O
Product: CCOC(=O)/C(C)=C/CCCCO[Si](C)(C)C(C)(C)C
Reaction time: 0.33 h
Yield: 98.8 %

Procedure:
To a methylene chloride solution (300 ml) of Ester 3 (13.91 g; 0.0748 mol), 43 ml of DMF (dimethylformamide) and imidazole (7.6 g; 0.112 mol) are added and the whole is stirred until imidazole is fully dissolved. Tert-butyldimethylsilyl chloride (13.5 g; 0.0897 mol) is then added thereto and the whole is stirred for 20 min. After stirring, the resultant solution is quenched using a buffer solution (100 ml) and the organic compound is extracted three times with ethyl acetate, followed by the wash of the organic layer in a saturated saline solution and drying over anhydrous magnesium sulfate. After anhydrous magnesium sulfate is filtered and the solvent is distilled off under reduced pressure, the residue is separated and purified by column chromatography (developing solution, ethyl acetate:hexane=1:1) to produce Ester 4 (22.16 g; 0.0739 mol) of 99% in yield.
Reaction SMILES: [CH3:1][C:2]1([CH3:37])[CH2:6][CH2:5][N:4]([C:7]2[CH:8]=[C:9]([C:14]3[N:15]=[C:16]4[C:22]([C:23](=[O:28])[C:24]([CH3:27])([CH3:26])[CH3:25])=[CH:21][N:20]([CH2:29][O:30][CH2:31][CH2:32][Si:33]([CH3:36])([CH3:35])[CH3:34])[C:17]4=[N:18][CH:19]=3)[CH:10]=[C:11]([OH:13])[CH:12]=2)[CH2:3]1.[CH3:38][C:39]1([CH3:46])[O:43][CH:42]([CH2:44]O)[CH2:41][O:40]1.CSCCO>>[CH3:38][C:39]1([CH3:46])[O:43][CH:42]([CH2:44][O:13][C:11]2[CH:10]=[C:9]([C:14]3[N:15]=[C:16]4[C:22]([C:23](=[O:28])[C:24]([CH3:25])([CH3:26])[CH3:27])=[CH:21][N:20]([CH2:29][O:30][CH2:31][CH2:32][Si:33]([CH3:36])([CH3:35])[CH3:34])[C:17]4=[N:18][CH:19]=3)[CH:8]=[C:7]([N:4]3[CH2:5][CH2:6][C:2]([CH3:37])([CH3:1])[CH2:3]3)[CH:12]=2)[CH2:41][O:40]1
Reactant: CC1(C)OCC(CO)O1
Reactant: CC1(C)CCN(c2cc(O)cc(-c3cnc4c(n3)c(C(=O)C(C)(C)C)cn4COCC[Si](C)(C)C)c2)C1
Agent: CSCCO
Product: CC1(C)CCN(c2cc(OCC3COC(C)(C)O3)cc(-c3cnc4c(n3)c(C(=O)C(C)(C)C)cn4COCC[Si](C)(C)C)c2)C1

Procedure:
This material was prepared starting from 1-[2-[3-(3,3-dimethyl-pyrrolidin-1-yl)-5-hydroxy-phenyl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-2,2-dimethyl-propan-1-one via Mitsunobu type alkylation similar to that which was described above, but using “(2,2-dimethyl-[1,3]dioxolan-4-yl)-methanol” in place of “2-methylsulfanyl-ethanol”.
Reaction SMILES: [C:1]1([O:11][C:12]2[CH:17]=[CH:16][C:15]([NH2:18])=[CH:14][N:13]=2)[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.[F:19][C:20]1[CH:30]=[CH:29][CH:28]=[C:27]([F:31])[C:21]=1[C:22]([N:24]=[C:25]=[O:26])=[O:23]>C1(C)C=CC=CC=1>[C:1]1([O:11][C:12]2[CH:17]=[CH:16][C:15]([NH:18][C:25]([NH:24][C:22](=[O:23])[C:21]3[C:27]([F:31])=[CH:28][CH:29]=[CH:30][C:20]=3[F:19])=[O:26])=[CH:14][N:13]=2)[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1
Reactant: Nc1ccc(Oc2cccc3ccccc23)nc1
Reactant: O=C=NC(=O)c1c(F)cccc1F
Solvent: Cc1ccccc1
Product: O=C(NC(=O)c1c(F)cccc1F)Nc1ccc(Oc2cccc3ccccc23)nc1

Procedure:
A mixture of 2.5 g. of 2-(1-naphthoxy)-5-amino pyridine and 8.13 ml. of toluene was heated up to 50° C. To this resulting homgeneous solution was added a solution of 3.1 g. of 2,6-difluorobenzoyl isocyanate in 2 ml. of toluene. The resulting mixture was heated at 80° for 1.5 hours, cooled, and filtered to give 4.7 g. of white crystals; mp. 223.5°-224.0°.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]2[Se:10][C:9]([CH3:11])=[N:8][C:7]=2[CH:12]=1.[C:13]1([CH3:24])[CH:18]=[CH:17][C:16]([S:19]([O:22]C)(=[O:21])=[O:20])=[CH:15][CH:14]=1>C(Cl)(Cl)Cl>[C:13]1([CH3:24])[CH:14]=[CH:15][C:16]([S:19]([O-:22])(=[O:20])=[O:21])=[CH:17][CH:18]=1.[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]2[Se:10][C:9]([CH3:11])=[N+:8]([CH3:13])[C:7]=2[CH:12]=1
Reactant: COc1ccc2[se]c(C)nc2c1
Reactant: COS(=O)(=O)c1ccc(C)cc1
Solvent: ClC(Cl)Cl
Product: COc1ccc2[se]c(C)[n+](C)c2c1
Product: Cc1ccc(S(=O)(=O)[O-])cc1
Yield: 189.8 %

Procedure:
Into a sealed tube were placed 2.26 g (10.0 mmoles) of 5-methoxy-2-methylbenzoselenazole, 1.93 g (10.4 mmoles) of methyl paratoluenesulfonate and 10 ml of chloroform. The resulting mixture was treated in the same manner as in Reference Example 4, giving 4.07 g (yield: 99%) of 5-methoxy-2,3-dimethylbenzoselenazolium paratoluenesulfonate as a purple powder.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[CH:14]=[C:13]([N:15]3[CH2:20][CH2:19]N[CH2:17][CH2:16]3)[N:12]=[C:11]([N:21]3[CH2:26][CH2:25][N:24]([CH2:27][CH2:28][CH3:29])[CH2:23][CH2:22]3)[N:10]=2)[CH:5]=[CH:6][C:7]=1[F:8].Cl[C:31]1[C:36]([CH3:37])=[CH:35][C:34]([N+:38]([O-:40])=[O:39])=[CH:33][N:32]=1.[CH3:41]CN(C(C)C)C(C)C>CC(N(C)C)=O>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[N:10]=[C:11]([N:21]3[CH2:22][CH2:23][N:24]([CH2:27][CH2:28][CH3:29])[CH2:25][CH2:26]3)[N:12]=[C:13]([N:15]3[CH2:16][CH2:17][CH:41]([C:31]4[C:36]([CH3:37])=[CH:35][C:34]([N+:38]([O-:40])=[O:39])=[CH:33][N:32]=4)[CH2:19][CH2:20]3)[CH:14]=2)[CH:5]=[CH:6][C:7]=1[F:8]
Reactant: CCN(C(C)C)C(C)C
Reactant: CCCN1CCN(c2nc(-c3ccc(F)c(Cl)c3)cc(N3CCNCC3)n2)CC1
Reactant: Cc1cc([N+](=O)[O-])cnc1Cl
Solvent: CC(=O)N(C)C
Product: CCCN1CCN(c2nc(-c3ccc(F)c(Cl)c3)cc(N3CCC(c4ncc([N+](=O)[O-])cc4C)CC3)n2)CC1

Procedure:
Heat a mixture of 4-(3-chloro-4-fluoro-phenyl)-6-piperazin-1-yl-2-(4-propyl-piperazin-1-yl)-pyrimidine (300 mg, 0.72 mmol), 2-chloro-3-methyl-5-nitro-pyridine (149 mg, 0.86 mmol) and DIEA (186 mg, 1.44 mmol) in DMA (4 mL) for 16 h at 110° C. Cool, partition between 10% NaOH and EtOAc and wash the organic layer with additional NaOH solution (3×). Dry the organic layer (Na2SO4) and concentrate under reduced pressure to afford the title compound.
Reaction SMILES: [C:1]([C:3]1[CH:4]=[CH:5][CH:6]=[C:7]2[C:11]=1[NH:10][C:9]1[C:12](=[O:36])[N:13]([CH2:22][C:23]([NH:25][CH:26]([CH:33]([CH3:35])[CH3:34])[CH:27]([OH:32])[C:28]([F:31])([F:30])[F:29])=[O:24])[C:14]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)=[CH:15][C:8]2=1)#[N:2].Cl.CN(C)CCCN=C=NCC.ClC(Cl)C(O)=O.C(OCC)(=O)C>CS(C)=O.C1(C)C=CC=CC=1>[C:1]([C:3]1[CH:4]=[CH:5][CH:6]=[C:7]2[C:11]=1[NH:10][C:9]1[C:12](=[O:36])[N:13]([CH2:22][C:23]([NH:25][CH:26]([CH:33]([CH3:34])[CH3:35])[C:27](=[O:32])[C:28]([F:30])([F:29])[F:31])=[O:24])[C:14]([C:16]3[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=3)=[CH:15][C:8]2=1)#[N:2]
Reactant: CC(C)C(NC(=O)Cn1c(-c2ccccc2)cc2c([nH]c3c(C#N)cccc32)c1=O)C(O)C(F)(F)F
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: O=C(O)C(Cl)Cl
Solvent: Cc1ccccc1
Solvent: CS(C)=O
Solvent: CCOC(C)=O
Product: CC(C)C(NC(=O)Cn1c(-c2ccccc2)cc2c([nH]c3c(C#N)cccc32)c1=O)C(=O)C(F)(F)F
Reaction time: 2 h
Yield: 77 %

Procedure:
To a solution of 2-(8-cyano-1-oxo-3-phenyl-1,2-dihydropyrido[3,4-b]indol-2-yl)-N-(3,3,3-trifluoro-2-hydroxy-1-isopropylpropyl)acetamide (0.3 g) in dimethyl sulfoxide (2 mL) and toluene (2 mL) was added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (1.4 g) and dichloroacetic acid (0.23 mL), and the resulting solution was allowed to stir for 2 hours. The mixture was poured into ethyl acetate and was washed (1N hydrochloric acid, H2O), dried, and evaporated. The resulting material was chromatographed, with methanol:dichloromethane (3:97) as the eluent, to give the title compound (0.23 g) as a yellow solid; TLC: Rf =0.5, methanol:dichloromethane (5:95);
Reaction SMILES: N[C:2]1[C:11]2[C:6](=[N:7][C:8]([OH:12])=[CH:9][N:10]=2)[N:5]=[C:4]([CH2:13][O:14][CH2:15][O:16][CH3:17])[N:3]=1.[OH-:18].[K+].Cl>O>[OH:12][C:8]1[N:7]=[C:6]2[C:11]([C:2](=[O:18])[NH:3][C:4]([CH2:13][O:14][CH2:15][O:16][CH3:17])=[N:5]2)=[N:10][CH:9]=1
Reactant: [OH-]
Reactant: COCOCc1nc(N)c2ncc(O)nc2n1
Agent: Cl
Agent: [K+]
Solvent: O
Product: COCOCc1nc2nc(O)cnc2c(=O)[nH]1

Procedure:
1.1 g (0.00464 mole) of 4-amino-7-hydroxy-2-(methoxymethoxymethyl)pteridine is added to a solution of 1.5 g (0.0267 mole) of potassium hydroxide in 20 ml of water. The mixture is refluxed for 8 hours. After cooling, the reaction mixture is acidified with 10% hydrochloric acid to pH 5.5. The precipitate formed is isolated by filtration and washed with water. It is extracted with a mixture of 50 ml of ethanol and 60 ml of N,N-dimethylformamide under reflux. This extract, concentrated under reduced pressure, is recrystallized from a mixture of ethanol and N,N-dimethylformamide. Yld: 0.2 g (18%), m.p. 224°-226° C. (ethanol).
Reaction SMILES: NC1C=CC=CC=1.[CH:8]([S:11][C:12]1[CH:18]=[CH:17][C:15]([NH2:16])=[CH:14][C:13]=1[C:19]([F:22])([F:21])[F:20])([CH3:10])[CH3:9].C(N(CC)CC)C.[CH3:30][C:31]1([C:34](Cl)=[O:35])[CH2:33][CH2:32]1>O1CCCC1>[CH:8]([S:11][C:12]1[CH:18]=[CH:17][C:15]([NH:16][C:34]([C:31]2([CH3:30])[CH2:33][CH2:32]2)=[O:35])=[CH:14][C:13]=1[C:19]([F:22])([F:20])[F:21])([CH3:10])[CH3:9]
Reactant: CC1(C(=O)Cl)CC1
Reactant: CC(C)Sc1ccc(N)cc1C(F)(F)F
Solvent: CCN(CC)CC
Solvent: Nc1ccccc1
Solvent: C1CCOC1
Product: CC(C)Sc1ccc(NC(=O)C2(C)CC2)cc1C(F)(F)F
Temperature: 0 °C
Yield: 79 %

Procedure:
To a stirred solution containing 23.5 g (0.1 mole) of the aniline prepared in (b) above and 10.1 g (0.1 mole) of triethylamine in 150 ml of tetrahydrofuran was added dropwise over 5 minutes 11.9 g (0.1 mole) of 1-methylcyclopropylcarboxylic chloride. This addition was exothermic to 55° C. The mixture was refluxed for 1 hour, poured into ice water and filtered. The filter cake was recrystallized from hexane to give 25 g (79%) of product as a colorless crystalline solid, m.p. 103°-105° C.
Reaction SMILES: [F:1][C:2]1[N:7]=[C:6]([CH:8]([OH:27])[CH:9]([CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([O:20][C:21]([F:26])([F:25])[CH:22]([F:24])[F:23])[CH:15]=2)C(O)=O)[CH:5]=[CH:4][CH:3]=1.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=O)C=CC=CC=1.C([N:47]([CH2:50]C)CC)C.[OH2:52]>O1CCCC1>[F:1][C:2]1[N:7]=[C:6]([CH:8]2[O:27][C:50](=[O:52])[NH:47][CH:9]2[CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([O:20][C:21]([F:25])([F:26])[CH:22]([F:23])[F:24])[CH:15]=2)[CH:5]=[CH:4][CH:3]=1
Reactant: O=C(O)C(Cc1cccc(OC(F)(F)C(F)F)c1)C(O)c1cccc(F)n1
Reactant: O
Reactant: CCN(CC)CC
Agent: [N-]=[N+]=NP(=O)(c1ccccc1)c1ccccc1
Solvent: C1CCOC1
Product: O=C1NC(Cc2cccc(OC(F)(F)C(F)F)c2)C(c2cccc(F)n2)O1
Yield: 65 %

Procedure:
To a solution of (2RS,3RS)-3-(6-fluoropyridin-2-yl)-3-hydroxy-2-((3-(1,1,2,2-tetrafluoroethoxy)phenyl)methyl)propionic acid (3.6 g, 9.20 mmol) in tetrahydrofuran (90 ml) were added diphenylphosphoryl azide (2.18 ml, 10.1 mmol) and triethylamine (1.93 ml, 13.8 mmol), and the mixture was heated under reflux for 2 hrs. The reaction solution was allowed to cool and water (200 ml) was added. The mixture was extracted with ethyl acetate (100 ml×2). The extract was washed successively with 1N hydrochloric acid, saturated aqueous sodium hydrogen carbonate and saturated brine, dried over anhydrous magnesium sulfate and evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=1:1). Recrystallization from ethyl acetate-hexane gave (4RS,5RS)-5-(6-fluoropyridin-2-yl)-4-((3-(1,1,2,2-tetrafluoroethoxy)phenyl)methyl)-1,3-oxazolidin-2-one (2.34 g, 65%).
Reaction SMILES: [C:1]([O:6]C)(=[O:5])[C:2]([CH3:4])=[CH2:3].[C:8]([O:12]CCCC)(=[O:11])[CH:9]=[CH2:10]>O.O.O.O.O.O.[Co](Cl)Cl.CCC(C)=O>[C:1]([O-:6])(=[O:5])[C:2]([CH3:4])=[CH2:3].[C:8]([O-:12])(=[O:11])[CH:9]=[CH2:10]
Reactant: C=CC(=O)OCCCC
Reactant: C=C(C)C(=O)OC
Agent: Cl[Co]Cl
Solvent: CCC(C)=O
Solvent: O
Product: C=C(C)C(=O)[O-]
Product: C=CC(=O)[O-]

Procedure:
Equal amounts of (5 gms. each) of methyl methacrylate and butyl acrylate were used, 1% (by weight) of AIBN (azoisobutyronitrile) were dissolved in 2.5 ml. MEK was added to the test tube and blanketed by nitrogen flushing. 480 ppm of cobalt chloride hexahydrate (CoCl2.6H2O) containing catalyst solution 1-A were added to the test tube and further flushed by N2 for 30 minutes.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11]([S:31][C:32]2[CH:37]=[CH:36][C:35]([CH3:38])=[CH:34][CH:33]=2)([CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][N:19]2[CH2:27][C:26]3[C:21](=[CH:22][C:23]([O:29][CH3:30])=[C:24]([OH:28])[CH:25]=3)[CH2:20]2)[C:12]#[N:13])[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].C1(C)C=CC(S(O[CH2:49][CH2:50][Cl:51])(=O)=O)=CC=1>>[Cl:51][CH2:50][CH2:49][O:28][C:24]1[CH:25]=[C:26]2[C:21](=[CH:22][C:23]=1[O:29][CH3:30])[CH2:20][N:19]([CH2:18][CH2:17][CH2:16][CH2:15][CH2:14][C:11]([C:5]1[CH:6]=[CH:7][C:8]([O:9][CH3:10])=[C:3]([O:2][CH3:1])[CH:4]=1)([S:31][C:32]1[CH:33]=[CH:34][C:35]([CH3:38])=[CH:36][CH:37]=1)[C:12]#[N:13])[CH2:27]2
Reactant: Cc1ccc(S(=O)(=O)OCCCl)cc1
Reactant: COc1cc2c(cc1O)CN(CCCCCC(C#N)(Sc1ccc(C)cc1)c1ccc(OC)c(OC)c1)C2
Product: COc1ccc(C(C#N)(CCCCCN2Cc3cc(OC)c(OCCCl)cc3C2)Sc2ccc(C)cc2)cc1OC
Yield: 73 %

Procedure:
The procedure of Example of 32 is used with 0.45 g of α-(3,4-dimethoxyphenyl)-1,3-dihydro-5-hydroxy-6-methoxy-α-[(4-methylphenyl)thio]-2H-isoindole-2-heptanenitrile and 0.65 g of 2-chloroethyl p-toluenesulfonate. This affords 0.367 g of the desired product as a light brown oil.
Reaction SMILES: [C:1]([O:5][C:6](=[O:18])[NH:7][C:8]1([C:16]#[CH:17])[CH2:13][O:12][C:11]([CH3:15])([CH3:14])[O:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].C#CCCCCCC.[C:27]12([C:37]3[CH:42]=[C:41](I)[CH:40]=[CH:39][C:38]=3[O:44][CH:45]([CH3:47])[CH3:46])[CH2:36][CH:31]3[CH2:32][CH:33]([CH2:35][CH:29]([CH2:30]3)[CH2:28]1)[CH2:34]2.IC1C=C2C(=CC=1)CN(C(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)C2>>[C:1]([O:5][C:6](=[O:18])[NH:7][C:8]1([C:16]#[C:17][C:41]2[CH:40]=[CH:39][C:38]([O:44][CH:45]([CH3:47])[CH3:46])=[C:37]([C:27]34[CH2:36][CH:31]5[CH2:32][CH:33]([CH2:35][CH:29]([CH2:30]5)[CH2:28]3)[CH2:34]4)[CH:42]=2)[CH2:13][O:12][C:11]([CH3:15])([CH3:14])[O:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2]
Reactant: C#CC1(NC(=O)OC(C)(C)C)COC(C)(C)OC1
Reactant: CC(C)Oc1ccc(I)cc1C12CC3CC(CC(C3)C1)C2
Agent: C#CCCCCCC
Agent: Ic1ccc2c(c1)CN(C(c1ccccc1)(c1ccccc1)c1ccccc1)C2
Product: CC(C)Oc1ccc(C#CC2(NC(=O)OC(C)(C)C)COC(C)(C)OC2)cc1C12CC3CC(CC(C3)C1)C2
Yield: 58 %

Procedure:
When tert-butyl-5-ethynyl-2,2-dimethyl-1,3-dioxan-5-ylcarbamate was substituted for 1-octyne and the product of Step A was substituted for 5-iodo-2-tritylisoindoline in Example 2, Step D, the similar process afforded the title compound in 58% yield, as pale paste. 1H-NMR (CDCl3) 1.35 (d, 6H, J=6.01 Hz); 1.43 (s, 3H); 1.47 (s, 9H); 1.48 (s, 3H); 1.74 (s, 6H); 2.06 (s, 9H); 3.99 (d, 2H, J=11.45 Hz); 4.08 (d, 2H, J=11.51 Hz); 4.59-4.64 (m, 1H); 5.17 (broad s, 1H); 6.72 (d, 1H, J=8.61 Hz); 7.21 (dd, 1H, J=2.08, 8., Hz); 7.25 (d, 1H, J=2.09 Hz).
Reaction SMILES: [H-].[Na+].[Cl:3][C:4]1[CH:12]=[C:11]2[C:7]([CH:8]=[CH:9][NH:10]2)=[CH:6][C:5]=1[F:13].[CH3:14][C@H:15]1[CH2:17][O:16]1.O>O1CCCC1.CCOCC>[Cl:3][C:4]1[CH:12]=[C:11]2[C:7]([CH:8]=[CH:9][N:10]2[CH2:14][C@@H:15]([OH:16])[CH3:17])=[CH:6][C:5]=1[F:13]
Reactant: C[C@H]1CO1
Reactant: Fc1cc2cc[nH]c2cc1Cl
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Solvent: CCOCC
Product: C[C@H](O)Cn1ccc2cc(F)c(Cl)cc21
Reaction time: 1 h
Yield: 79 %

Procedure:
A suspension of 0.11 g of sodium hydride dispersion in 15 ml of tetrahydrofuran was treated with 0.5 g of 6-chloro-5-fluoroindole at 0° and stirred at this temperature for 1 hour. After the addition of 0.42 ml of (S)-methyloxirane the reaction mixture was stirred at room temperature for 85 hours and subsequently treated with water. The mixture was diluted with ether, washed with water and with saturated sodium chloride solution and the organic phase was dried over sodium sulfate. After removal of the solvent the residue was chromatographed over 25 g of silica gel with toluene-ethyl acetate (19:1). There was obtained 0.54 g (79%) of (S)-1-(6-chloro-5-fluoro-indol-1-yl)-propan-2-ol as beige crystals (m.p. 99°-101°).
Reaction SMILES: [CH3:1][S:2](Cl)(=[O:4])=[O:3].[F:6][CH2:7][CH2:8][CH2:9][OH:10]>C(Cl)Cl>[CH3:1][S:2]([O:10][CH2:9][CH2:8][CH2:7][F:6])(=[O:4])=[O:3]
Reactant: CS(=O)(=O)Cl
Reactant: OCCCF
Solvent: ClCCl
Product: CS(=O)(=O)OCCCF
Temperature: 2.5 °C
Reaction time: 2 h
Yield: 93.5 %

Procedure:
A solution of methanesulfonyl chloride (1.714 ml, 22.00 mmol) in DCM (5 ml) was added dropwise to a stirred cold (0° C.) solution of 3-fluoropropan-1-ol (1.562 g, 20 mmol) and TEA (3.35 ml, 24.00 mmol) in DCM (20 ml). The mixture was stirred at 0-5° C. for ˜2 h and washed with water, satd. NaHCO3, water, brine and dried (MgSO4). Evaporation of DCM gave 3-fluoropropyl methanesulfonate as a colorless oil (2.92 g, 93.6%). Neat potassium thioacetate (2.74 g, 24.00 mmol) was added to a stirred solution of 3-fluoropropyl methanesulfonate (2.9 g) in DMSO (20 ml) and the mixture stirred overnight. Product was extracted with ether (2×25 ml), washed with water, brine and dried (MgSO4). Evaporation of ether gave S-3-fluoropropyl ethanethioate as a light brown oil. Chlorine gas was bubbled into cold (−10° C.) stirred two-phase solution of S-3-fluoropropyl ethanethioate (1.0 g, 7.34 mmol) in DCM (5 ml) and Water (5.00 ml) until green color appeared in aqueous phase and maintained for 1-2 h. Layers separated and aq. layer re-extracted with DCM (2×10 ml). Combined DCM extracts were washed with 10% NaHSO3 solution, water, brine and dried (MgSO4). Evaporation of DCM gave the intermediate, 3-fluoropropane-1-sulfonyl chloride as a light brown oil (405 mg, 34%) which was treated with an. NH3 solution (10 ml, 0.5M in dioxane) and stirred for 30-45 min. Precipitated NH4Cl was filtered off and the filtrate was evaporated to dryness to afford 3-fluoropropane-1-sulfonamide as a light brown oil (265 mg).
Reaction SMILES: [O:1]=[C:2]1[NH:10][C:5]2=[N:6][CH:7]=[CH:8][CH:9]=[C:4]2[N:3]1[CH:11]1[CH2:16][CH2:15][N:14]([C:17]2[N:22]=[CH:21][N:20]=[C:19]([C:23](O)=[O:24])[CH:18]=2)[CH2:13][CH2:12]1.[NH:26]1[C:34]2[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=2)[CH:28]([CH2:35][OH:36])[CH2:27]1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>CN(C=O)C>[OH:36][CH2:35][CH:28]1[C:29]2[C:34](=[CH:33][CH:32]=[CH:31][CH:30]=2)[N:26]([C:23]([C:19]2[N:20]=[CH:21][N:22]=[C:17]([N:14]3[CH2:15][CH2:16][CH:11]([N:3]4[C:4]5[C:5](=[N:6][CH:7]=[CH:8][CH:9]=5)[NH:10][C:2]4=[O:1])[CH2:12][CH2:13]3)[CH:18]=2)=[O:24])[CH2:27]1
Reactant: O=C(O)c1cc(N2CCC(n3c(=O)[nH]c4ncccc43)CC2)ncn1
Reactant: OCC1CNc2ccccc21
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[B-](F)(F)F
Solvent: CN(C)C=O
Product: O=C(c1cc(N2CCC(n3c(=O)[nH]c4ncccc43)CC2)ncn1)N1CC(CO)c2ccccc21
Temperature: 25 °C
Reaction time: 5 h

Procedure:
85 mg (0.25 mmol) 6-[4-(2-oxo-2,3-dihydroimidazo[4,5-b]pyridin-1-yl)-piperidin-1-yl]-pyrimidine-4-carboxylic acid and 50 mg (0.32 mmol) (2,3-dihydro-1H-indol-3-yl)-methanol in 50 μL (0.36 mmol) TEA and 0.90 mL DMF were combined with 85 mg (0.27 mmol) TBTU and stirred for 5 h at RT. Then the reaction mixture was purified by preparative HPLC-MS. The product-containing fractions were combined and freeze-dried.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([NH2:9])=[CH:5][CH:4]=1.[N+:10]([C:13]1[CH:21]=[CH:20][C:16]([C:17](Cl)=[O:18])=[CH:15][CH:14]=1)([O-:12])=[O:11].O>N1C=CC=CC=1>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:17](=[O:18])[C:16]2[CH:15]=[CH:14][C:13]([N+:10]([O-:12])=[O:11])=[CH:21][CH:20]=2)=[CH:5][CH:4]=1
Reactant: COc1ccc(N)cc1
Reactant: O=C(Cl)c1ccc([N+](=O)[O-])cc1
Solvent: O
Solvent: c1ccncc1
Product: COc1ccc(NC(=O)c2ccc([N+](=O)[O-])cc2)cc1
Yield: 73.6 %

Procedure:
12.3 g of p-anisidine were added in small fractions to a suspension of 18.6 g of 4-nitrobenzoic acid chloride in 100 ml of pyridine and the mixture was heated for 2 hours at reflux. After returning to ambient temperature, the solution was poured into 500 ml of iced water and the precipitate formed was separated and washed with water, then dried under reduced pressure at 80° C. to obtain 20 g of N-(4-methoxyphenyl)-4-nitrobenzamide melting at 200° C.