Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[CH3:11])[C:5]([OH:7])=O.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.CCN(C(C)C)C(C)C.[CH3:43][NH:44][C@@H:45]([CH2:52][CH2:53][CH3:54])[CH2:46][N:47]1[CH2:50][CH:49]([OH:51])[CH2:48]1>C(Cl)Cl>[OH:51][CH:49]1[CH2:48][N:47]([CH2:46][C@@H:45]([N:44]([CH3:43])[C:5](=[O:7])[C:4]2[CH:8]=[CH:9][C:10]([CH3:11])=[C:2]([CH3:1])[CH:3]=2)[CH2:52][CH2:53][CH3:54])[CH2:50]1
Reactant: Cc1ccc(C(=O)O)cc1C
Reactant: CCC[C@@H](CN1CC(O)C1)NC
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[B-](F)(F)F
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CCC[C@@H](CN1CC(O)C1)N(C)C(=O)c1ccc(C)c(C)c1
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 27.2 %

Procedure:
3,4-Dimethylbenzoic acid (0.174 g, 1.16 mmol), TBTU (0.373 g, 1.16 mmol) and DIPEA (0.303 mL, 1.74 mmol) was stirred in DCM (2 mL) for 40 min before (S)-1-(2-(methylamino)pentyl)azetidin-3-ol (Compound J4) (0.1 g, 0.58 mmol) was added. The resultant mixture was stirred at rt overnight. The solvent was removed under reduced pressure and the residue dissolved in a mixture of MeOH (3 mL) and NaOH (aq. 1 mL, 1M). The resultant mixture was stirred at rt for 90 min before the MeOH was removed on a vacuum centrifuge. The crude product was extracted with DCM and concentrated under reduced pressure. To the residue was DMSO (1 mL), DCM (3 mL) and KOH (1M solution, 3 mL) added. The organic phase was filtered through a phase separator and concentrated under reduced pressure. The residue was purified by preparative HPLC. The product containing fractions was concentrated, water (5 mL) and DCM (5 mL) was added and the pH was adjusted to 12 using KOH (1M solution). The organic layer was filtered through a phase separator and the solvent was removed under reduced pressure to give the title compound (48 mg, 27%). Mixture of rotamers: (600 MHz, DMSO-d6) δ 0.69-0.78, 0.85-0.93, 0.94-1.06, 1.08-1.50, 2.19-2.28, 2.32-2.41, 2.44-2.56, 2.56-2.65, 2.66-2.76, 3.27-3.38, 3.43-3.55, 4.03-4.20, 4.44-4.52, 5.17-5.26, 6.97-7.21. Total no of protons: 28. HRMS (M+H)+: calculated 305.2229. found 305.2214.
Reaction SMILES: [CH3:1][C:2]1([CH3:15])[CH2:6][CH2:5][C:4]([CH3:7])=[C:3]1[CH:8]=[CH:9][C:10](=[O:14])[CH2:11][CH2:12][CH3:13].[OH:16]C1(C)CC(O)CC(C)(C)C1C=CC(O)C>>[OH:16][C:4]1([CH3:7])[CH2:5][CH2:6][C:2]([CH3:1])([CH3:15])[CH:3]1[CH:8]=[CH:9][CH:10]([OH:14])[CH2:11][CH2:12][CH3:13]
Reactant: CC(O)C=CC1C(C)(C)CC(O)CC1(C)O
Reactant: CCCC(=O)C=CC1=C(C)CCC1(C)C
Product: CCCC(O)C=CC1C(C)(C)CCC1(C)O

Procedure:
The entitled compound was obtained from 1-(2,2,5-trimethylcyclopent-5-enyl)hex-1-en-3-one in the same manner as in Example 1-(4), (5), and (6).
Reaction SMILES: [C:1]1([Si:7]([CH3:16])([CH3:15])[CH:8]2[CH2:13][CH2:12][C:11](=O)[CH2:10][CH2:9]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:17]([NH:19][C:20]([NH2:22])=[NH:21])#[N:18]>C(OCCOCCO)C>[NH2:22][C:20]1[N:19]=[C:17]([NH2:18])[C:12]2[CH2:13][CH:8]([Si:7]([C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)([CH3:16])[CH3:15])[CH2:9][CH2:10][C:11]=2[N:21]=1
Reactant: N#CNC(=N)N
Reactant: C[Si](C)(c1ccccc1)C1CCC(=O)CC1
Solvent: CCOCCOCCO
Product: C[Si](C)(c1ccccc1)C1CCc2nc(N)nc(N)c2C1

Procedure:
This compound is prepared in a manner analogous to that of Example 1, using 3.0 grams (0.013 mole) of 4-(phenyldimethylsilyl)cyclohexanone and 1.2 grams (0.014 mole) of cyanoguanidine in 2-(2-ethoxyethoxy)ethanol, yielding 2,4-diamino-6-(phenyldimethylsilyl)-5,6,7,8-tetrahydroquinazoline.
Reaction SMILES: [Br:1][CH:2]([CH3:6])[C:3](Cl)=[O:4].[CH3:7][N:8]1[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[CH2:12][CH2:11][C:9]1=[O:10].[Al+3].[Cl-].[Cl-].[Cl-]>C(Cl)(Cl)Cl>[Br:1][CH:2]([CH3:6])[C:3]([C:15]1[CH:14]=[C:13]2[C:18](=[CH:17][CH:16]=1)[N:8]([CH3:7])[C:9](=[O:10])[CH2:11][CH2:12]2)=[O:4]
Reactant: CC(Br)C(=O)Cl
Reactant: CN1C(=O)CCc2ccccc21
Agent: [Al+3]
Agent: [Cl-]
Solvent: ClC(Cl)Cl
Product: CC(Br)C(=O)c1ccc2c(c1)CCC(=O)N2C
Temperature: 25 °C

Procedure:
2-Bromopropionyl chloride (41.1 g) is added dropwise to a suspension of the N-methyl product obtained in Step 1. above (18.6 g) and AlCl3 (37.4 g) in chloroform (350 ml). The stirred reaction mixture is refluxed for 4 hours, cooled to RT and stirred with an ice/water mixture for 45 minutes. The reaction mixture is separated, extracted with methylene chloride and the combined extracts are washed with H2O, 5% aq. bicarbonate, H2O, dried, filtered and concentrated in vacuo, yielding a viscous oil, which is crystallized from ethyl acetate affording the desired product, M.P.=86°-88° C.
Reaction SMILES: CS(O[CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH:15]=[CH2:16])(=O)=O.[NH2:17][C:18]1[CH:28]=[CH:27][C:21]([C:22]([O:24][CH2:25][CH3:26])=[O:23])=[CH:20][CH:19]=1.C(O)C>CN(C)P(N(C)C)(N(C)C)=O.C(O)C.O>[CH2:6]([NH:17][C:18]1[CH:19]=[CH:20][C:21]([C:22]([O:24][CH2:25][CH3:26])=[O:23])=[CH:27][CH:28]=1)[CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH:15]=[CH2:16]
Reactant: CCOC(=O)c1ccc(N)cc1
Reactant: C=CCCCCCCCCCOS(C)(=O)=O
Solvent: O
Solvent: CN(C)P(=O)(N(C)C)N(C)C
Solvent: CCO
Product: C=CCCCCCCCCCNc1ccc(C(=O)OCC)cc1

Procedure:
A solution of 14.0 g. of 1-methanesulfonyloxy-10-undecene and 19.8 g. of ethyl p-aminobenzoate in hexamethylphosphoramide is heated at 120° C. for 20 hours. After cooling the reaction mixture is diluted with ethanol:water (1:1) (30 ml.) and chilled. More ethanol is added and the solid material is collected. This solid is recrystallized from ethanol to yield ethyl 4-(10-undecenylamino)benzoate as a white solid.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([I:8])=[CH:4][C:3]=1[N:9]1[CH:14]=[C:13]([O:15][CH3:16])[C:12](=[O:17])[C:11]([C:18](N(OC)C)=[O:19])=[N:10]1.[CH3:24][Mg+].[Br-]>C1COCC1>[C:18]([C:11]1[C:12](=[O:17])[C:13]([O:15][CH3:16])=[CH:14][N:9]([C:3]2[CH:4]=[C:5]([I:8])[CH:6]=[CH:7][C:2]=2[F:1])[N:10]=1)(=[O:19])[CH3:24]
Reactant: COc1cn(-c2cc(I)ccc2F)nc(C(=O)N(C)OC)c1=O
Reactant: C[Mg+]
Agent: [Br-]
Solvent: C1CCOC1
Product: COc1cn(-c2cc(I)ccc2F)nc(C(C)=O)c1=O
Temperature: -78 °C
Reaction time: 2 h
Yield: 92.2 %

Procedure:
To a mixture of 1-(2-fluoro-5-iodophenyl)-N,5-dimethoxy-N-methyl-4-oxo-1,4-dihydropyridazine-3-carboxamide (4.33 g, 10.0 mmol) in THF (1.0 L) was added MeMgBr (1.0 M in THF, 20.0 mL, 20.0 mmol) at −78° C. under N2. The mixture was stirred at −78° C. for 2 h. The reaction was quenched with saturated NH4Cl aqueous solution at −78° C. The mixture was diluted with saturated NaHCO3 aqueous solution, extracted with EtOAc, dried over Na2SO4, filtered, concentrated in vacuo, purified by column chromatography on silica gel (hexane/EtOAc=50/50 to 0/100 and EtOAc/MeOH=100/0 to 0/100) and triturated with EtOAc/hexane to yield the title compound (3.58 g, 92% yield) as a pale yellow solid: 1H NMR (DMSO-d6, 300 MHz): δ ppm 2.50 (3H, s), 3.80 (3H, s), 7.38 (1H, dd, J=11.0, 8.7 Hz), 7.95 (1H, ddd, J=8.7, 4.5, 2.3 Hz), 8.15 (1H, dd, J=7.2, 2.3 Hz), 8.52 (1H, d, J=1.5 Hz).
Reaction SMILES: [C:1]1([PH:7][C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.FC(F)(F)S(O[C:20]1[CH:29]=[CH:28][C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[C:21]=1[C:30]([O:32][CH3:33])=[O:31])(=O)=O.C(N(CC)CC)C>CN(C=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:8]1([P:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[C:20]2[CH:29]=[CH:28][C:27]3[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=3)[C:21]=2[C:30]([O:32][CH3:33])=[O:31])[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1
Reactant: c1ccc(Pc2ccccc2)cc1
Reactant: COC(=O)c1c(OS(=O)(=O)C(F)(F)F)ccc2ccccc12
Agent: [Pd+2]
Agent: CC(=O)[O-]
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: COC(=O)c1c(P(c2ccccc2)c2ccccc2)ccc2ccccc12

Procedure:
Diphenylphosphine (0.72 mL, 4.14 mmol, 1 eq) was added to a stirred solution of methyl 2-trifluoromethanesulfonyloxy-1-naphthoate (1.384 g, 4.14 mmol, 1 eq), triethylamine (0.64 mL, 4.59 mmol, 1.1 eq) and palladium acetate (0.005 g, 0.02 mmol, 0.005 eq) in degassed DMF (10 mL) instantly giving a red coloration. The solution was heated at reflux under nitrogen for 17 hours. The blood-red solution was allowed to cool and an aliquot taken for NMR analysis.
Reaction SMILES: [NH:1]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[C@H:2]([C:7](O)=[O:8])[C@H:3]([CH2:5][CH3:6])[CH3:4].CN1CCOCC1.ClC(OCC(C)C)=O>COCCOC>[C:10]([NH:1][C@H:2]([CH2:7][OH:8])[C@H:3]([CH2:5][CH3:6])[CH3:4])([O:12][C:13]([CH3:15])([CH3:16])[CH3:14])=[O:11]
Reactant: CC[C@H](C)[C@H](NC(=O)OC(C)(C)C)C(=O)O
Agent: CC(C)COC(=O)Cl
Solvent: COCCOC
Solvent: CN1CCOCC1
Product: CC[C@H](C)[C@@H](CO)NC(=O)OC(C)(C)C
Reaction time: 0.02 h
Yield: 92.2 %

Procedure:
In 5 ml of 1,2-dimethoxyethane (DME), 1.201 g of Boc-Ile-OH.1/2H2O was dissolved and 550 μl of N-methylmorpholine and 650 μl of isobutyl chloroformate were successively added dropwise at −15° C. After stirring for 1 min, the formed N-methylmorpholine hydrochloride was filtered off and washed twice with 2.5 ml each of DME. The filtrate and washings were combined and 284 mg of sodium borohydride in 2.5 ml of water was added in one portion. After 30 sec, 125 ml of water was added and the mixture was extracted with 25 ml of ethyl acetate and dried over anhydrous sodium sulfate. The dried solution was evaporated under reduced pressure to give 1.040 g of the title compound.
Reaction SMILES: [CH2:1](B1OC(C)(C)C(C)(C)O1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl[C:18]1[CH:19]=[C:20]([C:33]2[N:38]=[C:37]([CH3:39])[N:36]=[C:35]([N:40]([CH2:50][C:51]3[CH:56]=[CH:55][C:54]([O:57][CH3:58])=[CH:53][CH:52]=3)[CH2:41][C:42]3[CH:47]=[CH:46][C:45]([O:48][CH3:49])=[CH:44][CH:43]=3)[N:34]=2)[C:21]([NH:24][C:25]2[CH:26]=[N:27][C:28]([O:31][CH3:32])=[CH:29][CH:30]=2)=[N:22][CH:23]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(CCC)=CC(CCC)=CC=2CCC)CCCCC1.C(=O)([O-])[O-].[Na+].[Na+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O.O1CCOCC1>[CH2:1]([C:18]1[CH:19]=[C:20]([C:33]2[N:38]=[C:37]([CH3:39])[N:36]=[C:35]([N:40]([CH2:50][C:51]3[CH:56]=[CH:55][C:54]([O:57][CH3:58])=[CH:53][CH:52]=3)[CH2:41][C:42]3[CH:47]=[CH:46][C:45]([O:48][CH3:49])=[CH:44][CH:43]=3)[N:34]=2)[C:21]([NH:24][C:25]2[CH:26]=[N:27][C:28]([O:31][CH3:32])=[CH:29][CH:30]=2)=[N:22][CH:23]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CC1(C)OB(Cc2ccccc2)OC1(C)C
Reactant: COc1ccc(CN(Cc2ccc(OC)cc2)c2nc(C)nc(-c3cc(Cl)cnc3Nc3ccc(OC)nc3)n2)cc1
Agent: [Pd]
Agent: CCCc1cc(CCC)c(-c2ccccc2P(C2CCCCC2)C2CCCCC2)c(CCC)c1
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Solvent: O
Solvent: C1COCCO1
Product: COc1ccc(CN(Cc2ccc(OC)cc2)c2nc(C)nc(-c3cc(Cc4ccccc4)cnc3Nc3ccc(OC)nc3)n2)cc1
Temperature: 140 °C
Yield: 62.8 %

Procedure:
A mixture of 2-benzyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (Frontier Scientific Inc., 90 mg, 0.411 mmol), 4-(5-chloro-2-(6-methoxypyridin-3-ylamino)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (160 mg, 0.274 mmol), Pd2dba3 (12.54 mg, 0.014 mmol), 2-(dicyclohexylphosphino)-2′,4′,6′,-tri-1-propyl-1,1′-biphenyl (X-Phos, 13.06 mg, 0.027 mmol) (Strem Co.) was purged with argon and then treated with dioxane (2.50 mL), water (0.25 mL) and sodium carbonate (72.6 mg, 0.685 mmol) and heated under a microwave irradiation at 140° C. for 30 min. The mixture was filtered through a short plug of Celite® (diatomaceous earth), washed with EtOAc (×3), and concentrated. The crude product was adsorbed onto a plug of silica gel and chromatographed through a Redi-Sep pre-packed silica gel column (pure hexanes to 30% EtOAc in hexanes) to give 4-(5-benzyl-2-(6-methoxypyridin-3-ylamino)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (110 mg, 62.8%) as a yellow syrup. m/z (ESI, +ve ion) 640.0 (M+H)+.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[C:4]([N+:9]([O-])=O)[CH:3]=1.N1CCC[CH2:13]1>CN(C=O)C.C(OCC)C.[Zn]>[Br:1][C:2]1[CH:3]=[C:4]2[C:5]([CH:8]=[CH:13][NH:9]2)=[CH:6][CH:7]=1
Reactant: Cc1ccc(Br)cc1[N+](=O)[O-]
Reactant: C1CCNC1
Agent: [Zn]
Solvent: CN(C)C=O
Solvent: CCOCC
Product: Brc1ccc2cc[nH]c2c1
Temperature: 110 °C

Procedure:
To a solution of 4-bromo-2-nitrotoluene (4.3 g., 20 mmol.) in DMF (40 mL.) was added DMF dimethylacetal (7.15 g., 60 mmol.) and pyrrolidine (1.4 g., 20 mmol.). The solution was heated to 110° C. for 4 hr. then cooled to rt. and diluted with ethyl ether. The mixture was washed 3× with water, dried with Na2SO4, filtered and the solvent evaporated. The residue was dissolved in 80% aqueous acetic acid (125 mL.) and heated to 75° C. Zinc dust (9.75 g., 150 mmol.) was added gradually over 20 min. The reaction mixture was heated to 85° C. for 2 hr. then cooled to ~35° C. and filtered to remove unreacted zinc. The filtrate was diluted with ethyl ether, washed 3× with water then with saturated aqueous NaHCO3. The solution was dried with Na2SO4, filtered and concentrated in vacuo to ~30 mL. then diluted with hexanes and filtered. The filtrate was concentrated to an off-white solid which was dissolved in hexane, filtered, and concentrated to give 1.65 g. of the title compound as a light green solid.
Reaction SMILES: ClC1C=CC=C(C(OO)=[O:9])C=1.[CH3:12][O:13][CH2:14][O:15][CH2:16][C:17]([CH3:19])=[CH2:18].C(=O)([O-])O.[Na+].O>C(Cl)Cl>[CH3:12][O:13][CH2:14][O:15][CH2:16][C:17]1([CH3:19])[CH2:18][O:9]1
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: C=C(C)COCOC
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: O
Product: COCOCC1(C)CO1
Temperature: 25 °C
Reaction time: 6 h
Yield: 61.3 %

Procedure:
m-Chloroperbenzoic acid (22.7 g, 92 mmol) was gradually added to a solution of 3-methoxymethoxy-2-methyl-1-propene (9.7 g, 84 mmol) prepared in Reference Example 176 in methylene chloride (200 ml) while cooling in an ice-bath and the mixture was stirred at room temperature for 6 hours. Sodium hydrogencarbonate (14.1 g, 168 mmol), water and methylene chloride were added to the reaction mixture, which was stirred for a while. The organic layer was separated, washed with sodium hydrogencarbonate aqueous solution, sodium thiosulfate aqueous solution and then sodium hydrogencarbonate aqueous solution, and dried over magnesium sulfate. After filtration, the filtrate was concentrated under reduced pressure to afford 2-methoxymethoxymethyl-2-methyloxirane (6.8 g, yield 62%) as a green-colored oil.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][C:12]2[C:15]([C:20]3[NH:21][N:22]=[N:23][C:24]=3[C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)=[C:16]([Cl:19])[CH:17]=[CH:18][C:11]=2[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:31](=O)([O-])[O-].[K+].[K+].IC>CC(C)=O>[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][C:12]2[C:15]([C:20]3[C:24]([C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)=[N:23][N:22]([CH3:31])[N:21]=3)=[C:16]([Cl:19])[CH:17]=[CH:18][C:11]=2[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: O=C([O-])[O-]
Reactant: CC(C)(C)OC(=O)N1CCc2ccc(Cl)c(-c3[nH]nnc3-c3ccccc3)c2CC1
Agent: [K+]
Solvent: CI
Solvent: CC(C)=O
Product: Cn1nc(-c2ccccc2)c(-c2c(Cl)ccc3c2CCN(C(=O)OC(C)(C)C)CC3)n1

Procedure:
Dissolve 3-tert-butoxycarbonyl-7-chloro-6-(5-phenyl-3H-[1,2,3]triazol-4-yl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine (24 mg, 0.06 mmol) in acetone (1.4 mL). Add potassium carbonate (41 mg, 0.3 mmol) and iodomethane (7.4 μL, 0.12 mmol) and stir for 16 h at room temperature. Filter the mixture through a fritted glass funnel and evaporate the filtrate. Purify the crude mixture by chromatography on silica gel to obtain the desired intermediate as the first of the three methylation isomers (7.8 mg, 25%).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH:10]2[CH2:14][NH:13][C:12](=[O:15])[CH2:11]2)[CH:5]=[CH:6][C:7]=1[O:8][CH3:9].[H-].[Na+].[Si:18](Cl)([C:21]([CH3:24])([CH3:23])[CH3:22])([CH3:20])[CH3:19]>CN(C)C=O>[Br:1][C:2]1[CH:3]=[C:4]([CH:10]2[CH2:14][N:13]([Si:18]([C:21]([CH3:24])([CH3:23])[CH3:22])([CH3:20])[CH3:19])[C:12](=[O:15])[CH2:11]2)[CH:5]=[CH:6][C:7]=1[O:8][CH3:9]
Reactant: CC(C)(C)[Si](C)(C)Cl
Reactant: COc1ccc(C2CNC(=O)C2)cc1Br
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COc1ccc(C2CC(=O)N([Si](C)(C)C(C)(C)C)C2)cc1Br
Temperature: 0 °C
Reaction time: 0.33 h
Yield: 54.6 %

Procedure:
Under nitrogen, 540 mg (2 mmol) of 4-(3-bromo-4-methoxyphenyl)pyrrolidin-2-one in 10 ml of dimethylformamide is combined with 60 mg (2 mmol) of sodium hydride. After 20 minutes of stirring, after cooling to 0° C., 300 mg (2 mmol) of tert-butyldimethylsilyl chloride in 5 ml of dimethylformamide is added dropwise and the mixture stirred at 0° C. for 30 minutes as well as at room temperature for 30 minutes. After concentration, the mixture is distributed in ethyl acetate/water. The ethyl acetate phase is dried, filtered and concentrated and the residue is chromatographed over silica gel with methylene chloride:ethanol=10:1 as the eluent, thus obtaining 420 mg of 4-(3-bromo-4-methoxyphenyl)-1-tert-butyldimethylsilylpyrrolidin-2-one, mp 150°-152° C.
Reaction SMILES: [CH2:1]([Cl:4])[CH:2]=[CH2:3].[CH2:5]([SiH:8]([O:11][CH3:12])[O:9][CH3:10])[CH:6]=[CH2:7]>[H+].[H+].Cl[Pt-2](Cl)(Cl)(Cl)(Cl)Cl>[Cl:4][CH2:1][CH2:2][CH2:3][Si:8]([O:11][CH3:12])([O:9][CH3:10])[CH2:5][CH:6]=[CH2:7]
Reactant: C=CC[SiH](OC)OC
Reactant: C=CCCl
Agent: Cl[Pt-2](Cl)(Cl)(Cl)(Cl)Cl
Agent: [H+]
Product: C=CC[Si](CCCCl)(OC)OC
Yield: 76643.8 %

Procedure:
Using the same apparatus and procedure described in EXAMPLE 1, 7.7 g (0.1 mol) of allylchloride and 60 μl of 1% chloroplatinic acid catalyst were added to the flask. Through the dropping funnel was added dropwise 6.6 g (0.05 mmol) of allyldimethoxysilane for 30 min. while refluxing. After confirming by gas chromatography to complete the reaction, the product was fractionally distilled under vacuum (59°-62° C./0.5 torr) to give 8.0 g (81%) of 7-chloro-4,4-dimethoxy-4-sila-1-heptene.
Reaction SMILES: Br[C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=[C:4]([F:11])[C:3]=1[NH2:12].[CH3:13][C:14]([CH3:18])([CH3:17])[C:15]#[CH:16]>CCN(CC)CC.[Cu]I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:13][C:14]([CH3:18])([CH3:17])[C:15]#[C:16][C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=[C:4]([F:11])[C:3]=1[NH2:12]
Reactant: Nc1c(F)cc([N+](=O)[O-])cc1Br
Reactant: C#CC(C)(C)C
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Cu]I
Solvent: CCN(CC)CC
Product: CC(C)(C)C#Cc1cc([N+](=O)[O-])cc(F)c1N
Temperature: 80 °C
Reaction time: 10 h
Yield: 36 %

Procedure:
To a solution of 2-bromo-6-fluoro-4-nitro-phenylamine (11 g, 47 mmol) in dry Et3N (100 mL) was added CuI (445 mg, 5% mol), Pd(PPh3)2Cl2 (550 mg, 5% mol) and 3,3-dimethyl-but-1-yne (9.6 g, 120 mmol) under N2 protection. The mixture was stirred at 80° C. for 10 h. The reaction mixture was filtered, poured into ice (100 g), and extracted with EtOAc (50 mL×3). The combined organic extracts were dried over anhydrous Na2SO4 and evaporated under vacuum to give the crude product, which was purified by column chromatography on silica gel (petroleum ether/ethyl acetate 50:1) to give 2-(3,3-dimethyl-but-1-ynyl)-6-fluoro-4-nitro-phenylamine (4.0 g, 36%). 1H NMR (400 MHz, CDCl3) δ 8.02 (d, J=1.2 Hz, 1H), 7.84 (dd, J=2.4, 10.8 Hz, 1H), 4.85 (brs, 2H), 1.36 (s, 9H).
Reaction SMILES: [N+:1]([C:4]1[CH:10]=[CH:9][CH:8]=[CH:7][C:5]=1[NH2:6])([O-:3])=[O:2].[Br:11]C1C(=O)C(Br)=CC(Br)(Br)C=1>C(Cl)Cl>[Br:11][C:9]1[CH:8]=[CH:7][C:5]([NH2:6])=[C:4]([N+:1]([O-:3])=[O:2])[CH:10]=1
Reactant: Nc1ccccc1[N+](=O)[O-]
Reactant: O=C1C(Br)=CC(Br)(Br)C=C1Br
Solvent: ClCCl
Product: Nc1ccc(Br)cc1[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 1 h
Yield: 94.2 %

Procedure:
A solution of 2-nitroaniline (5 g, 36.2 mmol) in CH2Cl2 (100 ml) was cooled to -10° C., and treated by 90% 2,4,4,6-tetrabromo-2,5-cyclohexadienone (19.8 g, 43.5 mmol) in 5 portions. The mixture was stirred at -10° C.-0° C. for 1 hr. After being warmed to room temperature, the reaction mixture was washed by 2N NaOH (60 ml) and brine (50 ml), dried over Na2SO4 and evaporated. Flash chromatography on silica gel (5% EtOAc/Hexane) gave 7.40 g (94%) of 17 as a yellow solid: mp 109-110 (lit. mp 112°-113° C.); 1H NMR δ8.27 (1H, d, J=2.3), 7.43 (1H, dd, J=8.9, 2.4), 6.73 (1H, d, J=8.8), 6.09 (NH, brs).
Reaction SMILES: C(OC([NH:8][C@H:9]([C:13]([N:15]([CH3:17])[CH3:16])=[O:14])[CH2:10][O:11][CH3:12])=O)(C)(C)C.Cl.C(OCC)(=O)C>C(OCC)(=O)C>[CH3:16][N:15]([CH3:17])[C:13](=[O:14])[C@H:9]([CH2:10][O:11][CH3:12])[NH2:8]
Reactant: COC[C@H](NC(=O)OC(C)(C)C)C(=O)N(C)C
Agent: Cl
Solvent: CCOC(C)=O
Product: COC[C@H](N)C(=O)N(C)C
Temperature: 25 °C
Reaction time: 8 h
Yield: 147.4 %

Procedure:
To a solution of N2-(tert-butoxycarbonyl)-N,N,O-trimethyl-L-serinamide (2.08 g) in ethyl acetate (10 mL) was is added 4N hydrogen chloride/ethyl acetate solution (10 mL) under ice-cooling. The reaction mixture was stirred at room temperature overnight, and the solvent was evaporated under reduced pressure. To a solution of the residue in methanol (20 mL) was added AMBERLYST (registered trademark) A21 (2.0 g) at room temperature. The reaction mixture was stirred at room temperature for 1 hr. The insoluble material was removed by filtration, and the filtrate was concentrated under reduced pressure to give the title compound (1.82 g).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([N+:10]([O-:12])=[O:11])=[C:6]([CH:9]=1)[CH:7]=O.[C:13]([CH2:15][C:16]([NH2:18])=[O:17])#[N:14].C(NCC)C.[O-]CC.[Na+]>C(O)C>[C:13]([C:15](=[CH:7][C:6]1[CH:9]=[C:2]([Cl:1])[CH:3]=[CH:4][C:5]=1[N+:10]([O-:12])=[O:11])[C:16]([NH2:18])=[O:17])#[N:14]
Reactant: O=Cc1cc(Cl)ccc1[N+](=O)[O-]
Reactant: N#CCC(N)=O
Agent: CC[O-]
Agent: [Na+]
Solvent: CCNCC
Solvent: CCO
Product: N#CC(=Cc1cc(Cl)ccc1[N+](=O)[O-])C(N)=O
Reaction time: 2.5 h

Procedure:
A mixture of 5-chloro-2-nitrobenzaldehyde (47.0 g., 0.25 mole), 2-cyanoacetamide (21.0 g., 0.25 mole), diethylamine (0.5 ml.) and ethanol (500 ml) is heated at reflux for one hour. Sodium ethoxide (10 mg.) is added to the clear mixture and refluxing continued for an additional 2.5 hours. It is then cooled and the crystalline product which precipitates recovered by filtration. Yield = 52.3 g. (88%); m.p. of crude = 183°-185° C. It is used without purification in step B.
Reaction SMILES: [NH2:1][C:2]1[N:6]2[N:7]=[C:8](Cl)[C:9]3[CH2:10][CH2:11][CH2:12][CH2:13][C:14]=3[C:5]2=[N:4][N:3]=1.[NH:16]1[CH2:21][CH2:20][O:19][CH2:18][CH2:17]1>>[NH2:1][C:2]1[N:6]2[N:7]=[C:8]([N:16]3[CH2:21][CH2:20][O:19][CH2:18][CH2:17]3)[C:9]3[CH2:10][CH2:11][CH2:12][CH2:13][C:14]=3[C:5]2=[N:4][N:3]=1
Reactant: Nc1nnc2c3c(c(Cl)nn12)CCCC3
Reactant: C1COCCN1
Product: Nc1nnc2c3c(c(N4CCOCC4)nn12)CCCC3

Procedure:
A 22.40 gm (0.100 mole) quantity of 3-amino-6-chloro-7,8,9,10-tetrahydro-1,2,4-triazolo[3,4-a]phthalazine was added to 225 ml of morpholine and the mixture was refluxed for 7 hours. The mixture was then evaporated. A 250 ml volume of water was added to the residue and the mixture was stirred. The resulting solid was filtered and dried, yielding 27.2 gm of 3-amino-6-(4-morpholinyl)-7,8,9,10-tetrahydro-1,2,4triazolo [3,4-a]phthalazine; mp 260-262° C.