Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]1[O:3][C@@H:2]1[CH2:4][OH:5].[NH:6]1[CH2:11][CH2:10][O:9][CH2:8][CH2:7]1>C(O)C>[N:6]1([CH2:1][C@H:2]([OH:3])[CH2:4][OH:5])[CH2:11][CH2:10][O:9][CH2:8][CH2:7]1
Reactant: C1COCCN1
Reactant: OC[C@@H]1CO1
Solvent: CCO
Product: OC[C@@H](O)CN1CCOCC1
Temperature: 25 °C
Yield: 112.9 %

Procedure:
A solution of (R)-glycidol (0.33 mL, 5.0 mmol) and morpholine (0.65 mL, 7.5 mmol, 1.5 equiv.) in abs. ethanol was heated in a microwave for 4 min. at 140 0° C., cooled to room temperature and concentrated at 70° C. under a 12 mBar vacuum to afford (2S)-3-(4-morpholinyl)-1,2-propanediol (0.91 g, 113%): 1H NMR (CDCl3) δ 2.37 (dd, J=3.9, 12.5 Hz, 1H), 2.41-2.48 (m, 2H), 2.57 (dd, J=9.7, 12.5 Hz, 1H), 3.51 (dd, J=4.3, 11.4 Hz, 1H), 3.66-3.79 (m, 5H), 3.81-3.87 (m, 1H).
Reaction SMILES: C([O:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[O:15][N:14]=[C:13]([CH3:16])[N:12]=2)=[CH:7][CH:6]=1)C=C.[C:17]1(OC2C=CC=CC=2)[CH:22]=CC=C[CH:18]=1>C(OCC)C>[CH2:22]([C:10]1[CH:9]=[C:8]([C:11]2[O:15][N:14]=[C:13]([CH3:16])[N:12]=2)[CH:7]=[CH:6][C:5]=1[OH:4])[CH:17]=[CH2:18]
Reactant: c1ccc(Oc2ccccc2)cc1
Reactant: C=CCOc1ccc(-c2nc(C)no2)cc1
Solvent: CCOCC
Product: C=CCc1cc(-c2nc(C)no2)ccc1O
Reaction time: 0.2 h

Procedure:
5-(4-allyloxyphenyl)-3-methyl-1,2,4-oxadiazole (1.2 g) and diphenyl ether (5 ml) were warmed gently to give a solution. This stirred solution, under an atmosphere of argon, was immersed in an oil bath at 265° C. for 12 minutes. This procedure was repeated three times. The deep red solutions were combined, diluted with diethyl ether (100 ml) and extracted with aqueous 1M sodium hydroxide (3×20 ml). The alkaline extracts were combined, washed with ether (3×30 ml), cooled in ice-water, acidified with aqueous 5M hydrochloric acid (15 ml), and extracted with ether (3×60 ml). The ether extracts were combined, washed with saturated brine (25 ml), dried (Na2SO4) and evaporated. The residue was purified by flash column chromatography on silica gel using 20% ethyl acetate/n-pentane as eluent, to give 2-allyl-4-(3-methyl-1,2,4-oxadiazol-5-yl)phenol as a solid m.p. 135°-137° C.; microanalysis, found: C, 66.7; H, 5.8; N, 12.5%; C12H12N2O2 requires: C, 66.7; H, 5.6; N, 13.0%; NMR: 2.3-2.35(3H,s), 3.3-3.4(2H,d), 5.0-5.15(2H,m), 5.85-6.1(1H,m), 6.95-7.05(1H,d), 7.75-7.8(2H,m) and 10.4-10.5(1H,s); m/z 217 (M+H).
Reaction SMILES: [CH2:1]([O:4][C:5]1[CH:6]=[C:7]2[C:22](=[CH:23][CH:24]=1)[C:10]1[NH:11][N:12]=[C:13]([C:14]3[CH:21]=[CH:20][C:17]([C:18]#[N:19])=[CH:16][CH:15]=3)[C:9]=1[CH2:8]2)[CH:2]=[CH2:3].[N-:25]=[N+:26]=[N-:27].[Na+].N(CC)(CC)CC.Cl>CN(C=O)C>[CH2:1]([O:4][C:5]1[CH:6]=[C:7]2[C:22](=[CH:23][CH:24]=1)[C:10]1[NH:11][N:12]=[C:13]([C:14]3[CH:15]=[CH:16][C:17]([C:18]4[NH:27][N:26]=[N:25][N:19]=4)=[CH:20][CH:21]=3)[C:9]=1[CH2:8]2)[CH:2]=[CH2:3]
Reactant: C=CCOc1ccc2c(c1)Cc1c(-c3ccc(C#N)cc3)n[nH]c1-2
Reactant: [N-]=[N+]=[N-]
Agent: Cl
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: C=CCOc1ccc2c(c1)Cc1c(-c3ccc(-c4nnn[nH]4)cc3)n[nH]c1-2
Reaction time: 8 h
Yield: 28.6 %

Procedure:
A mixture of Example 62B (61.5 mg, 0.196 mmol), NaN3 (19.1 mg, 0.294 mmol), and Et3N.HCl (40.5 mg, 0.294 mmol) in DMF (2 mL) was heated at 140° C. for 4 hours. To this mixture were added more NaN3 (60.0 mg) and Et3N.HCl (120 mg). The reaction mixture was stirred overnight, cooled, and concentrated. The crude material was purified using the HPLC condition in Example 8 to give 20.0 mg (29%) of the desired product as brown solid. MS (DCI/NH3) m/z: 357.1 (M+H)+; 1H NMR (300 MHz, DMSO-d6) δ 3.90 (s, 2H), 4.53-4.71 (m, 2H), 5.29 (dd, J=10.51, 1.70 Hz, 1H), 5.44 (dd, J=17.29, 2.03 Hz, 1H), 6.07 (m, 1H), 6.98 (dd, J=8.31, 2.20 Hz, 1H), 7.22 (d, J=2.03 Hz, 1H), 7.57 (d, J=8.14 Hz, 1H), 8.02 (d, J=8.14 Hz, 2H), 8.16 (d, J=8.48 Hz, 2H), 13.22 (s, brd, 1H).
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH:8]([NH:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][N:26]=1)[CH:9]([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=1)[CH:10]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[OH:11].[C:31](O)(=[O:39])[CH2:32][CH2:33][CH2:34][CH2:35][C:36]([OH:38])=[O:37].C1(N=C=NC2CCCCC2)CCCCC1.N1(O)C2C=CC=CC=2N=N1>>[OH:11][CH:10]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[CH:9]([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=1)[CH:8]([C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1[NH:1][C:31]([CH2:32][CH2:33][CH2:34][CH2:35][C:36]([OH:38])=[O:37])=[O:39])[NH:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][N:26]=1
Reactant: O=C(O)CCCCC(=O)O
Reactant: Nc1ccccc1C(Nc1ccccn1)C(c1ccccn1)C(O)c1ccccc1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: On1nnc2ccccc21
Product: O=C(O)CCCCC(=O)Nc1ccccc1C(Nc1ccccn1)C(c1ccccn1)C(O)c1ccccc1

Procedure:
Prepared from 1.5 g of 3-(2-aminophenyl)-1-phenyl-2-pyridin-2-yl-3-(pyridin-2-ylamino)propan-1-ol, 3.4 g of hexanedioic acid, 1.04 g of dicyclohexylcarbodiimide and 640 mg of benzotriazol-1-ol, analogously to example II f) Product _of molecular weight 524.6 (C31H32N4O4); MS (ESI+): 525 (M+H+): (ESI−): 523 (M−H+)
Reaction SMILES: Br[C:2](=[CH2:13])[CH2:3][CH2:4][O:5][Si:6]([C:9]([CH3:12])([CH3:11])[CH3:10])([CH3:8])[CH3:7].C([Li])(C)(C)C.[Li].[F:20][C:21]1[CH:28]=[CH:27][C:26]([N+:29]([O-:31])=[O:30])=[CH:25][C:22]=1[CH:23]=[O:24]>C1COCC1>[Si:6]([O:5][CH2:4][CH2:3][C:2](=[CH2:13])[CH:23]([C:22]1[CH:25]=[C:26]([N+:29]([O-:31])=[O:30])[CH:27]=[CH:28][C:21]=1[F:20])[OH:24])([C:9]([CH3:12])([CH3:11])[CH3:10])([CH3:8])[CH3:7]
Reactant: C=C(Br)CCO[Si](C)(C)C(C)(C)C
Reactant: O=Cc1cc([N+](=O)[O-])ccc1F
Agent: [Li]
Agent: [Li]C(C)(C)C
Solvent: C1CCOC1
Product: C=C(CCO[Si](C)(C)C(C)(C)C)C(O)c1cc([N+](=O)[O-])ccc1F
Temperature: -78 °C
Reaction time: 0.17 h

Procedure:
To a solution of (3-bromobut-3-enyloxy)(tert-butyl)dimethylsilane from step A (3.14 g, 11.83 mmol) in THF (10 mL) at −78° C. was added tert-butyllithium (13.91 mL, 23.65 mmol, 1.70 M solution in hexanes) dropwise over a period of 5 min, and the reaction mixture was stirred at −78° C. for 10 min. The resulting lithium reagent was added dropwise to a solution of 2-fluoro-5-nitrobenzaldehyde (2 g, 11.83 mmol) in THF (10 mL) at −78° C., the reaction mixture was stirred at −78° C. for 20 min. The reaction mixture was then partitioned between ethyl acetate and water, and the organic layer was separated and concentrated to a crude product that was purified by chromatography eluting with 0-20% ethyl acetate/hexanes to give a mixture of starting material and the desired product. This mixture was further purified by preparative TLC eluting with 25% EtOAc/hexanes to give the title compound as a colorless oil (941 mg, 22% yield). 1H NMR (500 MHz, CDCl3) δ 8.57 (1H, m), 8.18 (1H, m), 7.15 (1H, m), 5.52 (1H, br. s), 5.16 (1H, s), 5.09 (1H, s), 4.96 (1H, m), 3.7-3.9 (2H, m), 2.20-2.35 (2H, m), 0.97 (9H, s), 0.17 (3H) and 0.15 (3H, s).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:17]=[N:16][C:15]3[C:14]([N:18]4[CH2:23][CH2:22][O:21][CH2:20][CH2:19]4)=[N:13][C:12]([C:24]4[CH:25]=[N:26][C:27]([NH:30][C:31](=[O:37])[O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[N:28][CH:29]=4)=[N:11][C:10]=3[CH:9]=2)[CH:5]=[CH:6][CH:7]=1.[CH:38]1([C:41](O)=[O:42])[CH2:40][CH2:39]1.CN(C=O)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>O>[CH:38]1([C:41]([NH:1][C:2]2[CH:3]=[C:4]([C:8]3[CH:17]=[N:16][C:15]4[C:14]([N:18]5[CH2:23][CH2:22][O:21][CH2:20][CH2:19]5)=[N:13][C:12]([C:24]5[CH:25]=[N:26][C:27]([NH:30][C:31](=[O:37])[O:32][C:33]([CH3:34])([CH3:36])[CH3:35])=[N:28][CH:29]=5)=[N:11][C:10]=4[CH:9]=3)[CH:5]=[CH:6][CH:7]=2)=[O:42])[CH2:40][CH2:39]1
Reactant: O=C(O)C1CC1
Reactant: CC(C)(C)OC(=O)Nc1ncc(-c2nc(N3CCOCC3)c3ncc(-c4cccc(N)c4)cc3n2)cn1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: O
Product: CC(C)(C)OC(=O)Nc1ncc(-c2nc(N3CCOCC3)c3ncc(-c4cccc(NC(=O)C5CC5)c4)cc3n2)cn1
Temperature: 25 °C
Reaction time: 12 h
Yield: 65.9 %

Procedure:
To a 25 mL round bottom flask, tert-butyl (5-(7-(3-aminophenyl)-4-morpholinopyrido[3,2-d]pyrimidin-2-yl)pyrimidin-2-yl)carbamate (0.2 g, 0.0004 mol), cyclopropane carboxylic acid (0.041 g, 0.00048 mol) and DMF (8 mL) were added. To the same flask, HATU (0.46 g, 0.0012 mol) and TEA (0.22 mL, 0.0016 mol) were added. The reaction mass was stirred at room temperature for 12 hours. The volatiles were evaporated to dryness under reduced pressure to provide a residue. The residue was stirred with water to provide a solid and the solid was collected by filtration. The solid was washed with diethyl ether to provide the crude product. The crude product was purified by flash column chromatography (1-2% methanol in chloroform) to afford the title compound (0.15 g, 66%). 1H NMR (300 MHz, DMSO-d6): δ 10.42 (br s, 2H), 9.48 (s, 1H), 9.07 (d, J=2.4 Hz, 1H), 8.31 (d, J=1.8 Hz, 1H), 8.20 (s, 1H), 7.47-7.67 (m, 3H), 4.57 (br s, 4H), 3.84 (s, 4H), 1.84-1.80 (m, 1H), 1.49 (s, 9H), 0.85-0.83 (m, 4H): LC-MS (ESI): Calculated mass: 568.2; Observed mass [M+H]+: 569.2 (RT=1.56 min).
Reaction SMILES: [C:1]([O:5][C@@H:6]1[C@:14]2([CH2:15][CH3:16])[C@H:9]([C@@H:10]3[CH2:24][CH2:23][C:22]4[CH:21]=[C:20]([O:25][CH3:26])[CH:19]=[CH:18][C:17]=4[C:11]3=[CH:12][CH2:13]2)[CH2:8][CH2:7]1)([CH3:4])([CH3:3])[CH3:2].[H][H]>[Pd].C(OCC)(=O)C>[C:1]([O:5][C@@H:6]1[C@:14]2([CH2:15][CH3:16])[C@H:9]([C@@H:10]3[CH2:24][CH2:23][C:22]4[CH:21]=[C:20]([O:25][CH3:26])[CH:19]=[CH:18][C:17]=4[C@H:11]3[CH2:12][CH2:13]2)[CH2:8][CH2:7]1)([CH3:4])([CH3:2])[CH3:3]
Reactant: [H][H]
Reactant: CC[C@]12CC=C3c4ccc(OC)cc4CC[C@H]3[C@@H]1CC[C@@H]2OC(C)(C)C
Agent: [Pd]
Solvent: CCOC(C)=O
Product: CC[C@]12CC[C@@H]3c4ccc(OC)cc4CC[C@H]3[C@@H]1CC[C@@H]2OC(C)(C)C

Procedure:
A mixture of 1g (2.82 mmoles) of (+)-17β-tert.butoxy-13β-ethyl-3-methoxygona-1,3,5(10),9(11)-tetraene, 0.25 g of 5% palladium on carbon and 35 ml of ethyl acetate was stirred in an atmosphere of hydrogen for 1 hr during which time a total of 74 ml of hydrogen was absorbed (70.5 ml theory). The catalyst was filtered with suction on Celite and the filter cake was washed well with ethyl acetate. Concentration of the combined filtrate and washes in vacuo gave 1.23 g of colorless solid. This material was chromatographed on 50 g of silica gel. Elution with 19:1 hexane:ether gave 0.925 g of colorless solid which was recrystallized from ethanol. This afforded 0.67 g of colorless plates, m.p. 121°-123°. [α] D25 +44.69°(c 1.016, CHCl3); uv max (95% EtOH) 278 nm (ε 2020), 287 (1860); ir (CHCl3) 1610, 1580, 1500, 1360 cm-1 ; nmr (CDCl3)δ 7.18 (m, 1), 6.68 (m, 2) 3.74 (s, 3), 3.51 (t, 1, J = Hz), 1.15 ppm (s); ms m/e 356 (M+).
Reaction SMILES: Cl[C:2]1[N:10]=[C:9]2[C:5]([N:6]=[C:7]([CH2:12][N:13]3[CH2:18][CH2:17][N:16]([S:19]([CH3:22])(=[O:21])=[O:20])[CH2:15][CH2:14]3)[N:8]2[CH3:11])=[C:4]([N:23]2[CH2:28][CH2:27][O:26][CH2:25][CH2:24]2)[N:3]=1.CC1(C)C(C)(C)OB([C:37]2[CH:38]=[CH:39][C:40]([NH2:43])=[N:41][CH:42]=2)O1>>[CH3:11][N:8]1[C:7]([CH2:12][N:13]2[CH2:14][CH2:15][N:16]([S:19]([CH3:22])(=[O:20])=[O:21])[CH2:17][CH2:18]2)=[N:6][C:5]2[C:9]1=[N:10][C:2]([C:37]1[CH:38]=[CH:39][C:40]([NH2:43])=[N:41][CH:42]=1)=[N:3][C:4]=2[N:23]1[CH2:24][CH2:25][O:26][CH2:27][CH2:28]1
Reactant: Cn1c(CN2CCN(S(C)(=O)=O)CC2)nc2c(N3CCOCC3)nc(Cl)nc21
Reactant: CC1(C)OB(c2ccc(N)nc2)OC1(C)C
Product: Cn1c(CN2CCN(S(C)(=O)=O)CC2)nc2c(N3CCOCC3)nc(-c3ccc(N)nc3)nc21

Procedure:
4-(2-Chloro-9-methyl-8-((4-(methylsulfonyl)piperazin-1-yl)methyl)-9H-purin-6-yl)morpholine (50 mg) was reacted with 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amine via General Procedure A and purified via reverse phase HPLC to give 29.1 mg 135 as a white solid. MS (Q1) 488.3 (M)+.
Reaction SMILES: CO[C:3]([CH3:14])(C)[CH:4]([NH:8][C:9]([O:11][CH3:12])=[O:10])[C:5]([OH:7])=[O:6].[NH2:15][CH:16](CCC#N)C(O)=O>>[C:16]([CH2:14][CH2:3][CH:4]([NH:8][C:9]([O:11][CH3:12])=[O:10])[C:5]([OH:7])=[O:6])#[N:15]
Reactant: N#CCCC(N)C(=O)O
Reactant: COC(=O)NC(C(=O)O)C(C)(C)OC
Product: COC(=O)NC(CCC#N)C(=O)O

Procedure:
This compound was prepared using the procedure used to prepare 3-Methoxy-2-methoxycarbonylamino-3-methyl-butyric acid using 2-Amino-4-cyano-butyric acid.
Reaction SMILES: [F:1][C:2]1[CH:9]=[C:8]([F:10])[CH:7]=[CH:6][C:3]=1[CH:4]=[O:5].[CH2:11](O)[CH2:12][OH:13].C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[F:1][C:2]1[CH:9]=[C:8]([F:10])[CH:7]=[CH:6][C:3]=1[CH:4]1[O:13][CH2:12][CH2:11][O:5]1
Reactant: O=Cc1ccc(F)cc1F
Reactant: OCCO
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: Cc1ccccc1
Product: Fc1ccc(C2OCCO2)c(F)c1

Procedure:
A stirred solution of 2,4-difluorobenzaldehyde (15.4 ml) in toluene (200 ml) was treated with ethylene glycol (23.2 ml) and p-toluene sulfonic acid (0.53 g). The reaction mixture was heated to reflux during 5 hrs (Dean-Stark trap), then it was cooled to r.t and poured onto ice. The organic layer was separated off, washed with 10% KHCO3-solution and brine, dried over MgSO4, filtered and concentrated to give 2-(2,4-difluoro-phenyl)-[1,3]dioxolane (26.8 g) as a light yellow oil. MS 186.1 ([M]+)
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][O:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.[OH:21][C:22]1[CH:23]=[C:24]([CH:27]=[CH:28][C:29]=1[O:30][CH3:31])[CH:25]=[O:26]>>[CH3:31][O:30][C:29]1[CH:28]=[CH:27][C:24]([CH:25]=[O:26])=[CH:23][C:22]=1[O:21][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][O:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1
Reactant: BrCCCCCCOCCCCCCc1ccccc1
Reactant: COc1ccc(C=O)cc1O
Product: COc1ccc(C=O)cc1OCCCCCCOCCCCCCc1ccccc1

Procedure:
Reaction of 1-bromo-6-(6-phenylhex-1-yloxy)hexane and 3-hydroxy-4-methoxy benzaldehyde analogous to the procedure of preparation 3, affords the title compound as a pale yellow oil. MS (m/z) 413.
Reaction SMILES: [C:1]([NH:8][C:9]1[CH:18]=[CH:17][C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[C:10]=1[N+:19]([O-:21])=[O:20])([C:3]([O:5][CH2:6][CH3:7])=[O:4])=[O:2].[N+:22]([O-])([OH:24])=[O:23]>S(=O)(=O)(O)O>[C:1]([NH:8][C:9]1[CH:18]=[CH:17][C:16]2[C:11](=[C:12]([N+:22]([O-:24])=[O:23])[CH:13]=[CH:14][CH:15]=2)[C:10]=1[N+:19]([O-:21])=[O:20])([C:3]([O:5][CH2:6][CH3:7])=[O:4])=[O:2]
Reactant: O=[N+]([O-])O
Reactant: CCOC(=O)C(=O)Nc1ccc2ccccc2c1[N+](=O)[O-]
Agent: O=S(=O)(O)O
Product: CCOC(=O)C(=O)Nc1ccc2cccc([N+](=O)[O-])c2c1[N+](=O)[O-]
Temperature: 0 °C
Yield: 55.1 %

Procedure:
2-Ethoxalylamino-1-nitronaphthalene (11.5 g, 0.04 mol) was dissolved in 80 ml of sulfuric acid (d 1.84)by portionwise addition, with vigorous stirring on an ice-bath. Nitric acid (1.66 ml, 0.04 mol, d 1.52) in 20 ml of sulfuric acid (d 1.84) was added dropwise during 1 h at 0° C., and the mixture was stirred at this temperature for a further hour. The mixture was cautiously poured into 600 ml of ice/water with vigorous stirring. The yellow solid was collected, washed with water, and boiled with 300 ml of ethanol. The hot suspension was filtered and the undissolved residue was washed with 200 ml of ether to yield 7.35 g (55%) of the title compound, m.p. 232.7-233.4° C. (acetic acid),1H-NMR (DMSO-d6) 1.33 (t,J=7Hz,3H,CH3), 4.34 (q,J=7Hz,2H,CH2), 7.7-8.6 (m,5H,ArH), 11.12 (s,1H,NH).
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([CH:10]=[C:11]([N+:13]([O-])=O)[CH:12]=1)[C:7]([NH2:9])=[O:8])([O-])=O.[H][H]>[Pd].C(OCC)(=O)C.C(O)C>[NH2:1][C:4]1[CH:5]=[C:6]([CH:10]=[C:11]([NH2:13])[CH:12]=1)[C:7]([NH2:9])=[O:8]
Reactant: [H][H]
Reactant: NC(=O)c1cc([N+](=O)[O-])cc([N+](=O)[O-])c1
Agent: [Pd]
Solvent: CCO
Solvent: CCOC(C)=O
Product: NC(=O)c1cc(N)cc(N)c1

Procedure:
A solution of 20.5 gm. (0.097 mole) of 3,5-dinitrobenzamide in 450 ml. of an ethyl acetate-ethanol mixture (2:1) is hydrogenated at 3 atmospheres of hydrogen using 1 gm. of 10% palladium on charcoal as catalyst. When absorption of hydrogen is complete, the catalyst is removed by filtration and the filtrate is concentrated to dryness under reduced pressure and the residue recrystallized from water. There is obtained 11.65 gm. (79%) of long yellow needles melting at 108°-9° .
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([NH:11][C:12]3[N:17]=[C:16]([O:18][CH2:19][C:20]([F:23])([F:22])[F:21])[N:15]=[C:14]([NH:24][C:25]4[CH:33]=[CH:32][C:28]([C:29](O)=[O:30])=[C:27]([F:34])[CH:26]=4)[N:13]=3)[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[NH2:57][CH2:58][C:59]([CH3:68])([CH3:67])[CH2:60][NH:61][C:62](=[O:66])[C:63]([NH2:65])=[O:64].CCN(C(C)C)C(C)C>CN(C=O)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([NH:11][C:12]3[N:17]=[C:16]([O:18][CH2:19][C:20]([F:22])([F:21])[F:23])[N:15]=[C:14]([NH:24][C:25]4[CH:33]=[CH:32][C:28]([C:29]([NH:57][CH2:58][C:59]([CH3:68])([CH3:67])[CH2:60][NH:61][C:62](=[O:66])[C:63]([NH2:65])=[O:64])=[O:30])=[C:27]([F:34])[CH:26]=4)[N:13]=3)[CH2:10][CH2:9]2)=[CH:4][CH:3]=1
Reactant: CC(C)(CN)CNC(=O)C(N)=O
Reactant: O=C(O)c1ccc(Nc2nc(NC3(c4ccc(Cl)cc4)CC3)nc(OCC(F)(F)F)n2)cc1F
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[B-](F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: CC(C)(CNC(=O)C(N)=O)CNC(=O)c1ccc(Nc2nc(NC3(c4ccc(Cl)cc4)CC3)nc(OCC(F)(F)F)n2)cc1F
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a solution of 4-((4-((1-(4-chlorophenyl)cyclopropyl)amino)-6-(2,2,2-trifluoroethoxy)-1,3,5-triazin-2-yl)amino)-2-fluorobenzoic acid (10 mg) and TBTU (7.74 mg) in DMF (1 mL) was added N1-(3-amino-2,2-dimethylpropyl)oxalamide (4.18 mg) and DIPEA (0.018 mL). The mixture was stirred at room temperature for 2 hours. The product was isolated by using preparative HPLC system.
Reaction SMILES: [C:1]([N:5]([C:7](=[O:16])[C:8]1[CH:13]=[C:12]([CH3:14])[CH:11]=[C:10]([CH3:15])[CH:9]=1)[NH2:6])([CH3:4])([CH3:3])[CH3:2].[F:17][C:18]1[CH:26]=[C:25]([CH2:27][CH3:28])[CH:24]=[CH:23][C:19]=1[C:20](Cl)=[O:21].C(=O)([O-])[O-].[K+].[K+]>C(Cl)Cl.O>[C:1]([N:5]([C:7](=[O:16])[C:8]1[CH:9]=[C:10]([CH3:15])[CH:11]=[C:12]([CH3:14])[CH:13]=1)[NH:6][C:20](=[O:21])[C:19]1[CH:23]=[CH:24][C:25]([CH2:27][CH3:28])=[CH:26][C:18]=1[F:17])([CH3:4])([CH3:3])[CH3:2]
Reactant: Cc1cc(C)cc(C(=O)N(N)C(C)(C)C)c1
Reactant: CCc1ccc(C(=O)Cl)c(F)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: ClCCl
Solvent: O
Product: CCc1ccc(C(=O)NN(C(=O)c2cc(C)cc(C)c2)C(C)(C)C)c(F)c1
Reaction time: 8 h

Procedure:
0.150 g of 3,5-dimethyl-benzoic acid N-tert-butyl-hydrazide (1 eq, 0.68 mmol) and 0.110 mL (1.2 eq, 0.77 mmol) of 2-fluoro-4-ethyl benzoyl chloride were weighed into a 1 oz. vial. A small stirbar was added followed by 2 mL of methylene chloride. The mixture was stirred until the hydrazone dissolved. The stirring was stopped and 2 mL of a 1 M potassium carbonate (K2CO3) solution was added. The mixture was allowed to stir overnight. At the end of this period, 1 mL of water and 1 mL of methylene chloride were added. The aqueous phase was removed and the organic phase was washed twice with 1 M potassium carbonate solution. The organic phase was removed and dried over magnesium sulfate. The organic phase was filtered thru a pad of basic alumina and the solvent removed. The product, 3,5-dimethylbenzoic acid N-tert-butyl-N′-(2-fluoro-4-ethylbenzoyl)-hydrazide, was purified by trituration with 1:1 ether: hexane. 1H NMR (300 MHz, CDCl3) δ (ppm): 7.7 (m, 2H), 7.6 (t, 1H), 7.0 (m, 3H), 2.6 (q, 2H), 2.3 (s, 3H), 2.1 (s, 6H), 1.5 (s, 9H), 1.1 (t, 3H).
Reaction SMILES: [NH2:1][C:2]1[C:7]([NH2:8])=[CH:6][CH:5]=[CH:4][C:3]=1[N+:9]([O-])=O.[C:12]1([C:18]([C:20]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=O)=O)[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C(O)(=O)C>CO>[C:12]1([C:18]2[C:20]([C:22]3[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=3)=[N:1][C:2]3[C:3](=[CH:4][CH:5]=[CH:6][C:7]=3[NH2:8])[N:9]=2)[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1
Reactant: Nc1cccc([N+](=O)[O-])c1N
Reactant: O=C(C(=O)c1ccccc1)c1ccccc1
Solvent: CC(=O)O
Solvent: CO
Product: Nc1cccc2nc(-c3ccccc3)c(-c3ccccc3)nc12

Procedure:
1.53 g (10 mmol) of 2,3-diaminonitrobenzene and 2.00 g (9.6 mmol) of benzil were placed in four-necked flask, to which 30 g of a solvent of acetic acid and methanol at a mixing ratio of 1:1 was added for dissolution. Subsequently, the mixture was reacted at a reaction temperature of 70° C. for 2 hours. After the reaction, the solvent was removed and the resulting product was extracted with a silica gel column (ethyl acetate:hexane=1:1).
Reaction SMILES: [NH2:1][CH2:2][C:3]([OH:5])=[O:4].[OH-].[Na+].[C:8](Cl)(=[O:20])[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH3:19].Cl>CCOCC>[C:8]([NH:1][CH2:2][C:3]([OH:5])=[O:4])(=[O:20])[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH3:19]
Reactant: CCCCCCCCCCCC(=O)Cl
Reactant: NCC(=O)O
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCOCC
Product: CCCCCCCCCCCC(=O)NCC(=O)O
Reaction time: 1 h
Yield: 84.7 %

Procedure:
To a solution of glycine in a 1 N-sodium hydroxide, an ether solution of n-dodecanoyl chloride and a 1 N-aqueous solution of sodium hydroxide were dropped simultaneously and the mixture was stirred for 1 hour. The reaction mixture was then neutralized with hydrochloric acid and ether was removed from the solution. N-n-dodecanoylglycine was obtained from the remaining reactant after the purification by column chromatography with the yield of 84.7%. The melting point of the product was 115.5° to 116.7° C.
Reaction SMILES: NC(N)=[S:3].[Cl:5][C:6]1[CH:23]=[CH:22][C:9]([CH2:10][N:11]2[CH2:17][CH2:16][CH2:15][N:14]([CH2:18][CH2:19][CH2:20]Cl)[CH2:13][CH2:12]2)=[CH:8][CH:7]=1.C(O)C.[OH-].[Na+]>O>[Cl:5][C:6]1[CH:23]=[CH:22][C:9]([CH2:10][N:11]2[CH2:17][CH2:16][CH2:15][N:14]([CH2:18][CH2:19][CH2:20][SH:3])[CH2:13][CH2:12]2)=[CH:8][CH:7]=1
Reactant: NC(N)=S
Reactant: ClCCCN1CCCN(Cc2ccc(Cl)cc2)CC1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: SCCCN1CCCN(Cc2ccc(Cl)cc2)CC1
Temperature: 25 °C
Reaction time: 8 h
Yield: 39.1 %

Procedure:
4.1 g of thiourea were added to a mixture of 8.0 g of 1-(4-chlorobenzyl)-4-(3-chloropropyl)homopiperazine and 100 ml of reagent ethanol. The mixture was refluxed for 6 hours and then stirred overnight at room temperature. A solution of 5.0 g of sodium hydroxide in 30 ml of water was added, and the resulting solution was refluxed for 4 hours. The ethanol was removed in vacuo, and water was added to the residue. The product was extracted with methylene chloride, and the extract was dried (sodium sulfate) and concentrated to give 3.1 g (39% of theory) of 3-[4-(4-chlorobenzyl)homopiperazin-1-yl]propanethiol as a yellow oil.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][CH2:10][OH:11])=[CH:4][CH:3]=1.ClCCl.[CH3:15][S:16](Cl)(=[O:18])=[O:17]>C(N(CC)CC)C>[CH3:15][S:16]([O:11][CH2:10][CH2:9][CH2:8][C:5]1[CH:4]=[CH:3][C:2]([Br:1])=[CH:7][CH:6]=1)(=[O:18])=[O:17]
Reactant: CS(=O)(=O)Cl
Reactant: OCCCc1ccc(Br)cc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CS(=O)(=O)OCCCc1ccc(Br)cc1
Temperature: 0 °C
Reaction time: 1 h
Yield: 91.5 %

Procedure:
3-(4-Bromophenyl)propan-1-ol (335 g) and dichloromethane (2.5 L) was charged into Reactor 1. Reactor 1 was adjusted to −10 to 0° C. Triethylamine (205 g) was charged into Reactor 1. Methanesulphonyl chloride (272.7 g) was added dropwise into Reactor 1 maintaining contents at <0° C. Reactor 1 was stirred at −5 to 5° C. for 1 h then analysed for reaction completion. The organic layer was washed with water (1 L) and saturated NaCl solution (1 L). The organic layer was evaporated down to dryness to give 3-(4-bromophenyl)propyl methanesulfonate (418 g).