Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: CC(C[AlH]CC(C)C)C.C1(C)C=CC=CC=1.C([O:19][C:20](=O)/[CH:21]=[CH:22]/[C:23]1[CH:32]=[CH:31][C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[N:24]=1)C.CO>C1COCC1>[N:24]1[C:25]2[C:30](=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH:31]=[CH:32][C:23]=1/[CH:22]=[CH:21]/[CH2:20][OH:19]
Reactant: CCOC(=O)/C=C/c1ccc2ccccc2n1
Agent: CC(C)C[AlH]CC(C)C
Solvent: CO
Solvent: C1CCOC1
Solvent: Cc1ccccc1
Product: OC/C=C/c1ccc2ccccc2n1
Reaction time: 3 h
Yield: 55 %

Procedure:
Under an atmosphere of nitrogen a 1M solution of DIBAL-H in toluene (82 ml, 82 mmol) was added dropwise at −70° C. over 20 min. to a stirred solution of (E)-3-quinolin-2-yl-acrylic acid ethyl ester (12.5 g, 55 mmol) in dry THF (400 ml) and the mixture stirred for 3 h. Methanol (100 ml) was added, and the mixture was concentrated in vacuo. The residue was dissolved in 1N HCl (500 mL) and ethyl acetate (100 mL). The aqueous phase was separated and added 1 N NaOH to pH 8. The product was extracted with dichloromethane. The combined organic phases were washed with water, dried (MgSO4), filtered and concentrated in vacuo. The residue was dissolved in ethyl acetate, treated with activated charcoal, filtered, and concentrated in vacuo yielding 5.6 g (56%) of (E)-3-quinolin-2-yl-prop-2-en-1-ol.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][C:3]=1[N+:9]([O-:11])=[O:10].[Cl:12][C:13]1[CH:18]=[CH:17][C:16]([CH2:19]Br)=[CH:15][CH:14]=1>>[Cl:12][C:13]1[CH:18]=[CH:17][C:16]([CH2:19][O:8][C:5]2[CH:6]=[CH:7][C:2]([Cl:1])=[C:3]([N+:9]([O-:11])=[O:10])[CH:4]=2)=[CH:15][CH:14]=1
Reactant: O=[N+]([O-])c1cc(O)ccc1Cl
Reactant: Clc1ccc(CBr)cc1
Product: O=[N+]([O-])c1cc(OCc2ccc(Cl)cc2)ccc1Cl

Procedure:
A solution of 4-chloro-3-nitro-phenol was reacted with 1-chloro-4-brommethyl benzene using the conditions described in Example 237C to provide 4-(4-chloro-benzyloxy)-1-chloro-2-nitro-benzene which was treated sequentially using the procedures from Examples 237D and 237E to provide the title compound.
Reaction SMILES: Br[C:2]1[CH:3]=[CH:4][C:5](=[O:8])[NH:6][CH:7]=1.[C:9](=[N:22][NH2:23])([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1>[C:10]1([C:9]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[N:22][NH:23][C:2]2[CH:3]=[CH:4][C:5](=[O:8])[NH:6][CH:7]=2)[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1
Reactant: O=c1ccc(Br)c[nH]1
Reactant: NN=C(c1ccccc1)c1ccccc1
Agent: CC(C)(C)[O-]
Agent: CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21
Agent: [Na+]
Solvent: Cc1ccccc1
Product: O=c1ccc(NN=C(c2ccccc2)c2ccccc2)c[nH]1
Yield: 28.5 %

Procedure:
5-Bromo-2(1H)-pyridone (2.0 g, 11.5 mmol) in 25 mL dry toluene was treated with benzophenone hydrazone (2.50 g, 12.7 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (200 mg, 0.345 mmol), and sodium tert-butoxide (2.2 g, 23 mmol). The mixture was degassed with argon for 15 minutes. Added Pd(II)(OAc)2 (80 mg, 0.345 mmol) and stirred at 90° C. for 16 hours. Extracted using EtOAc/H2O (3×150 mL EtOAc, lx 150 mL brine). Dried using Na2SO4 and then purified by flash chromatography (silica, 0-12% MeOH/DCM) to afford 5-(2-(diphenylmethylene)hydrazinyl)pyridin-2(1H)-one (950 mg, 3.28 mmol, 29%). 1H NMR (300 MHz, DMSO-d6) δ 11.12 (s, 1H), 8.49 (s, 1H), 7.61-7.25 (m, 12H), 6.31 (d, 1H); LC-MS (ESI) m/z 290 (M+H)+.
Reaction SMILES: [CH3:1][O:2][CH:3]([O:12][CH3:13])[C:4](=[O:11])[CH2:5][C:6]([O:8][CH2:9][CH3:10])=[O:7].C(O)[C:15]1[CH:20]=[CH:19]C=[CH:17][CH:16]=1.P([O-])([O-])([O-])=O>CN(C)C1C=CN=CC=1.C1(C)C=CC=CC=1>[CH3:1][O:2][CH:3]([O:12][CH3:13])[C:4](=[O:11])[CH2:5][C:6]([O:8][CH2:9][C:10]1[CH:19]=[CH:20][CH:15]=[CH:16][CH:17]=1)=[O:7]
Reactant: CCOC(=O)CC(=O)C(OC)OC
Reactant: OCc1ccccc1
Agent: CN(C)c1ccncc1
Agent: O=P([O-])([O-])[O-]
Solvent: Cc1ccccc1
Product: COC(OC)C(=O)CC(=O)OCc1ccccc1

Procedure:
2.68 g (14.1 mmol) of ethyl 4,4-dimethoxy-3-oxo-butyrate, 3.62 ml (34.9 mmol) of benzyl alcohol and 244 mg (2.0 mmol) of 4-dimethylaminopyridine were heated under reflux in 40 ml of toluene for three nights. A phosphate buffer solution was added to the obtained reaction solution. After the extraction with ethyl acetate, the organic layer was washed with a saturated aqueous salt solution and then dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by the silica gel chromatography (hexane/ethyl acetate=9:1) to obtain the title compound.
Reaction SMILES: [F:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:4]([C:5]([OH:7])=O)[C:3]=1[C:11]([OH:13])=[O:12].C(OC(=O)C)(=O)C>>[F:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:4]2[C:5]([O:13][C:11](=[O:12])[C:3]=12)=[O:7]
Reactant: O=C(O)c1cccc(F)c1C(=O)O
Solvent: CC(=O)OC(C)=O
Product: O=C1OC(=O)c2c(F)cccc21

Procedure:
15 g of 3-fluorophthalic acid are mixed with 16.6 g of acetic anhydride and refluxed for 3 hrs. After removal of unreacted acetic anhydride the remaining white solid is recrystalized from toluene.
Reaction SMILES: [OH:1][C@H:2]1[CH2:7][CH2:6][CH2:5][N:4]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:3]1.[H-].[Na+].I[CH3:18]>O1CCCC1.C(OCC)(=O)C>[CH3:18][O:1][C@H:2]1[CH2:7][CH2:6][CH2:5][N:4]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:3]1
Reactant: CI
Reactant: CC(C)(C)OC(=O)N1CCC[C@H](O)C1
Agent: [H-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: CO[C@H]1CCCN(C(=O)OC(C)(C)C)C1
Reaction time: 0.42 h
Yield: 72.2 %

Procedure:
To a solution of 1,1-dimethylethyl (3S)-3-hydroxypiperidine-1-carboxylate (Preparation 127, 1.8 g, 9.2 mmol) in anhydrous tetrahydrofuran (40 ml) was added sodium hydride (60% dispersion in oil, 0.39 g, 9.2 mmol) in portions. The resulting mixture was stirred for 25 min then iodomethane (2.83 g, 20 mmol) was added dropwise and the reaction mixture was stirred for 17 h. The reaction mixture was diluted with ethyl acetate (200 ml) and washed with brine (5% solution, 200 ml). The aqueous layer, was extracted with ethyl acetate (2×50 ml) and the combined organic extracts were dried (MgSO4) and concentrated in vacuo. The resulting yellow oil was purified by flash chromatography on silica gel (100 g) eluting with dichloromethane:methanol (100:1 and then 50:1) to give a yellow oil. The trace of iodine was removed by dissolving the product in diethyl ether (60 ml) and washing with aqueous sodium metabisulphite (5% solution, 1×40 ml), water (2×40 ml) and aqueous sodium hydrogen carbonate (5% solution, 40 ml). The organic extracts were dried (MgSO4) and concentrated in vacuo to give the desired product as a colourless oil (1.43 g).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH:12]=[CH:11][CH:10]=[C:9]2[CH:13]=O)=[CH:4][CH:3]=1.[CH3:15][CH:16]([CH3:32])[C:17]([NH:19][C:20]1[CH:25]=[CH:24][CH:23]=[C:22]([CH:26]2[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]2)[CH:21]=1)=[O:18]>>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[CH:12]=[CH:11][CH:10]=[C:9]2[CH2:13][N:29]2[CH2:30][CH2:31][CH:26]([C:22]3[CH:21]=[C:20]([NH:19][C:17](=[O:18])[CH:16]([CH3:15])[CH3:32])[CH:25]=[CH:24][CH:23]=3)[CH2:27][CH2:28]2)=[CH:6][CH:7]=1
Reactant: CC(C)C(=O)Nc1cccc(C2CCNCC2)c1
Reactant: O=Cc1cccn1-c1ccc(Cl)cc1
Product: CC(C)C(=O)Nc1cccc(C2CCN(Cc3cccn3-c3ccc(Cl)cc3)CC2)c1

Procedure:
Prepared by Procedure F and Scheme R using 1-(4-chlorophenyl)-1H-pyrrole-2-carbaldehyde and 2-methyl-N-[3-(4-piperidinyl)phenyl]propanamide: ESMS m/e: 436.0 (M+H)+.
Reaction SMILES: C([O:5][C@@H:6]([C@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14]1[CH:19]=[CH:18][N:17]=[C:16]([F:20])[N:15]=1)[CH3:7])(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[F:20][C:16]1[N:15]=[C:14]([N:9]2[C@@H:8]([C@H:6]([OH:5])[CH3:7])[CH2:12][O:11][C:10]2=[O:13])[CH:19]=[CH:18][N:17]=1
Reactant: C[C@@H](OC(C)(C)C)[C@H]1COC(=O)N1c1ccnc(F)n1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: C[C@@H](O)[C@H]1COC(=O)N1c1ccnc(F)n1
Temperature: 25 °C
Reaction time: 1 h
Yield: 90.3 %

Procedure:
To a round bottom flask containing (R)-4-((R)-1-(tert-butoxy)ethyl)-3-(2-fluoropyrimidin-4-yl)oxazolidin-2-one (2.1 g, 7.41 mmol) was added DCM (18.5 mL) and TFA (18.5 mL). The resulting reaction mixture stirred for 1 hr at room temperature. The volatiles were then removed and the residue neutralized with a saturated solution of NaHCO3. The aqueous mixture was then extracted with EtOAc. The organic phases were combined, washed with water, brine, dried (Na2SO4), filtered and concentrated to a colorless residue of (R)-3-(2-fluoropyrimidin-4-yl)-4-((R)-1-hydroxyethyl)oxazolidin-2-one (1.52 g, 6.69 mmol, 90% yield) which crystallizes upon standing. LCMS m/z 228.0 (M+H)+, Rt 0.44 min.
Reaction SMILES: Cl.Cl.Cl.[CH3:4][C:5]1[N:10]=[C:9]([N:11]2[CH2:16][CH2:15][N:14]([CH2:17][CH2:18][C@H:19]3[CH2:24][CH2:23][C@H:22]([NH2:25])[CH2:21][CH2:20]3)[CH2:13][CH2:12]2)[C:8]2[CH:26]=[CH:27][O:28][C:7]=2[CH:6]=1.[CH3:29][O:30][CH2:31][CH2:32][C:33](O)=[O:34]>>[CH3:29][O:30][CH2:31][CH2:32][C:33]([NH:25][C@H:22]1[CH2:21][CH2:20][C@H:19]([CH2:18][CH2:17][N:14]2[CH2:13][CH2:12][N:11]([C:9]3[C:8]4[CH:26]=[CH:27][O:28][C:7]=4[CH:6]=[C:5]([CH3:4])[N:10]=3)[CH2:16][CH2:15]2)[CH2:24][CH2:23]1)=[O:34]
Reactant: Cc1cc2occc2c(N2CCN(CC[C@H]3CC[C@H](N)CC3)CC2)n1
Reactant: COCCC(=O)O
Agent: Cl
Product: COCCC(=O)N[C@H]1CC[C@H](CCN2CCN(c3nc(C)cc4occc34)CC2)CC1

Procedure:
The title compound, white solid (100 mg, 78%), MS (ISP) m/z=429.4 [(M+H)+], mp 158° C., was prepared in accordance with the general method of example 32 from trans-4-{2-[4-(6-methyl-furo[3,2-c]pyridin-4-yl)-piperazin-1-yl]-ethyl}-cyclohexylamine trihydrochloride (intermediate D) (136 mg, 0.3 mmol) and 3-methoxypropionic acid.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([OH:14])=[CH:10][CH:9]=2)=[CH:4][CH:3]=1.C([O:17][C:18]([C:20]1[N:21]=[C:22]([CH2:25]Br)[S:23][CH:24]=1)=[O:19])C>>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[CH:13]=[CH:12][C:11]([O:14][CH2:25][C:22]3[S:23][CH:24]=[C:20]([C:18]([OH:19])=[O:17])[N:21]=3)=[CH:10][CH:9]=2)=[CH:6][CH:7]=1
Reactant: CCOC(=O)c1csc(CBr)n1
Reactant: Oc1ccc(-c2ccc(Cl)cc2)cc1
Product: O=C(O)c1csc(COc2ccc(-c3ccc(Cl)cc3)cc2)n1

Procedure:
2-(4′-Chloro-biphenyl-4-yloxymethyl)-thiazole-4-carboxylic acid was prepared using general procedure B from 4-chloro-4′-hydroxybiphenyl (available from TCI America, Portland, Oreg.) and 2-bromomethyl-thiazole-4-carboxylic acid ethyl ester (Intermediate 3). Yield: 82 mg. Mass spectrum (ES) MH+=346.
Reaction SMILES: C(OC([N:8]1[CH2:12][C@H:11]([O:13][Si](C(C)(C)C)(C)C)[CH2:10][C@@H:9]1[C:21](=[O:40])[NH:22][C:23]1[CH:28]=[CH:27][C:26]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=2[S:35]([CH3:38])(=[O:37])=[O:36])=[CH:25][C:24]=1[F:39])=O)(C)(C)C.FC(F)(F)C(O)=O>C(Cl)Cl>[F:39][C:24]1[CH:25]=[C:26]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=2[S:35]([CH3:38])(=[O:36])=[O:37])[CH:27]=[CH:28][C:23]=1[NH:22][C:21]([C@H:9]1[CH2:10][C@@H:11]([OH:13])[CH2:12][NH:8]1)=[O:40]
Reactant: CC(C)(C)OC(=O)N1C[C@H](O[Si](C)(C)C(C)(C)C)C[C@@H]1C(=O)Nc1ccc(-c2ccccc2S(C)(=O)=O)cc1F
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CS(=O)(=O)c1ccccc1-c1ccc(NC(=O)[C@H]2C[C@@H](O)CN2)c(F)c1

Procedure:
(2R,4R)-4-(tert-Butyl-dimethyl-silanyloxy)-2-(3-fluoro-2′-methanesulfonyl-biphenyl-4-ylcarbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (0.8 g, 1.35 mmol) was dissolved in 30 mL DCM, added 10 mL trifluoroacetic acid and stirred reaction at ambient temperature for 90 minutes. Solution was concentrated to yield title compound as an amber oil. (100% crude yield) APCI (AP−): 434.1 (M−H)−.
Reaction SMILES: C([O:3][C:4](=[O:30])[C@H:5]([CH2:26][CH:27]([CH3:29])[CH3:28])[NH:6][C:7]([O:9][CH2:10][CH2:11][O:12][CH2:13][CH2:14][O:15][CH2:16][CH2:17][O:18][CH2:19][CH2:20][O:21][CH2:22][CH2:23][O:24][CH3:25])=[O:8])C.C(OC(=O)[C@H](CC(C)C)N)C>>[CH3:25][O:24][CH2:23][CH2:22][O:21][CH2:20][CH2:19][O:18][CH2:17][CH2:16][O:15][CH2:14][CH2:13][O:12][CH2:11][CH2:10][O:9][C:7]([NH:6][C@H:5]([C:4]([OH:30])=[O:3])[CH2:26][CH:27]([CH3:28])[CH3:29])=[O:8]
Reactant: CCOC(=O)[C@H](CC(C)C)NC(=O)OCCOCCOCCOCCOCCOC
Agent: CCOC(=O)[C@@H](N)CC(C)C
Product: COCCOCCOCCOCCOCCOC(=O)N[C@@H](CC(C)C)C(=O)O

Procedure:
Following the reaction in an analogous manner to Reference Example 2(3) and using N-((14-methoxy-3,6,9,12-tetraoxa-tetradecanyloxy)carbonyl-L-leucine ethyl ester in place of N-((3S)-tetrahydrofuran-3-yloxy)carbonyl)-L-leucine ethyl ester, there was obtained N-((14-methoxy-3,6,9,12-tetraoxa-tetradecanyloxy)carbonyl)-L-leucine as a colorless oil.
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][CH:4]([N:7]2[CH:11]=[C:10]([C:12]3[CH:17]=[N:16][C:15]([NH2:18])=[C:14]4[O:19][C:20]([C:22]5[CH2:23][CH2:24][NH:25][CH2:26][CH:27]=5)=[CH:21][C:13]=34)[CH:9]=[N:8]2)[CH2:3][CH2:2]1>CO.[Pd]>[NH:25]1[CH2:24][CH2:23][CH:22]([C:20]2[O:19][C:14]3=[C:15]([NH2:18])[N:16]=[CH:17][C:12]([C:10]4[CH:9]=[N:8][N:7]([CH:4]5[CH2:5][CH2:6][NH:1][CH2:2][CH2:3]5)[CH:11]=4)=[C:13]3[CH:21]=2)[CH2:27][CH2:26]1
Reactant: Nc1ncc(-c2cnn(C3CCNCC3)c2)c2cc(C3=CCNCC3)oc12
Agent: [Pd]
Solvent: CO
Product: Nc1ncc(-c2cnn(C3CCNCC3)c2)c2cc(C3CCNCC3)oc12
Temperature: 25 °C
Reaction time: 2 h

Procedure:
A suspension of 4-[1-(piperidin-4-yl)-1H-pyrazol-4-yl]-2-(1,2,3,6-tetrahydropyridin-4-yl)furo[2,3-c]pyridin-7-amine (30 mg, 0.082 mmol) and 10% Pd/C (5 mg) in MeOH (10 mL) was stirred at RT under a H2 balloon for 2 h. The reaction mixture was filtered and concentrated to afford the title compound. 1H NMR (400 MHz, CD3OD): δ 8.29 (s, 1H), 7.89 (s, 1H), 7.73 (s, 1H), 7.19 (s, 1H), 4.62 (m, 1H), 3.49 (m, 4H), 3.34 (m, 1H), 3.15 (m, 4H), 2.29 (m, 6H), 2.07 (m, 2H); MS (ESI): 367.1 [M+H]+.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH2:7][NH2:8].C(N(CC)CC)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH:40]12[CH2:45][CH:44]1[CH2:43][N:42]([C:46]1[N:51]=[C:50]([NH:52][CH2:53][C:54]3[CH:59]=[CH:58][C:57]([O:60][CH3:61])=[C:56]([Cl:62])[CH:55]=3)[C:49]([C:63](O)=[O:64])=[CH:48][N:47]=1)[CH2:41]2>C1COCC1>[CH:44]12[CH2:45][CH:40]1[CH2:41][N:42]([C:46]1[N:51]=[C:50]([NH:52][CH2:53][C:54]3[CH:59]=[CH:58][C:57]([O:60][CH3:61])=[C:56]([Cl:62])[CH:55]=3)[C:49]([C:63]([NH:8][CH2:7][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=3)=[O:64])=[CH:48][N:47]=1)[CH2:43]2
Reactant: NCc1ccccn1
Reactant: COc1ccc(CNc2nc(N3CC4CC4C3)ncc2C(=O)O)cc1Cl
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: COc1ccc(CNc2nc(N3CC4CC4C3)ncc2C(=O)NCc2ccccn2)cc1Cl
Reaction time: 18 h
Yield: 24 %

Procedure:
In THF (50 mL) were dissolved 2-(3-azabicyclo[3.1.0]hexan-3-yl)-4-((3-chloro-4-methoxybenzyl)amino)pyrimidine-5-carboxylic acid, pyridine-2-ylmethylamine (69 mg, 0.64 mmol) and triethylamine (0.2 mL). The solution was cooled in an ice bath and HATU (266 mg, 0.70 mmol) was then added. The reaction was conducted at ambient temperature for 18 h. The reaction mixture was concentrated, followed by addition of water and extraction with ethyl acetate. The organic phase was dried, concentrated and purified by silica gel column chromatography (DCM/methanol=50/1) to give 2-(3-azabicyclo[3.1.0]hexan-3-yl)-4-((3-chloro-4-methoxybenzyl)amino)-N-(pyridin-2-ylmethyl)pyrimidine-5-formamide (60 mg, 24% yield).
Reaction SMILES: C[O:2][C:3]([C:5]1([C:18]2[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][CH:19]=2)[CH2:10][CH2:9][N:8]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:7][CH2:6]1)=O.[H-].[Al+3].[Li+].[H-].[H-].[H-].O>CCOCC>[C:14]([O:13][C:11]([N:8]1[CH2:7][CH2:6][C:5]([C:18]2[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][CH:19]=2)([CH2:3][OH:2])[CH2:10][CH2:9]1)=[O:12])([CH3:17])([CH3:15])[CH3:16]
Reactant: COC(=O)C1(c2ccc(Cl)cc2)CCN(C(=O)OC(C)(C)C)CC1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: CCOCC
Solvent: O
Product: CC(C)(C)OC(=O)N1CCC(CO)(c2ccc(Cl)cc2)CC1
Temperature: 0 °C
Reaction time: 3 h
Yield: 46 %

Procedure:
To a chilled solution of 4-(4-chloro-phenyl)-piperidine-1,4-dicarboxylic acid 1-tert-butyl ester 4-methyl ester (700 mg, 1.98 mmol) in 6 ml ether was added dropwise 2 ml lithium aluminium hydride 1M solution in ether. The reaction was stirred at 0° C. for 3 hours, then water (100 ml) was slowly added. The resulting gel was filtered and the aqueous filtrate was extracted three times with ether. The combined organic layers were dried with magnesium sulfate and concentrated under vacuum. Recovered oil was purified by silica gel chromatography, eluting with hexane-ethyl acetate (6:4) to give the title compound (297 mg, 46%).
Reaction SMILES: O.[NH2:2][NH2:3].[C:4]([NH:23]N)(=[O:22])[CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11]/[CH:12]=[CH:13]\[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH3:21]>>[C:4]([NH2:23])(=[O:22])[CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11]/[CH:12]=[CH:13]\[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH3:21].[NH2:2][NH2:3]
Reactant: CCCCCCCC/C=C\CCCCCCCC(=O)NN
Agent: NN
Solvent: O
Product: CCCCCCCC/C=C\CCCCCCCC(N)=O
Temperature: 160 °C
Reaction time: 1 h

Procedure:
To 282 g (1.0 mole) of Industrene 105 oleic acid (available from Humko Chemical Division of Witco Corp.) was added 46.0 g (0.92 mole) of hydrazine monohydrate (0.92 moles hydrazine per mole of oleic acid). The mixture was warmed slowly to 160° C. while stripping with nitrogen and stirred for one hour to give 299 g of hydrazine oleamide (or oleic hydrazide). The silver wear and copper corrosion results are reported in Table II below.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][C:11]=1[O:12][CH3:13])[C:8](=[O:14])O[C:6]2=[O:15].[NH2:16][CH2:17][C:18]([OH:20])=[O:19]>C1(C)C=CC=CC=1>[CH3:13][O:12][C:11]1[CH:10]=[C:9]2[C:5](=[CH:4][C:3]=1[O:2][CH3:1])[C:6](=[O:15])[N:16]([CH2:17][C:18]([OH:20])=[O:19])[C:8]2=[O:14]
Reactant: COc1cc2c(cc1OC)C(=O)OC2=O
Reactant: NCC(=O)O
Solvent: Cc1ccccc1
Product: COc1cc2c(cc1OC)C(=O)N(CC(=O)O)C2=O
Temperature: 180 °C
Yield: 53.5 %

Procedure:
A suspension of 5,6-dimethoxyisobenzofuran-1,3-dione (491 mg, 2.359 mmol) and 2-aminoacetic acid (195 mg, 2.59 mmol) in toluene (10 ml) was heated under MW irradiation at 180° C. for 7 hours. The precipitate was collected by filtration, washed with toluene (5 ml) and dried to afford 2-(5,6-dimethoxy-1,3-dioxoisoindolin-2-yl)acetic acid as a off-white powder (335 mg, 1.263 mmol, 54% yield). MS/ESI+ 265.9 [MH]+.
Reaction SMILES: [Cl:1][C:2]1[C:3]2[CH:10]=[CH:9][NH:8][C:4]=2[N:5]=[CH:6][N:7]=1.[I:11]N1C(=O)CCC1=O>C(Cl)Cl>[Cl:1][C:2]1[C:3]2[C:10]([I:11])=[CH:9][NH:8][C:4]=2[N:5]=[CH:6][N:7]=1
Reactant: O=C1CCC(=O)N1I
Reactant: Clc1ncnc2[nH]ccc12
Solvent: ClCCl
Product: Clc1ncnc2[nH]cc(I)c12
Temperature: 25 °C
Reaction time: 8 h
Yield: 79 %

Procedure:
To a suspension of 4-chloro-7H-pyrrolo[2,3-d]pyrimidine (70.5 g, 0.45 mol) in DCM (1.8 L) was added N-iodosuccinimide (120 g, 0.54 mol) in portions. After addition, the mixture was stirred at room temperature overnight. The solid was filtered and washed with water (250 mL), MeOH (280 mL) and CH2Cl2 (280 mL) sequentially. The solid was dried under vacuum to afford 4-chloro-5-iodo-7H-pyrrolo[2,3-d]pyrimidine as a brown solid in 79% yield, 107 g.
Reaction SMILES: [Cl:1][C:2]1[C:22]([OH:23])=[CH:21][C:5]2[C:6]([C:9]([C:11]3[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[C:13]([O:19][CH3:20])[CH:12]=3)=[O:10])=[CH:7][O:8][C:4]=2[C:3]=1[Cl:24].[N+]([O-])(O)=[O:26].O.C(Cl)(Cl)Cl.CO>C(O)(=O)C>[Cl:1][C:2]1[C:22](=[O:23])[C:21](=[O:26])[C:5]2[C:6]([C:9](=[O:10])[C:11]3[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[C:13]([O:19][CH3:20])[CH:12]=3)=[CH:7][O:8][C:4]=2[C:3]=1[Cl:24]
Reactant: O=[N+]([O-])O
Reactant: COc1ccc(C(=O)c2coc3c(Cl)c(Cl)c(O)cc23)cc1OC
Solvent: CC(=O)O
Solvent: ClC(Cl)Cl
Solvent: O
Product: COc1ccc(C(=O)c2coc3c2C(=O)C(=O)C(Cl)=C3Cl)cc1OC
Temperature: 60 °C

Procedure:
To a suspension of compound 16 (100 mg, 0.27 mmol) in glacial acetic acid (2 mL) at room temperature was added nitric acid (0.1 mL, d 1.35) dropwise with vigorous stirring. The mixture was heated at 60° C. for 3 h, allowed to cool to room temperature, and poured into cold water. The resulting precipitate was filtered and recrystallized to furnish compound SKC-BF-10 (45 mg, 43%) as a red solid. TLC Rf=0.6 (CHCl3-MeOH, 9:1); 1H NMR (CDCl3) δ 7.89 (s, 1H), 7.57 (app s, 1H), 7.35 (app d, 1H), 6.84 (d, J=8.3 Hz, 1H), 3.96 (s, 6H); MS (ES) m/z 381 (M+H)+.
Reaction SMILES: COC([N:5]1[CH2:10][CH2:9][C@H:8]([N:11](C(=O)CC)[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[F:18])[C@H:7]([CH3:23])[CH2:6]1)=O.[OH-].[Na+]>Br>[CH3:23][C@H:7]1[C@@H:8]([NH:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[F:18])[CH2:9][CH2:10][NH:5][CH2:6]1
Reactant: CCC(=O)N(c1ccccc1F)[C@H]1CCN(C(=O)OC)C[C@H]1C
Agent: Br
Agent: [Na+]
Agent: [OH-]
Product: C[C@@H]1CNCC[C@@H]1Nc1ccccc1F
Temperature: 0 °C

Procedure:
A suspension of cis-1-methoxycarbonyl-3-methyl-4-[(1-oxo-propyl)-2-fluorophenylamino]-piperidine (3.2 g, 9.89 mmol) in 48% aqueous HBr (20 ml) is refluxed for two hours. Upon heating the mixture dissolution occurs. The solution is cooled to 0° C. and 5N NaOH is added until the pH is between 11 and 12. The aqueous phase is extracted with methylene chloride (5×) and the combined organics dried over sodium sulfate and concentrated to give cis-3-methyl-4-(2-fluorophenylamino)-piperidine as an oil: 2.0 g; 97%.
Reaction SMILES: [OH-].[Li+].[C:3]([O:7][C:8]([NH:10][C:11]([CH3:28])([CH3:27])[CH2:12][C:13]1[N:17]([CH2:18][CH2:19][O:20][CH3:21])[N:16]=[C:15]([C:22]([O:24]CC)=[O:23])[CH:14]=1)=[O:9])([CH3:6])([CH3:5])[CH3:4]>CO.O>[C:3]([O:7][C:8]([NH:10][C:11]([CH3:28])([CH3:27])[CH2:12][C:13]1[N:17]([CH2:18][CH2:19][O:20][CH3:21])[N:16]=[C:15]([C:22]([OH:24])=[O:23])[CH:14]=1)=[O:9])([CH3:6])([CH3:4])[CH3:5]
Reactant: CCOC(=O)c1cc(CC(C)(C)NC(=O)OC(C)(C)C)n(CCOC)n1
Agent: [Li+]
Agent: [OH-]
Solvent: CO
Solvent: O
Product: COCCn1nc(C(=O)O)cc1CC(C)(C)NC(=O)OC(C)(C)C
Reaction time: 48 h
Yield: 37.6 %

Procedure:
Lithium hydroxide (17.1 g, 407 mmol) was added to a solution of ethyl 5-{2-[(tert-butoxycarbonyl)amino]-2-methylpropyl}-1-(2-methoxyethyl)-1H-pyrazole-3-carboxylate (37.6 g, 102 mmol) in methanol (141 mL) and water (47 mL). The reaction mixture was stirred for 2 days and then most of the methanol was removed under reduced pressure. The aqueous residue was cooled in an ice bath and then combined with 1 N hydrochloric acid (350 mL) and tert-butyl methyl ether. The layers were separated. The volume of the organic layer was reduced under vacuum and then diluted with hexanes. A precipitate was isolated by filtration, washed with water, and suction dried to provide 13.09 g of 5-{2-[(tert-butoxycarbonyl)amino]-2-methylpropyl}-1-(2-methoxyethyl)-1H-pyrazole-3-carboxylic acid as a white solid. The aqueous layer was extracted with chloroform while maintaining the pH of the aqueous layer at pH 4-5 by the addition of 1 N hydrochloric acid. The chloroform extracts were combined, dried over sodium sulfate and magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was dissolved in tert-butyl methyl ether, diluted with hexanes, and then concentrated under reduced pressure. A white solid was isolated by filtration, washed with hexanes, and suction dried to provide an additional 21.8 g of product.
Reaction SMILES: Cl.[C:2](=N)(OCC)[CH3:3].[F:8][C:9]1[CH:14]=[CH:13][C:12]([NH2:15])=[C:11]([NH2:16])[CH:10]=1>C(O)C>[CH3:2][C:3]1[NH:16][C:11]2[CH:10]=[C:9]([F:8])[CH:14]=[CH:13][C:12]=2[N:15]=1
Reactant: Nc1ccc(F)cc1N
Reactant: CCOC(C)=N
Agent: Cl
Solvent: CCO
Product: Cc1nc2ccc(F)cc2[nH]1
Temperature: 25 °C
Reaction time: 8 h
Yield: 51.3 %

Procedure:
Ethyl acetimidate hydrochloride (37.1 g, 0.3 mol) was added to a stirred suspension of 4-fluoro-ortho-phenylenediamine (12.6 g, 0.1 mol) in ethanol (150 ml) at 0° C. The mixture was allowed to warm up to room temperature and stirred overnight. The solvent was removed under reduced pressure and the residue extracted into ethyl acetate (100 ml), washed with water (3×100 ml), dried over anhydrous magnesium sulphate, filtered and evaporated. Crystallisation from ethyl acetate gave 2-methyl-5-fluorobenzimidazole (7.7 g, 51%) as a brown crystalline solid.