Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH:1][C:2]([CH3:18])([CH3:17])[CH2:3][N:4]([CH3:16])[C:5]([C:7]1[C:11]([N+:12]([O-])=O)=[CH:10][N:9]([CH3:15])[N:8]=1)=[O:6]>C(O)C.[Pd]>[NH2:12][C:11]1[C:7]([C:5]([N:4]([CH2:3][C:2]([OH:1])([CH3:17])[CH3:18])[CH3:16])=[O:6])=[N:8][N:9]([CH3:15])[CH:10]=1
Reactant: CN(CC(C)(C)O)C(=O)c1nn(C)cc1[N+](=O)[O-]
Agent: [Pd]
Solvent: CCO
Product: CN(CC(C)(C)O)C(=O)c1nn(C)cc1N
Temperature: 25 °C
Reaction time: 16 h
Yield: 94 %

Procedure:
A solution of N-(2-hydroxy-2-methylpropyl)-N,1-dimethyl-4-nitro-1H-pyrazole-3-carboxamide (1.2 g, 4.7 mmol) in ethanol (30 ml) was flushed with argon and treated with palladium on carbon 10% (120 mg, 1.13 mmol). The reaction mixture was evacuated and flushed with hydrogen and stirred at ambient temperature for 16 h. The reaction mixture was filtered, washed with ethanol and concentrated in vacuo to yield the product as dark red oil (1.0 g, 80%) which was used without any further purification.
Reaction SMILES: Cl.C(N([CH2:13][CH3:14])CCCN=C=NCC)C.[OH:15]N1C2C=CC=CC=2N=N1.Cl.[NH2:26][C@H:27]([C:30]1[CH:31]=[N:32][C:33]([C:36]([F:39])([F:38])[F:37])=[CH:34][CH:35]=1)[CH2:28][OH:29].C(N(CC)C(C)C)(C)C>C1COCC1.O>[OH:29][CH2:28][C@H:27]([NH2:26])[C:30]1[CH:31]=[N:32][C:33]([C:36]([F:37])([F:38])[F:39])=[CH:34][CH:35]=1.[C:35]1([C@H:30]2[CH2:31][C@@H:27]2[C:28]([OH:15])=[O:29])[CH:14]=[CH:13][CH:36]=[CH:33][CH:34]=1
Reactant: CCN=C=NCCCN(CC)CC
Reactant: On1nnc2ccccc21
Agent: Cl
Agent: N[C@@H](CO)c1ccc(C(F)(F)F)nc1
Solvent: CCN(C(C)C)C(C)C
Solvent: O
Solvent: C1CCOC1
Product: O=C(O)[C@H]1C[C@@H]1c1ccccc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
N-(3-Diethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (0.39 g, 2.03 mmol) and 1-hydroxybenzotriazole (0.366 g, 2.71 mmol) were added to a stirred mixture of IM46 (0.22 g, 1.36 mmol) and commercially available (R)-2-amino-2-(6-trifluoromethyl-pyridin-3-yl)-ethanol hydrochloride (Supplier Netchem Inc., Catalog No 517882) (0.494 g, 2.03 mmol) and N,N-diisopropylethylamine (0.472 ml, 2.71 mmol) in THF (20 ml). The solution was stirred at rt overnight. Water was added and the mixture was extracted with EtOAc (3×80 ml). The combined organic phases were washed with brine, dried over MgSO4, filtered and the solvent was evaporated of in vac. The crude product was purified by silica gel chromatography (EtOAc in heptanes 10:1). Yield of Compound 22 475 mg (78%). 1H-NMR (500 MHz, DMSO) δ 8.77 (d, 1H), 8.74 (s, 1H), 8.00 (d, 1H), 7.88 (d, 1H), 7.27 (m, 2H), 7.18 (m, 1H), 7.13 (d, 2H), 5.04 (m, 2H), 3.64 (m, 2H), 2.22 (m, 1H), 2.07 (m, 1H), 1.37 (m, 1H), 1.37 (m, 1H), 1.23 (m, 1H). LC-MS (m/z) 351.1 (MH+), tR=1.51 min (method A).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[C:12]([OH:14])=O)[N:8]=[CH:7][N:6]=[C:5]2[NH:15][CH:16]([C:18]1[NH:22][C:21]2[CH:23]=[CH:24][C:25]([Cl:27])=[CH:26][C:20]=2[N:19]=1)[CH3:17].FC1C(OC(N(C)C)=[N+](C)C)=C(F)C(F)=C(F)C=1F.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C.C(OC([NH:70][CH2:71][CH2:72][CH2:73][NH:74][CH2:75][CH3:76])=O)(C)(C)C.FC(F)(F)C(O)=O>CS(C)=O>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[C:12]([N:74]([CH2:73][CH2:72][CH2:71][NH2:70])[CH2:75][CH3:76])=[O:14])[N:8]=[CH:7][N:6]=[C:5]2[NH:15][CH:16]([C:18]1[NH:22][C:21]2[CH:23]=[CH:24][C:25]([Cl:27])=[CH:26][C:20]=2[N:19]=1)[CH3:17]
Reactant: CC(Nc1ncnc2cc(C(=O)O)c(Cl)cc12)c1nc2cc(Cl)ccc2[nH]1
Reactant: CCNCCCNC(=O)OC(C)(C)C
Agent: CN(C)C(Oc1c(F)c(F)c(F)c(F)c1F)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: O=C(O)C(F)(F)F
Solvent: CS(C)=O
Product: CCN(CCCN)C(=O)c1cc2ncnc(NC(C)c3nc4cc(Cl)ccc4[nH]3)c2cc1Cl

Procedure:
Prepared analogously to Example 37a from 6-chloro-4-[1-(5-chloro-1H-benzimidazol-2-yl)-ethylamino]-7-hydroxycarbonyl-quinazoline, pentafluorophenyl-tetramethyluronium-hexafluorophosphate (PFTU), diisopropylethylamine and N-(3-tert.-butyloxycarbonylamino-propyl)-ethylamine in DMSO at ambient temperature and subsequent treatment with trifluoroacetic acid.
Reaction SMILES: [I:1][C:2]1[CH:12]=[N:11][C:5]2[NH:6][CH2:7][C:8](=[O:10])[NH:9][C:4]=2[CH:3]=1.Br[CH:14]([C:16]1[C:21]([Cl:22])=[C:20]([F:23])[CH:19]=[CH:18][C:17]=1[F:24])[CH3:15]>>[Cl:22][C:21]1[C:20]([F:23])=[CH:19][CH:18]=[C:17]([F:24])[C:16]=1[CH:14]([N:9]1[C:8](=[O:10])[CH2:7][NH:6][C:5]2[N:11]=[CH:12][C:2]([I:1])=[CH:3][C:4]1=2)[CH3:15]
Reactant: O=C1CNc2ncc(I)cc2N1
Reactant: CC(Br)c1c(F)ccc(F)c1Cl
Product: CC(c1c(F)ccc(F)c1Cl)N1C(=O)CNc2ncc(I)cc21
Yield: 11 %

Procedure:
7-Iodo-3,4-dihydro-1H-pyrido[2,3-b]pyrazin-2-one (2.935 g) was treated with 2-(1-bromoethyl)-3-chloro-1,4-difluorobenzene (Preparation 3) as in General Procedure 1 to give the title compound as an orange solid (11% yield). LCMS: m/z=449.86 (M+H+), 1H-NMR (DMSO-d6, 400 MHz) δ 1.79 (3H, m), 2.73 (1H, s), 2.89 (1H, s), 5.76 (1H, m), 6.96 (1H, s), 7.29 (1H, m), 7.43 (1H, m), 7.62 (1H, s), 7.83 (1H, m).
Reaction SMILES: [C:1]([C:3]([C:9]1[CH:10]=[C:11]([CH:16]=[CH:17][CH:18]=1)[C:12]([O:14]C)=[O:13])([CH3:8])[CH2:4][CH:5]1[CH2:7][CH2:6]1)#[N:2].O.[OH-].[Li+]>O1CCCC1.CO.O>[C:1]([C:3]([C:9]1[CH:10]=[C:11]([CH:16]=[CH:17][CH:18]=1)[C:12]([OH:14])=[O:13])([CH3:8])[CH2:4][CH:5]1[CH2:7][CH2:6]1)#[N:2]
Reactant: COC(=O)c1cccc(C(C)(C#N)CC2CC2)c1
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Solvent: CO
Product: CC(C#N)(CC1CC1)c1cccc(C(=O)O)c1
Temperature: 25 °C
Reaction time: 4 h
Yield: 67.6 %

Procedure:
To a solution of methyl 3-(1-cyano-2-cyclopropyl-1-methylethyl)benzoate (120 mg, 0.49 mmol) in tetrahydrofuran/methanol/water (=3.0 mL/1.0 mL/1.0 mL) was added lithium hydroxide monohydrate (40 mg, 0.99 mmol), and the reaction mixture was stirred at room temperature for 4 hr. The mixture was concentrated under reduced pressure, and the obtained aqueous solution was adjusted to pH 5 by adding 1N hydrochloric acid. The mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate/hexane=50/50→100/0) to give the title compound (76 mg, 66%) as a colorless oil.
Reaction SMILES: C(OC(=O)[NH:7][C:8]1[CH:13]=[CH:12][C:11]([F:14])=[C:10]([Cl:15])[C:9]=1[Cl:16])(C)(C)C.FC(F)(F)C(O)=O.C(=O)(O)[O-].[Na+]>ClCCl>[Cl:16][C:9]1[C:10]([Cl:15])=[C:11]([F:14])[CH:12]=[CH:13][C:8]=1[NH2:7]
Reactant: CC(C)(C)OC(=O)Nc1ccc(F)c(Cl)c1Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: Nc1ccc(F)c(Cl)c1Cl
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 75.2 %

Procedure:
To an oven-dried, N2-purged, 100-mL, round-bottomed flask containing a magnetic stir bar were added the product of Example 192B (3.08 g, 11.0 mmol) and dichloromethane (25 mL). The flask was sealed with a septum and cooled to 0° C. in an ice bath. Trifluoroacetic acid (18 mL) was added dropwise via syringe. The brown solution was stirred at 0° C. for 30 minutes and then allowed to warm to room temperature for 2 hours. The mixture was transferred to a large Erlenmeyer flask and the acid was neutralized by the careful addition of saturated aqueous sodium bicarbonate. The mixture was transferred to a separatory funnel and extracted with dichloromethane (3×25 mL). The combined organic extracts were dried over magnesium sulfate, filtered, and concentrated by rotary evaporator to give a brown semi-solid. The product was purified by flash chromatography (silica gel: 20% ethyl acetate, 80% hexanes, product Rf˜0.3) to give 1.49 g (81%) of the title compound as a pink solid. MS (ESI−) m/z 178.0 (M−H); 1H NMR (DMSO-d6) δ 5.53 (br s, 2H), 6.77 (dd, J=9.2, 5.1 Hz, 1H), 7.13 (dd, J=9.2, 9.2 Hz, 1H).
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([CH2:8][C:9]([O:11]CC)=[O:10])[CH:5]=[CH:4][C:3]=1[C:14]1[CH:19]=[CH:18][C:17]([F:20])=[CH:16][C:15]=1[F:21].[OH-].[Na+]>O>[F:1][C:2]1[CH:7]=[C:6]([CH2:8][C:9]([OH:11])=[O:10])[CH:5]=[CH:4][C:3]=1[C:14]1[CH:19]=[CH:18][C:17]([F:20])=[CH:16][C:15]=1[F:21]
Reactant: CCOC(=O)Cc1ccc(-c2ccc(F)cc2F)c(F)c1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: O=C(O)Cc1ccc(-c2ccc(F)cc2F)c(F)c1

Procedure:
The ester (650 mg.) was mixed with water (5 ml.), industrial methylated spirits (IMS) (5 ml.) and aqueous sodium hydroxide (0.4 ml; 18N), and refluxed for 1 hour. IMS was distilled and the residue acidified with dilute hydrochloric acid. The precipitate was filtered, washed with water, dried and recrystallised from 80-100 petroleum ether to give colourless needle clusters of 2,2',4'-trifluoro-4-biphenylylacetic acid having a m.p. of 145°-147° C.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([O:11][CH2:12][CH:13]2[CH2:17][C:16]3[CH:18]=[CH:19][CH:20]=[C:21](Br)[C:15]=3[O:14]2)(=[O:10])=[O:9])=[CH:4][CH:3]=1.[Cl:23][C:24]1[CH:25]=[C:26](B(O)O)[CH:27]=[CH:28][CH:29]=1.C(=O)([O-])[O-].[K+].[K+]>CC1C=CC=CC=1[P](C1C=CC=CC=1C)([Pd](Cl)(Cl)[P](C1=C(C)C=CC=C1)(C1C=CC=CC=1C)C1C=CC=CC=1C)C1C=CC=CC=1C>[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([O:11][CH2:12][CH:13]2[CH2:17][C:16]3[CH:18]=[CH:19][CH:20]=[C:21]([C:28]4[CH:27]=[CH:26][CH:25]=[C:24]([Cl:23])[CH:29]=4)[C:15]=3[O:14]2)(=[O:10])=[O:9])=[CH:4][CH:3]=1
Reactant: OB(O)c1cccc(Cl)c1
Reactant: Cc1ccc(S(=O)(=O)OCC2Cc3cccc(Br)c3O2)cc1
Agent: Cc1ccccc1[P](c1ccccc1C)(c1ccccc1C)[Pd](Cl)(Cl)[P](c1ccccc1C)(c1ccccc1C)c1ccccc1C
Agent: O=C([O-])[O-]
Agent: [K+]
Product: Cc1ccc(S(=O)(=O)OCC2Cc3cccc(-c4cccc(Cl)c4)c3O2)cc1
Yield: 74.6 %

Procedure:
Treatment of (±)-(7-bromo-2,3-dihydro-1-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.50 g, 1.305 mmol) with 3-chlorophenylboronic acid (0.306 g, 1.96 mmol), dichlorobis(tri-o-tolylphosphine)-palladium(II) (0.051 g, 0.065 mmol), and potassium carbonate (0.45 g, 3.26 mmol) generally according to the procedure described for Intermediate 37 provided 0.404 g (75%) of (±)-[7-(3-chlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl 4-methylbenzenesulfonate as a light yellow solid. mp 101-103° C.; Anal. calcd. for C22H19ClO4S: C, 63.69; H, 4.62. Found: C, 63.59; H, 4.52.
Reaction SMILES: [C:1]([N:9]1[CH2:17][C@@H:16]([OH:18])[CH2:15][C@H:10]1[C:11]([O:13]C)=[O:12])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.[CH3:26][S:27](Cl)(=[O:29])=[O:28]>ClCCl>[C:1]([N:9]1[CH2:17][C@@H:16]([O:18][S:27]([CH3:26])(=[O:29])=[O:28])[CH2:15][C@H:10]1[C:11]([OH:13])=[O:12])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: COC(=O)[C@@H]1C[C@H](O)CN1C(=O)c1ccccc1
Reactant: CS(=O)(=O)Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CS(=O)(=O)O[C@H]1C[C@@H](C(=O)O)N(C(=O)c2ccccc2)C1
Reaction time: 0.5 h
Yield: 61.1 %

Procedure:
A solution of (cis)-1-benzoyl-4-hydroxy-L-proline, methyl ester (169.2 g, 0.679 mole) and triethylamine (104.2 ml, 0.747 mole) in dichloromethane (3.3 liters) was cooled to -10° C. under nitrogen and treated dropwise with methanesulfonyl chloride (59.85 ml, 0.74 mole). The reaction was stirred an additional 30 minutes at -5° C. to -10° C. and the volatiles were removed in vacuo. The residue was treated with ethyl acetate and washed with water, 1N HCl, saturated sodium bicarbonate solution, and brine. The organic solution was dried, filtered, and concentrated in vacuo. The residue was dissolved in THF (2.1 liters) and treated with 3.36 N LiOH solution (423 ml) and stirred at room temperature for 1 hour. The THF was removed in vacuo and the aqueous solution was acidified to pH 4. The resulting solid was filtered, washed with ice water, and recrystallized from 95% ethanol-ethyl acetate to afford 130 g of the title compound.
Reaction SMILES: [N:1]12[CH2:8][CH2:7][CH:4]([CH2:5][CH2:6]1)[CH:3]([OH:9])[CH2:2]2.[H-].[Na+].[CH2:12]([C:16]1[N:17]=[N:18][C:19](Cl)=[CH:20][C:21]=1[C:22]1[CH:27]=[CH:26][C:25]([O:28][CH:29]2[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]2)=[CH:24][CH:23]=1)[CH2:13][CH2:14][CH3:15].O>C1COCC1.C(OCC)(=O)C>[CH2:12]([C:16]1[N:17]=[N:18][C:19]([O:9][CH:3]2[CH:4]3[CH2:7][CH2:8][N:1]([CH2:6][CH2:5]3)[CH2:2]2)=[CH:20][C:21]=1[C:22]1[CH:23]=[CH:24][C:25]([O:28][CH:29]2[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]2)=[CH:26][CH:27]=1)[CH2:13][CH2:14][CH3:15]
Reactant: CCCCc1nnc(Cl)cc1-c1ccc(OC2CCCCC2)cc1
Reactant: OC1CN2CCC1CC2
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: CCCCc1nnc(OC2CN3CCC2CC3)cc1-c1ccc(OC2CCCCC2)cc1
Temperature: 0 °C
Reaction time: 0.25 h

Procedure:
To a stirred solution of 1-aza-bicyclo[2.2.2]octan-3-ol (0.44 mmol, 0.055 g) in THF (1 mL) at room temperature was added sodium hydride (60% dispersion in mineral oil) (0.58 mmol, 0.023 g) and continued stirring for 15 min. The reaction mixture was cooled to 0° C. using an ice bath. To this was added a solution of 3-butyl-6-chloro-4-(4-cyclohexyloxy-phenyl)-pyridazine (Example 14, 0.29 mmol, 0.1 g) in THF (1 mL). After completion of addition, the reaction mixture was warmed to 50° C. for 1 h. LCMS showed the reaction was about 50% complete, so the temperature was raised to 68° C. and the reaction was stirred over night. The reaction was poured into a mixture of water (3 mL) and ethyl acetate (5 mL). The mixture was shaken and separated. The ethyl acetate layer was washed with brine (2 mL), dried (Na2SO4), filtered and concentrated under reduced pressure. The residue was purified on a 4 g SiO2 cartridge using 4-6% (2N NH3 in MeOH) in DCM to provide 3-[6-butyl-5-(4-cyclohexyloxy-phenyl)-pyridazin-3-yloxy]-1-azabicyclo[2.2.2]octane. The amine was treated with 2N HCl in diethyl ether (2 mL) and DCM (2 mL). The volatiles were removed under reduced pressure and the salt was triturated with diethyl ether and filtered to provide the title compound (0.05 g). LCMS: m/z 437 [M+1]. 1H NMR (400 MHz, CD3OD) δ 7.92 (1H, s), 7.51-7.49 (2H, m), 7.10-7.17 (2H, m), 5.49-5.56 (1H, m), 4.41-4.50 (1H, m), 3.99-3.93 (1H, m), 3.61 (1H, d), 3.35-3.51 (4H, m), 3.14-3.21 (2H, m), 2.64-2.71 (1H, m), 2.41-2.34 (1H, m), 1.94-2.25 (5H, m), 1.77-1.87 (2H, m), 1.25-1.65 (10H, m), 0.82 (3H, t).
Reaction SMILES: CC1(C)[O:9][C:7](=[O:8])[CH2:6][C:4](=O)O1.C(=O)[C:12]1[CH:21]=[CH:20][C:17]([O:18][CH3:19])=[C:14]([O:15][CH3:16])[CH:13]=1.C(O)=O.C(N(CC)CC)C>C(Cl)(Cl)Cl>[CH3:16][O:15][C:14]1[CH:13]=[C:12]([CH2:4][CH2:6][C:7]([OH:9])=[O:8])[CH:21]=[CH:20][C:17]=1[O:18][CH3:19]
Reactant: CC1(C)OC(=O)CC(=O)O1
Reactant: COc1ccc(C=O)cc1OC
Solvent: ClC(Cl)Cl
Solvent: O=CO
Solvent: CCN(CC)CC
Product: COc1ccc(CCC(=O)O)cc1OC
Temperature: 100 °C

Procedure:
After weighing 7.2 g (0.05 mol) of Meldrum's acid and 8.3 g (0.05 mol) of veratraldehyde to 50 ml of the mixture of formic acid and triethylamine prepared according to Example 1, the reaction mixture was heated to 100° C. during 1 hour and maintained at the same temperature for further 1 hour. Then the excess of formic acid and triethylamine was distilled off under reduced pressure of 2 kPa to give a distillate of 40 ml volume. The distillation residue was dissolved in 100 ml of chloroform and extracted with 50 ml of 1N sodium hydroxide solution. The chloroform phase was extracted with 2×100 ml of 1N sodium hydroxide solution. Thereafter Example 1 was followed to give a yield of 8.6 g (81.8%), m.p.: 96°-97° C.
Reaction SMILES: [CH3:1][C:2]1[O:3][C:4]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[CH:5][C:6](=[O:8])[CH:7]=1.[Na].[Cl:16][C:17]1[CH:24]=[CH:23][C:20]([CH:21]=O)=[CH:19][CH:18]=1>[O-]CC.[Na+].C(O)C>[Cl:16][C:17]1[CH:24]=[CH:23][C:20]([CH:21]=[CH:1][C:2]2[O:3][C:4]([C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=3)=[CH:5][C:6](=[O:8])[CH:7]=2)=[CH:19][CH:18]=1
Reactant: O=Cc1ccc(Cl)cc1
Reactant: Cc1cc(=O)cc(-c2ccccc2)o1
Agent: CC[O-]
Agent: [Na+]
Agent: [Na]
Solvent: CCO
Product: O=c1cc(C=Cc2ccc(Cl)cc2)oc(-c2ccccc2)c1
Temperature: 25 °C
Reaction time: 24 h

Procedure:
2-Methyl-6-phenyl-4H-pyran-4-one (3.7 g) was dissolved in sodium ethoxide solution prepared by dissolving sodium (0.46g) in ethanol (50 ml). A solution of 4-chlorobenzaldehyde (5.6 g) in ethanol (50 ml) was added and the mixture was stirred at room temperature for 24 hours. The solid which formed was recrystallised from ethanol to give the title product (mp 169°-171° C.).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]3[CH:12]=[CH:13][C:14](=[O:16])[N:15]=[C:10]3[CH:9]([OH:17])[N:8]=[C:7]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[Cl:24])[C:6]=2[CH:25]=1.[C:26]1(=[O:32])[O:31][C:29](=[O:30])[CH2:28][CH2:27]1>>[C:26]([OH:31])(=[O:32])[CH2:27][CH2:28][C:29]([OH:16])=[O:30].[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]3[CH:12]=[CH:13][C:14](=[O:16])[N:15]=[C:10]3[CH:9]([OH:17])[N:8]=[C:7]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[Cl:24])[C:6]=2[CH:25]=1.[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]3[CH:12]=[CH:13][C:14](=[O:16])[N:15]=[C:10]3[CH:9]([OH:17])[N:8]=[C:7]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[Cl:24])[C:6]=2[CH:25]=1
Reactant: O=C1CCC(=O)O1
Agent: O=c1ccn2c(n1)C(O)N=C(c1ccccc1Cl)c1cc(Cl)ccc1-2
Product: O=C(O)CCC(=O)O

Procedure:
In the manner given in Example 43, 9-chloro-5-hydroxy-7-(o-chlorophenyl)pyrimido[1,2-a][1,4]benzodiazepin-3(5H)-one was treated with succinic anhydride to give 9-chloro-5-hydroxy-7-(o-chlorophenyl)pyrimido[1,2-a][1,4]benzodiazepin-3(5H)-one hemisuccinate.
Reaction SMILES: [CH2:1]([C:3]1[S:7][C:6]([C:8]([NH2:10])=[O:9])=[CH:5][CH:4]=1)[CH3:2].[Cl:11][CH2:12][C:13]([CH2:15]Cl)=O>>[Cl:11][CH2:12][C:13]1[N:10]=[C:8]([C:6]2[S:7][C:3]([CH2:1][CH3:2])=[CH:4][CH:5]=2)[O:9][CH:15]=1
Reactant: CCc1ccc(C(N)=O)s1
Reactant: O=C(CCl)CCl
Product: CCc1ccc(-c2nc(CCl)co2)s1
Yield: 54 %

Procedure:
In substantially the same manner as in Reference Example 47, 5-ethyl-2-thiophenecarboxamide was allowed to react with 1,3-dichloroacetone to give 4-chloromethyl-2-(5-ethyl-2-thienyl)oxazole. The yield was 54%.
Reaction SMILES: C[O:2][C:3](=[O:30])[CH2:4][CH:5]([C:12]1[CH:21]=[C:20]2[C:15]([CH2:16][CH2:17][N:18]([NH:22][C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19]2)=[CH:14][CH:13]=1)[C:6]1[CH:11]=[CH:10][N:9]=[CH:8][CH:7]=1.[OH-].[Na+]>C(O)C>[C:26]([O:25][C:23]([NH:22][N:18]1[CH2:17][CH2:16][C:15]2[C:20](=[CH:21][C:12]([CH:5]([C:6]3[CH:7]=[CH:8][N:9]=[CH:10][CH:11]=3)[CH2:4][C:3]([OH:30])=[O:2])=[CH:13][CH:14]=2)[CH2:19]1)=[O:24])([CH3:29])([CH3:27])[CH3:28]
Reactant: COC(=O)CC(c1ccncc1)c1ccc2c(c1)CN(NC(=O)OC(C)(C)C)CC2
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: CC(C)(C)OC(=O)NN1CCc2ccc(C(CC(=O)O)c3ccncc3)cc2C1
Temperature: 80 °C
Yield: 42.5 %

Procedure:
A solution of 3-[2-(tert-butyloxycarbonylamino)-1,2,3,4-tetrahydro-isoquinolin-7-yl]-3-(pyrid-4-yl)-propionic acid methyl ester {1.46 g, Reference Example 15(b)} in ethanol (100 mL) was treated with sodium hydroxide solution (6 mL, 1N). This mixture was heated at 80° C. for 9 hours and then evaporated. The residue was partitioned between ethyl acetate and water which had been adjusted to pH 6 by addition of dilute hydrochloric acid. the aqueous phase was extracted twice with ethyl acetate and the combined organics were washed with water and then evaporated to give the title compound (0.6 g) which was used without further purification.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:12][C@H:11]([O:13]CC(=O)C(C)(C)C)[CH2:10][C@@H:9]1[C@H:21]1[O:25][C:24]([CH3:27])([CH3:26])[N:23]([C:28](=[O:30])[CH3:29])[C@H:22]1[CH2:31][C:32]1[CH:37]=[C:36]([F:38])[CH:35]=[C:34]([F:39])[CH:33]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C>CS(C)=O.C(OCC)(=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:12][C:11](=[O:13])[CH2:10][C@@H:9]1[C@H:21]1[O:25][C:24]([CH3:26])([CH3:27])[N:23]([C:28](=[O:30])[CH3:29])[C@H:22]1[CH2:31][C:32]1[CH:33]=[C:34]([F:39])[CH:35]=[C:36]([F:38])[CH:37]=1)=[O:7])([CH3:2])([CH3:3])[CH3:4]
Reactant: CC(=O)N1[C@@H](Cc2cc(F)cc(F)c2)[C@@H]([C@H]2C[C@@H](OCC(=O)C(C)(C)C)CN2C(=O)OC(C)(C)C)OC1(C)C
Solvent: CCN(CC)CC
Solvent: CS(C)=O
Solvent: CCOC(C)=O
Product: CC(=O)N1[C@@H](Cc2cc(F)cc(F)c2)[C@@H]([C@H]2CC(=O)CN2C(=O)OC(C)(C)C)OC1(C)C
Reaction time: 0.83 h
Yield: 95.4 %

Procedure:
Add sulfur trioxide pyridine complex (1.99 g, 12.46 mmol) to a solution of (2R,4R)-2-[(4S,5S)-3-acetyl-4-(3,5-difluoro-benzyl)-2,2-dimethyl-oxazolidin-5-yl]-4-(3,3-dimethyl-2-oxo-butoxy)-pyrrolidine-1-carboxylic acid tert-butyl ester (2.83 g, 6.23 mmol) and triethylamine (3.5 mL, 24.9 mmol) in dimethyl sulfoxide (14 mL) at 10° C. Stir 50 minutes, dilute with ethyl acetate and wash with water, saturated aqueous sodium chloride, dry with magnesium sulfate. Purify on silica gel with dichloromethane/ethyl acetate mixtures to give the desired compound as a foam (2.69 g, 95%).
Reaction SMILES: [CH2:1]1[CH:5]2[C@@H:6]3[CH:10]=[CH:9][C@H:8]([CH:4]2[CH:3]=[CH:2]1)[CH2:7]3>Cl[Ru](=CC1C=CC=CC=1)([P](C1CCCCC1)(C1CCCCC1)C1CCCCC1)([P](C1CCCCC1)(C1CCCCC1)C1CCCCC1)Cl>[CH2:1]1[CH:5]2[CH:6]3[CH:10]=[CH:9][CH:8]([CH:4]2[CH:3]=[CH:2]1)[CH2:7]3
Reactant: C1=CC2C(C1)[C@@H]1C=C[C@H]2C1
Agent: Cl[Ru](Cl)(=Cc1ccccc1)([P](C1CCCCC1)(C1CCCCC1)C1CCCCC1)[P](C1CCCCC1)(C1CCCCC1)C1CCCCC1
Product: C1=CC2C3C=CC(C3)C2C1
Reaction time: 120 h

Procedure:
Grubbs catalyst containing MCs (approximately 1 mg) were dispersed in neat DCPD (100 mg). The MCs were ruptured with a laser or by physical crushing. After rupturing, a gel was produced in approximately 10-30 minutes, with formation of a rubbery state, and then a solid resin over time. No gelling of DCPD was evident over two weeks with uncrushed MCs; however, the latent catalyst remained active as subsequent rupture of the MCs that had been left for five days still produced a gel in approximately 45-60 minutes. A background gelling rate of approximately 1 day was obtained with prepared particles that were not free flowing.
Reaction SMILES: Cl.[CH3:2][O:3][C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1[O:14][CH3:15])[CH:10]=[N:9][CH2:8][CH2:7]2.[CH3:16][C:17]([C:19]1[CH2:23][CH2:22][CH2:21][CH:20]=1)=[O:18]>C(O)C>[CH3:2][O:3][C:4]1[C:13]([O:14][CH3:15])=[CH:12][C:11]2[CH:10]3[N:9]([CH2:8][CH2:7][C:6]=2[CH:5]=1)[CH:20]1[CH2:21][CH2:22][CH2:23][CH:19]1[C:17](=[O:18])[CH2:16]3
Reactant: CC(=O)C1=CCCC1
Reactant: COc1cc2c(cc1OC)CCN=C2
Agent: Cl
Solvent: CCO
Product: COc1cc2c(cc1OC)C1CC(=O)C3CCCC3N1CC2

Procedure:
A mixture of 23.0 g (0.1 mole) of 6,7-dimethoxy-3,4-dihydroisoquinoline hydrochloride, 23.0 g (0.2 mole) of 1-cyclopenten-1-yl methyl ketone in 25 ml of ethanol is refluxed overnight then evaporated in vacuo. The residual oil is partitioned between water and ether after which the aqueous layer is separated and washed with ether, made basic with concentrated ammonium hydroxide solution and stirred. A sticky solid material forms which is washed with water, partially dried in vacuo, dissolved in methylene chloride, dried over sodium sulfate, filtered and evaporated. The residual material is dissolved in benzene and chromatographed on alumina eluting with benzene then with benzene-15% ethyl acetate. The solid obtained is recrystallized from benzene-hexane to give 1,2,3,3a,5,6,10b,11,12,12a-decahydro-8,9-dimethoxybenzo[a]cyclopenta[f]quinolizin-12-one, M.P. 105°-114° C.
Reaction SMILES: [Br:1][C:2]1[CH:13]=[C:12]([Br:14])[C:11]([N:15]2[C:20](=[O:21])[C:19]3[CH2:22][CH2:23][CH2:24][C:18]=3[NH:17][C:16]2=[O:25])=[CH:10][C:3]=1[C:4]([O:6][CH:7]([CH3:9])[CH3:8])=[O:5].S(OC)(O[CH3:30])(=O)=O.[Na]>C(O)(C)C>[Br:1][C:2]1[CH:13]=[C:12]([Br:14])[C:11]([N:15]2[C:20](=[O:21])[C:19]3[CH2:22][CH2:23][CH2:24][C:18]=3[N:17]([CH3:30])[C:16]2=[O:25])=[CH:10][C:3]=1[C:4]([O:6][CH:7]([CH3:9])[CH3:8])=[O:5]
Reactant: CC(C)OC(=O)c1cc(-n2c(=O)[nH]c3c(c2=O)CCC3)c(Br)cc1Br
Reactant: COS(=O)(=O)OC
Agent: [Na]
Solvent: CC(C)O
Product: CC(C)OC(=O)c1cc(-n2c(=O)c3c(n(C)c2=O)CCC3)c(Br)cc1Br

Procedure:
using isopropyl 2,4-dibromo-5-(1,2,4,5,6,7-hexahydro-2,4-dioxo-3H-cyclopenta[d]pyrimidin-3-yl)-benzoate and dimethyl sulphate with sodium isopropylate in isopropanol there is obtained isopropyl 2,4-dibromo-5-(1,2,4,5,6,7-hexahydro-1-methyl-2,4-dioxo-3H-cyclopenta[d]pyrimidin-3-yl)-benzoate, 1H-NMR (CDCl3, 400 MHz) 8.03 ppm (s, 1H), 4.72 ppm (s, 1H), 5.23 ppm (m, 1H), 2.96 ppm (m, 2H), 2.83 ppm (m, 2H), 2.17 ppm (m, 2H), 1.35 ppm (d, 6H),