Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([O:4][CH2:5][C:6]1[CH2:13][S:12][CH:11]2[N:8]([C:9](=[O:15])[CH:10]2[NH2:14])[C:7]=1[C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])(=[O:3])[CH3:2].C1(N=C=NC2CCCCC2)CCCCC1.[S:38]1[CH2:43][CH2:42][S:41][CH:40]=[C:39]1[CH2:44][C:45](O)=[O:46]>CN(C)C=O>[C:1]([O:4][CH2:5][C:6]1[CH2:13][S:12][CH:11]2[N:8]([C:9](=[O:15])[CH:10]2[NH:14][C:45](=[O:46])[CH2:44][C:39]2[S:38][CH2:43][CH2:42][S:41][CH:40]=2)[C:7]=1[C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])(=[O:3])[CH3:2]
Reactant: O=C(O)CC1=CSCCS1
Reactant: CC(=O)OCC1=C(C(=O)OC(C)(C)C)N2C(=O)C(N)C2SC1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Solvent: CN(C)C=O
Product: CC(=O)OCC1=C(C(=O)OC(C)(C)C)N2C(=O)C(NC(=O)CC3=CSCCS3)C2SC1
Temperature: 20 °C
Reaction time: 5 h
Yield: 62.2 %

Procedure:
3-Acetoxymethyl-7-amino-2(t-butoxycarbonyl)-8-oxo-5-thia-1-aza-bicyclo[4,2,0]oct-2-ene (11.2 g.) and dicyclohexylcarbodiimide (7.8 g.) are added to a solution of (5,6-dihydro-1,4-dithiin-2-yl)acetic acid (6 g.) in dimethylformamide (50 cc.). The reagents are left in contact for 5 hours, with stirring, at a temperature of about 20° C. and then the solid is filtered off. The filtrate is taken up in ethyl acetate (300 cc.) and is washed with an aqueous solution of sodium bicarbonate, N hydrochloric acid and then with water. After drying over sodium sulphate, it is treated with decolourizing charcoal and concentrated to dryness under reduced pressure (20 mm.Hg). A residue (20 g.) is obtained and is chromatographed on silica (330 g.). Elution is effected using a mixture (10 liters) of ethyl acetate and cyclohexane (1-3 by volume), and the eluates are concentrated to dryness under reduced pressure (20 mm.Hg). 3-Acetoxymethyl-2-(t-butoxycarbonyl)-7-[(5,6-dihydro-1,4-dithiin-2 -yl)acetamido]-8-oxo-5-thia-1 -aza-bicyclo-[4,2,0]oct-2-ene (10.3 g.), melting at 80° C., is thus obtained.
Reaction SMILES: C([O:3][C:4](=[O:20])[CH2:5][CH:6]([N:10]1[C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=2[NH:12][C:11]1=[O:19])[CH2:7][CH2:8][CH3:9])C.[Br:21][C:22]1[CH:23]=[CH:24][C:25]([O:30][CH3:31])=[C:26]([CH2:28]O)[CH:27]=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>C1COCC1>[Br:21][C:22]1[CH:23]=[CH:24][C:25]([O:30][CH3:31])=[C:26]([CH:27]=1)[CH2:28][N:12]1[C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[N:10]([CH:6]([CH2:7][CH2:8][CH3:9])[CH2:5][C:4]([OH:3])=[O:20])[C:11]1=[O:19]
Reactant: COc1ccc(Br)cc1CO
Reactant: CCCC(CC(=O)OCC)n1c(=O)[nH]c2ccccc21
Agent: CC(C)OC(=O)/N=N/C(=O)OC(C)C
Solvent: C1CCOC1
Product: CCCC(CC(=O)O)n1c(=O)n(Cc2cc(Br)ccc2OC)c2ccccc21
Temperature: 0 °C
Yield: 98.4 %

Procedure:
3-(2-Oxo-2,3-dihydro-benzoimidazol-1-yl)-hexanoic acid ethyl ester (96.7 mg, 0.35 mmol), prepared as described above, (5-bromo-2-methoxy-phenyl)-methanol (152 mg, 0.7 mmol) and triphenylphosphene (183.6, 0.7 mmol) were combined in a reaction vial and THF (1 mL) was added. The mixture was stirred until complete solution was attained, then cooled to 0° C., and diisopropylazodicarboxylate (0.136 mL, 0.7 mmol) was added dropwise. The reaction mixture was agitated at room temperature overnight, diluted with THF (2 mL) then treated directly with the Amberlyst® resin (3 g, 4 mmol). This reaction mixture was agitated overnight and the resin was then filtered and washed with DMF (2×3 mL) and several portions of methanol. The product was eluted by treating the resin with a 20% solution of formic acid in methanol (5 mL) and washing with methanol (3 mL). The combined eluant and final wash was evaporated to provide the title compound (154 mg, 99%). LCMS (ESMS): m/z 447/9 (M+H+).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][N:6]=[C:5]2[NH:12][C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([Br:19])[CH:14]=1.[C:20](Cl)(=[O:23])[CH2:21][CH3:22]>C1COCC1>[Br:19][C:15]1[CH:14]=[C:13]([NH:12][C:5]2[C:4]3[C:9](=[CH:10][CH:11]=[C:2]([NH:1][C:20](=[O:23])[CH2:21][CH3:22])[CH:3]=3)[N:8]=[CH:7][N:6]=2)[CH:18]=[CH:17][CH:16]=1
Reactant: CCC(=O)Cl
Reactant: Nc1ccc2ncnc(Nc3cccc(Br)c3)c2c1
Solvent: C1CCOC1
Product: CCC(=O)Nc1ccc2ncnc(Nc3cccc(Br)c3)c2c1
Yield: 52.3 %

Procedure:
To a solution of 6-amino-4-[(3-bromophenyl)amino]quinazoline (157 mg, 0.5 mmol) in dry THF (3 mL) stirred under N2 at 25° C. was added dropwise propionyl chloride (0.05 mL, 0.58 mmol). A yellow solid formed at once. After 45 minutes the solid was collected by filtration and washed with ether and dried. Recrystallized from wet methanol afforded the desired product (97 mg, 47%), mp 265-266° C.
Reaction SMILES: C(N1C=CN=C1)(N1C=CN=C1)=O.[Cl:13][C:14]1[CH:22]=[C:21]([N+:23]([O-:25])=[O:24])[CH:20]=[CH:19][C:15]=1[C:16](O)=[O:17].[BH4-].[Na+].Cl>C1COCC1.O>[Cl:13][C:14]1[CH:22]=[C:21]([N+:23]([O-:25])=[O:24])[CH:20]=[CH:19][C:15]=1[CH2:16][OH:17]
Reactant: O=C(O)c1ccc([N+](=O)[O-])cc1Cl
Agent: Cl
Agent: O=C(n1ccnc1)n1ccnc1
Agent: [BH4-]
Solvent: C1CCOC1
Solvent: O
Product: O=[N+]([O-])c1ccc(CO)c(Cl)c1
Temperature: 35 °C
Reaction time: 1.5 h

Procedure:
35.9 g (0.22 mol) of 1,1′-carbonyldiimidazole is slowly added to a solution of 41.1 g (0.2 mol) of 2-chloro-4-nitrobenzoic acid in 400 mL of THF. The reaction mixture is stirred for 1.5 hours at 35° C. Then the green reaction mixture is cooled down using ice and at maximum 20° C. combined dropwise with a solution of 26.5 g (0.7 mol) of sodium borohydride in 400 mL of water. After 1.5 hours stirring, the reaction mixture is diluted with 200 mL of water and then neutralized with 250 mL of semiconcentrated hydrochloric acid. It is stirred for 1 hour, then extracted twice with ethyl acetate and the organic phase is dried over sodium sulfate. The desiccant is filtered off and the solvent is evaporated down. The residue is crystallized with petroleum ether, suction filtered, and dried at 50° C. in the drying chamber. Yield: 37.66 g (100% of theory); melting point: 62° C.-64° C.; C7H6ClNO3 (M=187.58); calc.: molecular ion peak (M+H)+: 187/189 (Cl); found: molecular ion peak (M+H)+: 187/189 (Cl); Rf value: 0.70 (silica gel, dichloromethane/methanol (90:10)).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([C:9](=O)[CH2:10][C:11]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=O)[CH:5]=[CH:6][C:7]=1[F:8].[NH2:20][C:21]([NH2:23])=[O:22].Cl.ClCCl.CO>O1CCOCC1.C(O)C>[Br:1][C:2]1[CH:3]=[C:4]([C:9]2[CH:10]=[C:11]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[NH:23][C:21](=[O:22])[N:20]=2)[CH:5]=[CH:6][C:7]=1[F:8]
Reactant: O=C(CC(=O)c1ccc(F)c(Br)c1)c1ccccc1
Reactant: NC(N)=O
Agent: Cl
Solvent: ClCCl
Solvent: C1COCCO1
Solvent: CCO
Product: O=c1nc(-c2ccc(F)c(Br)c2)cc(-c2ccccc2)[nH]1
Temperature: 110 °C
Yield: 56.7 %

Procedure:
A solution of 1-(3-bromo-4-fluorophenyl)-3-phenylpropane-1,3-dione (1.08 g, 3.37 mmol), urea (2.03 g, 33.7 mmol) and 4.0 M hydrogen chloride in dioxane (8.4 mL) in ethanol (11 mL) was heated for 48 hours at 110° C. The mixture was then concentrated and taken back into 10 mL 4.0M hydrogen chloride in dioxane. An additional 2.0 g (33 mmol) of urea was added and the solution was again heated for 12 hours at 110° C. The resultant solution was partitioned between 10:1 ethyl acetate/methanol, and saturated sodium bicarbonate (aqueous). The layers were separated and the basic aqueous layer was extracted (2×100 mL ethyl acetate). The combined organic layers were dried (sodium sulfate), filtered and concentrated in vacuo. Column chromatography (silica gel, 95:5 dichloromethane/methanol) gave 0.66 g (57% yield) of 4-(3-bromo-4-fluorophenyl)-6-phenylpyrimidin-2(1H)-one. 1H NMR (400 MHz, DMSO): 8.61 (dd, 1 h), 8.31 (m, 1H), 8.18 (d, 2H), 7.76 (m, 1H), 7.59 (m, 5H).
Reaction SMILES: C[O:2][C:3](=O)[C:4]1[CH:9]=[CH:8][C:7]([C:10]([N:12]2[CH2:17][CH2:16][N:15]([CH:18]([CH3:20])[CH3:19])[CH2:14][CH2:13]2)=[O:11])=[N:6][CH:5]=1.C(O[AlH-](OC(C)(C)C)OC(C)(C)C)(C)(C)C.[Li+]>C1COCC1>[OH:2][CH2:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]([N:12]2[CH2:13][CH2:14][N:15]([CH:18]([CH3:20])[CH3:19])[CH2:16][CH2:17]2)=[O:11])=[N:6][CH:5]=1
Reactant: COC(=O)c1ccc(C(=O)N2CCN(C(C)C)CC2)nc1
Agent: CC(C)(C)O[AlH-](OC(C)(C)C)OC(C)(C)C
Agent: [Li+]
Solvent: C1CCOC1
Product: CC(C)N1CCN(C(=O)c2ccc(CO)cn2)CC1
Reaction time: 18 h
Yield: 60.7 %

Procedure:
A solution of 6-(4-isopropyl-piperazine-1-carbonyl)-nicotinic acid methyl ester (0.500 g, 1.72 mmol) in THF (15 mL) was cooled to −78° C. in a dry ice bath. A solution of lithium tri-tert-butoxyaluminohydride (1 M in THF, 3.44 mL) was then added drop-wise to the reaction mixture. The resulting solution was allowed to come to rt and was stirred for 18 h. The reaction was quenched with satd. aq. potassium sodium tartrate (Rochelle's salt, 15 mL) and extracted with DCM (3×50 mL). The organic layers were combined, dried (Na2SO4), and concentrated to give the title compound (0.275 g, 61%).
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([NH:13][C:14](=[O:24])[C:15]2[CH:20]=[CH:19][C:18]([N:21]([CH3:23])[CH3:22])=[CH:17][CH:16]=2)[CH:7]=[CH:8][C:9]=1[N+:10]([O-])=O)([O-])=O.[CH3:25][N:26]([CH3:41])[C:27]1[CH:32]=[CH:31][C:30]([C:33]2[CH:40]=[CH:39][C:36]([CH:37]=O)=[CH:35][CH:34]=2)=[CH:29][CH:28]=1>>[CH3:22][N:21]([CH3:23])[C:18]1[CH:19]=[CH:20][C:15]([C:14]([NH:13][C:6]2[CH:7]=[CH:8][C:9]3[NH:10][C:37]([C:36]4[CH:35]=[CH:34][C:33]([C:30]5[CH:31]=[CH:32][C:27]([N:26]([CH3:25])[CH3:41])=[CH:28][CH:29]=5)=[CH:40][CH:39]=4)=[N:1][C:4]=3[CH:5]=2)=[O:24])=[CH:16][CH:17]=1
Reactant: CN(C)c1ccc(C(=O)Nc2ccc([N+](=O)[O-])c([N+](=O)[O-])c2)cc1
Reactant: CN(C)c1ccc(-c2ccc(C=O)cc2)cc1
Product: CN(C)c1ccc(C(=O)Nc2ccc3[nH]c(-c4ccc(-c5ccc(N(C)C)cc5)cc4)nc3c2)cc1

Procedure:
Compound 220 was prepared according to the procedure similar to that described in Scheme III from N-(3,4-dinitrophenyl)-4-dimethylaminobenzamide and 4-(4-dimethylaminophenyl)benzaldehyde. [M+H]+ calcd for C30H29N5O: 476.24; found: 475.98.
Reaction SMILES: [NH2:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][C@@H:8]([NH:12][C:13](=[O:16])[CH2:14][CH3:15])[CH2:9]2)=[CH:4][CH:3]=1.[CH:17]([C:20]1[CH:25]=[CH:24][C:23]([S:26](Cl)(=[O:28])=[O:27])=[CH:22][CH:21]=1)([CH3:19])[CH3:18]>N1C=CC=CC=1.ClCCl>[CH:17]([C:20]1[CH:25]=[CH:24][C:23]([S:26]([NH:1][C:2]2[CH:11]=[C:10]3[C:5]([CH2:6][CH2:7][C@@H:8]([NH:12][C:13](=[O:16])[CH2:14][CH3:15])[CH2:9]3)=[CH:4][CH:3]=2)(=[O:28])=[O:27])=[CH:22][CH:21]=1)([CH3:19])[CH3:18]
Reactant: CC(C)c1ccc(S(=O)(=O)Cl)cc1
Reactant: CCC(=O)N[C@@H]1CCc2ccc(N)cc2C1
Solvent: c1ccncc1
Solvent: ClCCl
Product: CCC(=O)N[C@@H]1CCc2ccc(NS(=O)(=O)c3ccc(C(C)C)cc3)cc2C1
Temperature: 5 °C
Reaction time: 3 h
Yield: 89.6 %

Procedure:
(R)—N-(7-Amino-1,2,3,4-tetrahydro-naphthalen-2-yl)-propionamide (0.34 g, 1.56 mmol) was dissolved in pyridine-dichloromethane (1:2, 30 mL) and cooled to 5° C. 4-Isopropylbenzenesulfonyl chloride (0.37 g, 1.69 mmol) was added and the solution stirred at 5° C. for 3 h. Solution was evaporated, partitioned between ethyl acetate and water, and the organic phase separated and dried over MgSO4. The filtered solution was concentrated to give the product as a yellow oil (0.56 g, 90%).
Reaction SMILES: [N:1]1[C:10]2[C:5](=[N:6][CH:7]=[CH:8][CH:9]=2)[C:4]([NH2:11])=[CH:3][CH:2]=1.[H-].[Na+].[C:14]1([S:20](Cl)(=[O:22])=[O:21])[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1>C1COCC1>[N:1]1[C:10]2[C:5](=[N:6][CH:7]=[CH:8][CH:9]=2)[C:4]([NH:11][S:20]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)(=[O:22])=[O:21])=[CH:3][CH:2]=1
Reactant: O=S(=O)(Cl)c1ccccc1
Reactant: Nc1ccnc2cccnc12
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: O=S(=O)(Nc1ccnc2cccnc12)c1ccccc1
Temperature: 25 °C
Reaction time: 12 h
Yield: 25.6 %

Procedure:
[1,5]Naphthyridin-4-ylamine (Intermediate 486) (60 mg, 0.41 mmol) was added to a suspension of NaH (60% in mineral oil; 25 mg, 0.53 mmol) in THF (2 ml) at 0° C. followed by a solution of benzenesulfonyl chloride (95 mg, 0.53 mmol) in THF (1 ml). The mixture was stirred at room temperature for 12 h. After completion, the reaction was quenched with water (5 ml) and the aqueous phase was extracted with EtOAc (30 ml). The organic phase was washed with brine, dried (Na2SO4) and concentrated in vacuo. The crude residue was purified by column chromatography with DCM/MeOH (98:2) as the eluent to give the title compound (30 mg, 30%).
Reaction SMILES: Cl.[NH2:2][CH2:3][CH2:4][CH2:5][CH2:6][NH:7][S:8]([CH3:11])(=[O:10])=[O:9].Cl[C:13]1[C:22]2[C:17](=[CH:18][C:19]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)=[CH:20][CH:21]=2)[N:16]=[CH:15][C:14]=1[N+:29]([O-:31])=[O:30].C(N(CC)CC)C.O>CN1C(=O)CCC1>[N+:29]([C:14]1[CH:15]=[N:16][C:17]2[C:22]([C:13]=1[NH:2][CH2:3][CH2:4][CH2:5][CH2:6][NH:7][S:8]([CH3:11])(=[O:10])=[O:9])=[CH:21][CH:20]=[C:19]([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[CH:18]=2)([O-:31])=[O:30]
Reactant: CS(=O)(=O)NCCCCN
Reactant: O=[N+]([O-])c1cnc2cc(-c3ccccc3)ccc2c1Cl
Agent: Cl
Solvent: CN1CCCC1=O
Solvent: O
Solvent: CCN(CC)CC
Product: CS(=O)(=O)NCCCCNc1c([N+](=O)[O-])cnc2cc(-c3ccccc3)ccc12
Temperature: 25 °C
Reaction time: 8 h
Yield: 82.7 %

Procedure:
N-(4-aminobutyl)methanesulfonamide hydrochloride (7.8 g, 39 mmol) was added to a suspension of 4-chloro-3-nitro-7-phenylquinoline (35 mmol) and triethylamine (8.0 g, 79 mmol) in NMP (80 mL), and the reaction was stirred at ambient temperature overnight. The resulting solution was poured into water (350 mL) to form a solid, which was isolated by filtration, washed with water, air-dried, and recrystallized from acetonitrile to provide 12.0 g of N-[4-(3-nitro-7-phenylquinolin-4-ylamino)butyl]methanesulfonamide as yellow plates.
Reaction SMILES: [NH:1]1[CH:5]=[CH:4][C:3]([C:6]2[C:14]3[C:9](=[CH:10][N:11]=[C:12]([C:15]4[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=4)[CH:13]=3)[N:8](C3CCCCO3)[N:7]=2)=[N:2]1>Cl.O1CCOCC1>[NH:1]1[CH:5]=[CH:4][C:3]([C:6]2[C:14]3[C:9](=[CH:10][N:11]=[C:12]([C:15]4[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=4)[CH:13]=3)[NH:8][N:7]=2)=[N:2]1
Reactant: c1cncc(-c2cc3c(-c4cc[nH]n4)nn(C4CCCCO4)c3cn2)c1
Agent: Cl
Solvent: C1COCCO1
Product: c1cncc(-c2cc3c(-c4cc[nH]n4)n[nH]c3cn2)c1
Yield: 45.9 %

Procedure:
A mixture of 3-(1H-pyrazol-3-yl)-5-(pyridin-3-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-c]pyridine (29.36 mg, 0.08476 mmol) in 4.0 M of Hydrogen chloride in 1,4-Dioxane (5 mL) and 1,4-Dioxane (5 mL) was stirred at room temperature overnight. The reaction mixture was concentrated and the residue was purified by reverse phase HPLC to afford 193 as an off-white solid (10.2 mg, 45.9%). 1H NMR (400 MHz, DMSO) δ 13.71 (s, 1H), 13.14 (s, 1H), 9.23 (d, J=31.1 Hz, 2H), 8.72-8.55 (m, 2H), 8.43 (s, 1H), 7.91 (s, 1H), 7.53 (dd, J=8.0, 4.8 Hz, 1H), 6.84 (s, 1H); ESI MS m/z=263.0 (M+1)
Reaction SMILES: [NH2:1][C:2]1[C:7]([NH2:8])=[CH:6][CH:5]=[CH:4][C:3]=1[N+:9]([O-:11])=[O:10].[C:12](O)(=[O:16])[C:13](O)=[O:14]>C(O)(=O)C>[OH:14][C:13]1[C:12]([OH:16])=[N:1][C:2]2[C:7](=[CH:6][CH:5]=[CH:4][C:3]=2[N+:9]([O-:11])=[O:10])[N:8]=1
Reactant: Nc1cccc([N+](=O)[O-])c1N
Reactant: O=C(O)C(=O)O
Solvent: CC(=O)O
Product: O=[N+]([O-])c1cccc2nc(O)c(O)nc12
Temperature: 25 °C

Procedure:
4 g (26.12 mmol) of 2,3-diaminonitrobenzene and 6.59 g (52.24 mmol) of commercial oxalic acid were dissolved in 50% acetic acid, and reaction was allowed at boiling point under an argon stream for 3 hr. After the reaction was over, the reaction mixture was cooled to room temperature, and the crystal precipitated was filtered out.
Reaction SMILES: [CH2:1]([C@@H:8]1[C@@H:16]([OH:17])[C@H:15]([CH3:18])[O:14][C:13](=[O:19])[C@@H:12]([NH:20][C:21](=[O:27])[O:22][C:23]([CH3:26])([CH3:25])[CH3:24])[CH2:11][O:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.FC(F)(F)S(O[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=1[Si](C)(C)C)(=O)=O.[F-].[Cs+].[Na+].[Cl-]>CC#N>[CH2:1]([C@@H:8]1[C@@H:16]([O:17][C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[C@H:15]([CH3:18])[O:14][C:13](=[O:19])[C@@H:12]([NH:20][C:21](=[O:27])[O:22][C:23]([CH3:26])([CH3:25])[CH3:24])[CH2:11][O:10][CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: C[Si](C)(C)c1ccccc1OS(=O)(=O)C(F)(F)F
Reactant: C[C@@H]1OC(=O)[C@@H](NC(=O)OC(C)(C)C)COC[C@H](Cc2ccccc2)[C@H]1O
Agent: [Cl-]
Agent: [Cs+]
Agent: [F-]
Solvent: CC#N
Product: C[C@@H]1OC(=O)[C@@H](NC(=O)OC(C)(C)C)COC[C@H](Cc2ccccc2)[C@H]1Oc1ccccc1
Temperature: 25 °C
Reaction time: 48 h
Yield: 11.5 %

Procedure:
To a solution of tert-butyl ((3S,7S,8R,9S)-7-benzyl-8-hydroxy-9-methyl-2-oxo-1,5-dioxonan-3-yl)carbamate (500 mg, 1.32 mmol, 1.00 equiv) in anhydrous CH3CN (13 mL) were added 2-(trimethylsilyl)phenyl trifluoromethanesulfonate (0.480 mL, 1.98 mmol, 1.50 equiv) followed by CsF (500 mg, 3.29 mmol, 2.50 equiv). The resulting mixture was stirred at room temperature for 2 d. The reaction was then poured into ½ sat'd NaCl solution (20 mL), extracted with EtOAc (3×20 mL), and the combined organic extracts were dried over MgSO4, filtered, and concentrated to provide an oily yellow suspension. This was purified by automated silica gel column chromatograpy to provide tert-butyl ((3S,7S,8R,9S)-7-benzyl-9-methyl-2-oxo-8-phenoxy-1,5-dioxonan-3-yl)carbamate (69 mg, 11%) as an amorphous light yellow solid: 1H NMR (400 MHz, CDCl3) δ 7.34-7.20 (m, 5H), 7.20-7.04 (m, 4H), 7.02-6.88 (d, J=8.7 Hz, 4H), 5.20-5.02 (dq, J=9.1, 6.4 Hz, 2H), 4.71-4.57 (m, 1H), 4.37-4.21 (t, J=8.9 Hz, 1H), 4.00-3.88 (dd, J=11.6, 7.3 Hz, 1H), 3.60-3.44 (s, 2H), 3.38-3.21 (m, 1H), 3.07-2.93 (dd, J=13.6, 3.1 Hz, 1H), 2.37-2.21 (t, J=12.5 Hz, 1H), 2.22-2.09 (m, 1H), 1.46-1.40 (s, 9H), 1.40-1.34 (d, J=6.4 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 172.29, 159.20, 154.98, 139.50, 129.75, 129.11, 128.42, 126.19, 121.34, 115.48, 81.96, 80.19, 75.39, 72.88, 72.08, 52.98, 47.56, 35.29, 28.29, 18.98; ESIMS m/z 478.6 ([M+Na]+).
Reaction SMILES: Cl[C:2]1[N:7]=[CH:6][N:5]=[C:4]([N:8]2[CH2:13][CH2:12][N:11]([C:14]([O:16][CH2:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:15])[CH2:10][CH2:9]2)[CH:3]=1.N.[H][H]>CO.[OH-].[Pd+2].[OH-].[C]>[N:7]1[CH:2]=[CH:3][C:4]([N:8]2[CH2:9][CH2:10][N:11]([C:14]([O:16][CH2:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:15])[CH2:12][CH2:13]2)=[N:5][CH:6]=1
Reactant: CC(C)(C)COC(=O)N1CCN(c2cc(Cl)ncn2)CC1
Reactant: [H][H]
Agent: [Pd+2]
Agent: N
Agent: [OH-]
Solvent: CO
Product: CC(C)(C)COC(=O)N1CCN(c2ccncn2)CC1
Yield: 33.1 %

Procedure:
2,2-Dimethylpropyl 4-(6-chloropyrimidin-4-yl)-1-piperazinecarboxylate (68 mg) obtained in Example 4 was dissolved in methanol (3 mL), and 0.5 ml of aqueous ammonia and a catalytic amount of palladium hydroxide-carbon were added thereto, and stirred in a hydrogen atmosphere at room temperature for 2 hours, and the reaction liquid was filtered. The filtrate was evaporated, and the resulting residue was diluted with ethyl acetate, washed with water and saturated saline water, and dried with anhydrous sodium sulfate. The solvent was evaporated away and the resulting residue was isolated and purified through thin-layer silica gel chromatography (hexane/ethyl acetate=1/1) to obtain 20 mg of the entitled compound as an oil.
Reaction SMILES: [Si:1]([O:8][C@H:9]([C:55]1[CH:64]=[CH:63][C:62]([OH:65])=[C:61]2[C:56]=1[CH:57]=[CH:58][C:59](=[O:66])[NH:60]2)[CH2:10][NH:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16]CCCNC(C1C=C(S(C2C=C3C(=C(C)C=2)N=CC(C(N)=O)=C3NC2C=CC=C(OC)C=2)(=O)=O)C=CC=1)=O)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[CH3:67][O:68][C:69]1[CH:70]=[C:71]([NH:75][C:76]2[C:85]3[C:80](=[C:81]([CH3:110])[CH:82]=[C:83]([S:86]([C:89]4[CH:94]=[CH:93][CH:92]=[C:91]([C:95](=[O:109])[NH:96][C:97]5[CH:102]=[CH:101][C:100](C#CCCC=O)=[CH:99][CH:98]=5)[CH:90]=4)(=[O:88])=[O:87])[CH:84]=3)[N:79]=[CH:78][C:77]=2[C:111]([NH2:113])=[O:112])[CH:72]=[CH:73][CH:74]=1>>[Si:1]([O:8][C@H:9]([C:55]1[CH:64]=[CH:63][C:62]([OH:65])=[C:61]2[C:56]=1[CH:57]=[CH:58][C:59](=[O:66])[NH:60]2)[CH2:10][NH:11][CH2:12][CH2:13][CH2:14][C:15]#[C:16][C:100]1[CH:101]=[CH:102][C:97]([NH:96][C:95]([C:91]2[CH:90]=[C:89]([S:86]([C:83]3[CH:84]=[C:85]4[C:80](=[C:81]([CH3:110])[CH:82]=3)[N:79]=[CH:78][C:77]([C:111]([NH2:113])=[O:112])=[C:76]4[NH:75][C:71]3[CH:72]=[CH:73][CH:74]=[C:69]([O:68][CH3:67])[CH:70]=3)(=[O:88])=[O:87])[CH:94]=[CH:93][CH:92]=2)=[O:109])=[CH:98][CH:99]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]
Reactant: COc1cccc(Nc2c(C(N)=O)cnc3c(C)cc(S(=O)(=O)c4cccc(C(=O)NCCCCCCCCNC[C@H](O[Si](C)(C)C(C)(C)C)c5ccc(O)c6[nH]c(=O)ccc56)c4)cc23)c1
Reactant: COc1cccc(Nc2c(C(N)=O)cnc3c(C)cc(S(=O)(=O)c4cccc(C(=O)Nc5ccc(C#CCCC=O)cc5)c4)cc23)c1
Product: COc1cccc(Nc2c(C(N)=O)cnc3c(C)cc(S(=O)(=O)c4cccc(C(=O)Nc5ccc(C#CCCCNC[C@H](O[Si](C)(C)C(C)(C)C)c6ccc(O)c7[nH]c(=O)ccc67)cc5)c4)cc23)c1

Procedure:
The title compound was synthesized in a manner analogous to that described for Intermediate 148, using Intermediate 115 in place of Intermediate 112. ES/MS calcd. for C53H57N6O8SSi+ 965.4. Found m/z=965.4 (M+H)+.
Reaction SMILES: C([O:3][CH:4](OCC)[C:5]1[CH:10]=[CH:9][C:8]([CH:11]=[CH:12][C:13]([CH3:20])=[CH:14][C:15]([O:17][CH2:18][CH3:19])=[O:16])=[CH:7][CH:6]=1)C.[C:24]1([C:30]([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)([CH3:34])[CH:31](O)[OH:32])[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[C:24]1([C:30]2([C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)[CH2:31][O:32][CH:4]([C:5]3[CH:6]=[CH:7][C:8]([CH:11]=[CH:12][C:13]([CH3:20])=[CH:14][C:15]([O:17][CH2:18][CH3:19])=[O:16])=[CH:9][CH:10]=3)[O:3][CH2:34]2)[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1
Reactant: CCOC(=O)C=C(C)C=Cc1ccc(C(OCC)OCC)cc1
Reactant: CC(c1ccccc1)(c1ccccc1)C(O)O
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: Cc1ccccc1
Product: CCOC(=O)C=C(C)C=Cc1ccc(C2OCC(c3ccccc3)(c3ccccc3)CO2)cc1

Procedure:
The following are placed in a 250 ml reactor fitted with Dean-Stark apparatus: 70 ml of toluene, 3.5 g (0.011 M) of ethyl 5-(4-diethoxymethylphenyl)-3-methylpenta-2,4-dienoate, 5.0 g (0.011 M) of 2,2-diphenylpropanediol and finally 0.5 g of para-toluenesulphonic acid.
Reaction SMILES: COC[O:4][CH2:5][CH:6]1[CH:11]([N:12]2[C:20](=[O:21])[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[C:13]2=[O:22])[CH2:10][CH:9]2[CH2:23][CH:7]1[C:8]2([CH3:25])[CH3:24]>Cl.CO>[OH:4][CH2:5][CH:6]1[CH:11]([N:12]2[C:13](=[O:22])[C:14]3[C:19](=[CH:18][CH:17]=[CH:16][CH:15]=3)[C:20]2=[O:21])[CH2:10][CH:9]2[CH2:23][CH:7]1[C:8]2([CH3:25])[CH3:24]
Reactant: COCOCC1C(N2C(=O)c3ccccc3C2=O)CC2CC1C2(C)C
Agent: Cl
Solvent: CO
Product: CC1(C)C2CC(N3C(=O)c4ccccc4C3=O)C(CO)C1C2
Yield: 100 %

Procedure:
rac-2-{2-[(Methoxymethoxy)methyl]-6,6-dimethylbicyclo[3.1.1]hept-3-yl}-1H-isoindole-1,3(2H)-dione (0.97 g, 2.82 mmol) was stirred with hydrogen chloride-methanol (20 mL, 10% w/v) at room temperature for 1 day. After completion of the reaction, the reaction solution was evaporated under reduced pressure, and the residue was mixed with saturated aqueous sodium hydrogen carbonate and extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate and evaporated under reduced pressure to give the desired product (100% yield).
Reaction SMILES: [NH2:1][CH2:2][C:3]([NH:6][CH2:7][C:8]([O:10]CC)=O)([CH3:5])[CH3:4]>CN(C=O)C>[CH3:4][C:3]1([CH3:5])[CH2:2][NH:1][C:8](=[O:10])[CH2:7][NH:6]1
Reactant: CCOC(=O)CNC(C)(C)CN
Solvent: CN(C)C=O
Product: CC1(C)CNC(=O)CN1
Temperature: 25 °C

Procedure:
A solution of ethyl 2-(1-amino-2-methylpropan-2-ylamino)acetate (0.8 g, 4.7 mmol) in DMF (20 mL) was stirred at reflux for 1 h. After it was cooled to room temperature, the mixture was concentrated to give the crude product, which was directly used for the next step. MS (ESI): 129 (MH+).