Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10]2[N:11]=[C:12]([NH:15]C(=O)C)[NH:13][CH:14]=2)=[CH:6][CH:5]=1)([O-:3])=[O:2].Cl.[OH-].[Na+]>CCO>[N+:1]([C:4]1[CH:5]=[CH:6][C:7]([C:10]2[N:11]=[C:12]([NH2:15])[NH:13][CH:14]=2)=[CH:8][CH:9]=1)([O-:3])=[O:2]
Reactant: CC(=O)Nc1nc(-c2ccc([N+](=O)[O-])cc2)c[nH]1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: Nc1nc(-c2ccc([N+](=O)[O-])cc2)c[nH]1
Reaction time: 3 h

Procedure:
2.7 g (11 mmol) N-[4-(4-nitrophenyl)-1H-imidazole-2-yl]acetamide was taken up in 30 mL EtOH, combined with 50 mL 50% hydrochloric acid, and stirred for 3 hr under reflux. The batch was made alkaline with 6 M NaOH and extracted with ethyl acetate. The organic phase was dried (MgSO4) [and] concentrated. The residue (0.9 g) was further used without purification.
Reaction SMILES: C1C=CC=CC=1.C(Cl)(Cl)Cl.[CH3:11][NH:12][C:13](=[O:23])[O:14][C:15]1[CH:20]=[CH:19][C:18]([NH2:21])=[C:17]([CH3:22])[CH:16]=1.[Cl:24][CH:25]([CH3:29])[C:26](Cl)=[O:27]>C(N(CC)CC)C>[CH3:11][NH:12][C:13](=[O:23])[O:14][C:15]1[CH:20]=[CH:19][C:18]([NH:21][C:26](=[O:27])[CH:25]([Cl:24])[CH3:29])=[C:17]([CH3:22])[CH:16]=1
Reactant: CC(Cl)C(=O)Cl
Reactant: CNC(=O)Oc1ccc(N)c(C)c1
Solvent: ClC(Cl)Cl
Solvent: CCN(CC)CC
Solvent: c1ccccc1
Product: CNC(=O)Oc1ccc(NC(=O)C(C)Cl)c(C)c1
Yield: 95.7 %

Procedure:
Utilizing benzene and chloroform as the solvent and triethylamine as the acid acceptor, 3-methyl-4-aminophenyl N-methylcarbamate (2.5g., 0.0139 mole) was reacted with α-chloropropionyl chloride (1.79g., 0.0141 mole) to yield the desired product as a white powder (3.6g.). Recrystallization from ethanol/water to give material with m.p. 167°-70° C.
Reaction SMILES: [CH3:1][C:2]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)=[CH2:3].[CH:10]([OH:13])([CH3:12])[CH3:11]>>[CH3:11][C:10]([OH:13])([CH2:3][CH:2]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)[CH3:1])[CH3:12]
Reactant: C=C(C)c1ccccc1
Reactant: CC(C)O
Product: CC(CC(C)(C)O)c1ccccc1

Procedure:
By reaction of α-methylstyrene with isopropanol under the conditions described in example 1, after multistage distillation, a mixture which 2-methyl-4-phenyl-2-pentanol (90.3 GC area %) was obtained. In a 300 mL autoclave, 27.7 g of this mixture were dissolved in 132.3 g of tetrahydrofuran, and 1.6 g of a catalyst according to preparation example 1 were initially charged in a catalyst basket. The autoclave was purged three times with nitrogen. This was followed by hydrogenation at 160° C. and hydrogen pressure 160 bar for 10 hours. The output was analyzed by means of gas chromatography (30 m column material DB1 ID: 0.25 mm, FD: 0.25 μm, 50° C.-5 min isothermal, −6° C./min 290° C.-219 min isothermal). The composition of the output after 10 h is reported in the table below.
Reaction SMILES: C([Li])CCC.[N:6]1[CH:11]=[CH:10][C:9]([CH:12]=[O:13])=[CH:8][CH:7]=1.[C:14]1([O:22][CH3:23])[C:15](=[CH:18][CH:19]=[CH:20][CH:21]=1)[O:16][CH3:17]>O1CCCC1.C1(C)C=CC=CC=1>[OH:13][CH:12]([C:9]1[CH:10]=[CH:11][N:6]=[CH:7][CH:8]=1)[C:21]1[CH:20]=[CH:19][CH:18]=[C:15]([O:16][CH3:17])[C:14]=1[O:22][CH3:23]
Reactant: COc1ccccc1OC
Reactant: O=Cc1ccncc1
Agent: [Li]CCCC
Solvent: Cc1ccccc1
Solvent: C1CCOC1
Product: COc1cccc(C(O)c2ccncc2)c1OC
Temperature: 25 °C
Reaction time: 2.5 h

Procedure:
In a 2 L flask, 72 g of veratrole was dissolved in 300 g of tetrahydrofuran and 155.3 g of butyllithium in toluene was added at temperatures from −10° C. to over 30° C. The mixture was stirred from 1-4 hours at ambient temperature. Then 40 g of 4-pyridinecarboxaldehyde (9) in 180 mL of toluene was added around ambient temperature. The reaction mixture was stirred from 30 minutes to 5 hours. The solution was then cooled to around 5° C. and quenched with 200 mL of water. The phases were separated and the organic phase was distilled to remove the tetrahydrofuran. The residue was taken up in toluene at −5° C. The 4-[1-hydroxy-1-(2,3-dimethoxyphenyl)methyl]pyridine (10) was collected by filtration and washed with 60 g of toluene.
Reaction SMILES: [OH:1][C:2]1[CH:9]=[CH:8][CH:7]=[CH:6][C:3]=1[CH2:4][OH:5].Cl[CH2:11][C:12]([OH:14])=[O:13].[OH-].[Na+].Cl>O>[C:12]([CH2:11][O:1][C:2]1[CH:9]=[CH:8][CH:7]=[CH:6][C:3]=1[CH2:4][OH:5])([OH:14])=[O:13]
Reactant: O=C(O)CCl
Reactant: OCc1ccccc1O
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: O=C(O)COc1ccccc1CO
Temperature: 25 °C

Procedure:
A mixture of 2-hydroxybenzyl alcohol (0.5 mol), α-chloroacetic acid (0.5 mol) and solid sodium hydroxide (1.0 mol) in water (1L) is heated at reflux for 6 h. After this time the solution is cooled to ambient temperature and acidified to pH 4 with a 10% solution of hydrogen chloride in water. The product crystalizes from the acidified solution and is isolated and dried by filtration to give 2-Carboxymethoxybenzylalcohol which is used directly in the next step.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[CH2:6][C:7]3[C:15](=[O:16])[N:14]([C:17]4[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][CH:18]=4)[N:13]=[C:12]([OH:24])[C:8]=3[NH:9][C:10]=2[CH:11]=1.[C:25](Cl)(=[O:27])[CH3:26].N1C(C)=CC=CC=1C>C1(C)C=CC=CC=1.CCOCC>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[CH2:6][C:7]3[C:15](=[O:16])[N:14]([C:17]4[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][CH:18]=4)[N:13]=[C:12]([O:24][C:25](=[O:27])[CH3:26])[C:8]=3[NH:9][C:10]=2[CH:11]=1
Reactant: CC(=O)Cl
Reactant: Cc1ccc(-n2nc(O)c3c(c2=O)Cc2ccc(Cl)cc2N3)cc1
Solvent: CCOCC
Solvent: Cc1ccccc1
Solvent: Cc1cccc(C)n1
Product: CC(=O)Oc1nn(-c2ccc(C)cc2)c(=O)c2c1Nc1cc(Cl)ccc1C2
Temperature: 25 °C
Yield: 62 %

Procedure:
A suspension of the 7-chloro-4-hydroxy-2-(4′-methylphenyl)-5,10-dihydro-2H-pyridazino[4,5-b]quinoline-1-one (755 mg), acetyl chloride (0.205 mL) and 2,6-lutidine (0.337 mL) was refluxed in toluene (6 mL) for 2 hours. The resulting mixture was cooled to room temperature. The resulting paste was diluted with ether (15 mL) and filtered in vacuo. The solids were washed with ether and ethyl acetate. The crude solids were triturated in warm ethyl acetate, then cooled to room temperature and filtered in vacuo. After drying this afforded the title compound as a light yellow solid (528 mg, 62%). mp 238-240° C.; MS 382 (m+H); NMR 2.34(s,3H), 2.41(s,3H), 3.85(s, 2H), 6.98(dd,1H,J1=8.1,J2=1.9), 7.09(d,1H,J=1.9), 7.18(d,1H,J=8.1), 7.28(d,2H,J=8.3), 7.39(d,2H,J=8.3), 9.06(s,1H); Analysis C20H16ClN3O3. 0.03M H2O expected/theoretical C 62.09/62.04H 4.24/2.27 N 10.62/10.85.
Reaction SMILES: CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C1=CC=CC=2)=O.[CH3:23][O:24][C:25]1[CH:30]=[CH:29][N:28]=[C:27]2[N:31]([CH:34]([C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=3)[CH2:35][CH2:36][OH:37])[CH:32]=[CH:33][C:26]=12.C([O-])(O)=O.[Na+]>C(Cl)Cl>[CH3:23][O:24][C:25]1[CH:30]=[CH:29][N:28]=[C:27]2[N:31]([CH:34]([C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=3)[CH2:35][CH:36]=[O:37])[CH:32]=[CH:33][C:26]=12
Reactant: COc1ccnc2c1ccn2C(CCO)c1ccccc1
Agent: CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Product: COc1ccnc2c1ccn2C(CC=O)c1ccccc1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a RT mixture of Dess-Martin periodane (1.69 g, 3.99 mmol) in DCM (50 mL) was added 3-(4-methoxy-pyrrolo[2,3-b]pyridin-1-yl)-3-phenyl-propan-1-ol (563 mg, 2.0 mmol). The reaction was stirred at RT for 2 h and then poured in a saturated solution of NaHCO3. The organic layer was separated, and the aqueous was extracted with a mixture DCM/EtOAc (2/1). The combined organic layers were dried over MgSO4, filtered and concentrated to give 3-(4-Methoxy-pyrrolo[2,3-b]pyridin-1-yl)-3-phenyl-propionaldeyde, which was used in the next step without further purification.
Reaction SMILES: [OH:1][CH2:2][C:3]1[CH:4]=[C:5]([CH:10]=[C:11]([CH3:13])[N:12]=1)[C:6]([O:8][CH3:9])=[O:7].[OH2:14]>C(Cl)(Cl)(Cl)Cl.CC#N>[CH3:9][O:8][C:6]([C:5]1[CH:10]=[C:11]([CH3:13])[N:12]=[C:3]([C:2]([OH:14])=[O:1])[CH:4]=1)=[O:7]
Reactant: O
Reactant: COC(=O)c1cc(C)nc(CO)c1
Solvent: ClC(Cl)(Cl)Cl
Solvent: CC#N
Product: COC(=O)c1cc(C)nc(C(=O)O)c1
Reaction time: 2 h

Procedure:
To a stirring mixture of 51.6 mg (0.283 mmol) of methyl 2-(hydroxymethyl)-6-methylisonicotinate in 1.6 mL of CCl4, 1.6 mL of CH3CN, and 2.4 mL of H2O was added 348 mg (1.63 mmol) of NaIO4, and 8.8 mg (0.0424 mmol) of RuCl3.(H2O)n. After 2 h, 6 mg of RuCl3.(H2O)n was added, and after 2.5 h the mixture was filtered through Celite twice with EtOAc and MeOH. The solution was concentrated and then reconcentrated with MeOH (2×) to remove H2O. Crude 4-(methoxycarbonyl)-6-methylpicolinic acid was used in the next reaction without further purification.
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].[C:7]([C:10]1[CH:16]=[CH:15][C:13]([NH2:14])=[CH:12][CH:11]=1)(=[O:9])[NH2:8].[CH3:17][C:18]1[CH:28]=[CH:27][CH:26]=[CH:25][C:19]=1[CH:20]=[CH:21][C:22](Cl)=[O:23]>CC(C)=O.O>[CH3:17][C:18]1[CH:28]=[CH:27][CH:26]=[CH:25][C:19]=1[CH:20]=[CH:21][C:22]([NH:14][C:13]1[CH:15]=[CH:16][C:10]([C:7](=[O:9])[NH2:8])=[CH:11][CH:12]=1)=[O:23]
Reactant: NC(=O)c1ccc(N)cc1
Reactant: Cc1ccccc1C=CC(=O)Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Solvent: O
Product: Cc1ccccc1C=CC(=O)Nc1ccc(C(N)=O)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 77.7 %

Procedure:
4.1 g of potassium carbonate was added to a solution of 2.0 g of 4-carbamoylaniline in 40 ml of acetone and 40 ml of water. To the mixture was gradually added 3.2 g of 2-methylcinnamoyl chloride with ice-cooling. The resulting mixture was stirred at room temperature overnight. The reaction mixture was mixed with water. The resulting precipitate was collected by filtration, washed with water and dried to obtain 3.2 g of N-(2-methylcinnamoyl)-4-carbamoylaniline as a white powder.
Reaction SMILES: [C:1]([C:4]1[C:5](=[O:15])[O:6][C:7]([OH:14])=[C:8]([C:11](=[O:13])[CH3:12])[C:9]=1[OH:10])(=[O:3])[CH3:2].COC1C=C(C=CC=1OC)C=O.[CH3:28][O:29][C:30]1[C:37]([O:38][CH3:39])=[CH:36][CH:35]=[CH:34][C:31]=1[CH:32]=O>>[C:11]([C:8]1[C:7](=[O:14])[O:6][C:5](=[O:15])[CH:4]([C:1](=[O:3])[CH:2]=[CH:32][C:31]2[CH:34]=[CH:35][CH:36]=[C:37]([O:38][CH3:39])[C:30]=2[O:29][CH3:28])[C:9]=1[OH:10])(=[O:13])[CH3:12]
Reactant: CC(=O)c1c(O)oc(=O)c(C(C)=O)c1O
Reactant: COc1cccc(C=O)c1OC
Agent: COc1ccc(C=O)cc1OC
Product: COc1cccc(C=CC(=O)C2C(=O)OC(=O)C(C(C)=O)=C2O)c1OC

Procedure:
Similarly, equimolar amounts of 3,5-diacetyl-4,6-dihydroxy-2H-pyran-2-one and 3,4-dimethoxybenzaldehyde or 2,3-dimethoxybenzaldehyde are reacted as above to yield the products, 5-acetyl-3-(3,4-dimethoxycinnamoyl)-4-hydroxy-2H-pyran-2,6(3H)-digne, m.p. 223°-225° C., and 5-acetyl-3-(2,3-dimethoxycinnamoyl)-4-hydroxy-2H-pyran-2,6(3H)-dione, m.p. 175°-176° C., respectively.
Reaction SMILES: [CH3:1][C:2]([C:4]1[CH:9]=[C:8]([O:10][CH3:11])[C:7]([OH:12])=[C:6]([O:13][CH3:14])[CH:5]=1)=[O:3].C([O-])([O-])=O.[K+].[K+].C(N(CC)CC)C.[C:28](Cl)(=[O:30])[CH3:29]>ClCCl.O>[C:28]([O:12][C:7]1[C:6]([O:13][CH3:14])=[CH:5][C:4]([C:2](=[O:3])[CH3:1])=[CH:9][C:8]=1[O:10][CH3:11])(=[O:30])[CH3:29]
Reactant: CC(=O)Cl
Reactant: COc1cc(C(C)=O)cc(OC)c1O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: ClCCl
Solvent: CCN(CC)CC
Solvent: O
Product: COc1cc(C(C)=O)cc(OC)c1OC(C)=O
Temperature: 0 °C
Reaction time: 24 h
Yield: 99 %

Procedure:
3.0 g (15.3 mmol) of 3,5-dimethoxy-4-hydroxyacetophenone is dissolved in dichloromethane (30 ml) and 2.53 g (18.3 mmol) of K2CO3 is added. Triethylamine (2.6 ml) is then added dropwise. The reaction medium is cooled down to 0° C. and acetyl chloride (1.31 ml; 18.3 mmol) is added. The mixture is stirred for 24 hours at ambient temperature then poured into ice-cooled water. After extraction with dichloromethane, the organic phase is washed with sodium chloride in a saturated aqueous solution before being dried over magnesium sulphate, filtered and concentrated under vacuum. The product obtained is purified by crystallization from ether in order to produce a white solid with a yield of 99%. Melting point: 145° C.
Reaction SMILES: [OH:1][CH2:2][CH2:3][O:4][C@H:5]1[CH2:10][CH2:9][C@H:8]([N:11]2[C:16](=[O:17])[C:15]([CH2:18][C:19]3[CH:24]=[CH:23][C:22]([C:25]4[C:26]([C:31]#[N:32])=[CH:27][CH:28]=[CH:29][CH:30]=4)=[CH:21][CH:20]=3)=[C:14]([CH2:33][CH2:34][CH3:35])[N:13]3[N:36]=[CH:37][N:38]=[C:12]23)[CH2:7][CH2:6]1.C(N(CC)CC)C.[CH3:46][S:47](Cl)(=[O:49])=[O:48]>CN(C)C1C=CN=CC=1.C(#N)C>[CH3:46][S:47]([O:1][CH2:2][CH2:3][O:4][C@H:5]1[CH2:10][CH2:9][C@H:8]([N:11]2[C:16](=[O:17])[C:15]([CH2:18][C:19]3[CH:24]=[CH:23][C:22]([C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=4[C:31]#[N:32])=[CH:21][CH:20]=3)=[C:14]([CH2:33][CH2:34][CH3:35])[N:13]3[N:36]=[CH:37][N:38]=[C:12]23)[CH2:7][CH2:6]1)(=[O:49])=[O:48]
Reactant: CS(=O)(=O)Cl
Reactant: CCCc1c(Cc2ccc(-c3ccccc3C#N)cc2)c(=O)n([C@H]2CC[C@H](OCCO)CC2)c2ncnn12
Agent: CN(C)c1ccncc1
Solvent: CC#N
Solvent: CCN(CC)CC
Product: CCCc1c(Cc2ccc(-c3ccccc3C#N)cc2)c(=O)n([C@H]2CC[C@H](OCCOS(C)(=O)=O)CC2)c2ncnn12
Temperature: 25 °C
Reaction time: 3 h

Procedure:
A mixture of 4′-({4-[trans-4-(2-hydroxyethoxy)cyclohexyl]-5-oxo-7-propyl-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl}methyl)biphenyl-2-carbonitrile (1.2 g), triethylamine (0.38 mL), methanesulfonyl chloride (0.21 mL), N,N-dimethylpyridin-4-amine (0.028 g) and acetonitrile (20 mL) was stirred at room temperature for 3 hr. The reaction mixture was washed with water and then with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography to give the title compound as a colorless solid (1.2 g, 89%).
Reaction SMILES: [CH3:1][S:2](Cl)(=[O:4])=[O:3].[NH2:6][C:7]1[CH:8]=[C:9]([C:14]2[C:19]([Cl:20])=[CH:18][C:17]([C:21]([F:24])([F:23])[F:22])=[CH:16][N:15]=2)[CH:10]=[CH:11][C:12]=1[Cl:13].C(N(CC)CC)C>C(Cl)Cl>[Cl:20][C:19]1[C:14]([C:9]2[CH:10]=[CH:11][C:12]([Cl:13])=[C:7]([N:6]([S:2]([CH3:1])(=[O:4])=[O:3])[S:2]([CH3:1])(=[O:4])=[O:3])[CH:8]=2)=[N:15][CH:16]=[C:17]([C:21]([F:24])([F:23])[F:22])[CH:18]=1
Reactant: Nc1cc(-c2ncc(C(F)(F)F)cc2Cl)ccc1Cl
Reactant: CS(=O)(=O)Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CS(=O)(=O)N(c1cc(-c2ncc(C(F)(F)F)cc2Cl)ccc1Cl)S(C)(=O)=O
Reaction time: 15 h

Procedure:
2.4 g (21.0 mmol) of methanesulfonyl chloride were slowly added dropwise to a mixture of 3.0 g (9.77 mmol) of 2-(3-amino-4-chlorophenyl)-3-chloro-5-trifluoromethylpyridine, 2.2 g (22.4 mmol) of triethylamine and 50 ml of anhydrous methylene chloride at 0°-5° C. The mixture was stirred at 20°-25° C. for about 15 hours and then washed twice with water, dried over sodium sulfate and finally concentrated. The residue was stirred with ether, filtered off with suction and dried under reduced pressure. Yield: 3.6 g (87%) of colorless crystals of melting point 230°-231° C.
Reaction SMILES: I[C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8]C)=[O:7])=[CH:4][CH:3]=1.C(N(CC)CC)C.[C:19]([C:21]1[CH:22]=[C:23]2[C:28](=[CH:29][CH:30]=1)[O:27][CH2:26][CH2:25][C:24]2([CH2:32][O:33][CH3:34])[CH3:31])#[CH:20]>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.[Cu]I.CN(C=O)C>[CH3:34][O:33][CH2:32][C:24]1([CH3:31])[C:23]2[C:28](=[CH:29][CH:30]=[C:21]([C:19]#[C:20][C:2]3[CH:11]=[CH:10][C:5]([C:6]([OH:8])=[O:7])=[CH:4][CH:3]=3)[CH:22]=2)[O:27][CH2:26][CH2:25]1
Reactant: COC(=O)c1ccc(I)cc1
Reactant: C#Cc1ccc2c(c1)C(C)(COC)CCO2
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Cu]I
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: COCC1(C)CCOc2ccc(C#Cc3ccc(C(=O)O)cc3)cc21
Reaction time: 0.25 h

Procedure:
In 11 ml of abs. DMF was successively dissolved 1.061 g (1.25 eq.) of methyl 4-iodo-benzoate, 114 mg (0.05 eq.) of bis (triphenylphosphine)palladium(II) chloride, 74.1 mg (0.12 eq.) of CuI, and 1.13 ml (2.5 eq.) of triethylamine. 701 mg (3.24 mmol) of the above prepared 6-ethynyl-4-methoxymethyl-4-methyl-chroman, dissolved in 2.7 ml of abs. DMF, was added within 1 h via dropping funnel. After 0.25 h, the reaction was quenched by pouring the reaction mixture onto crushed ice/ HCl. Extraction with diethylether, washing the organic phase twice with water, drying it over magnesium sulfate, filtration and evaporation of the solvent yielded after flash chromatography (SiO2, hexane/ ethylacetate 92/8) 630 mg of the title compound as yellowish oil.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:11][CH:10]([C:12]([OH:14])=O)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.[CH3:16][NH:17][CH3:18].Cl.CN(C)CCCN=C=NCC.O.ON1C2C=CC=CC=2N=N1>C(OCC)(=O)C.CN(C)C=O.C(N(CC)CC)C>[CH3:16][N:17]([CH3:18])[C:12]([CH:10]1[CH2:11][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH2:9]1)=[O:14]
Reactant: CC(C)(C)OC(=O)N1CC(C(=O)O)C1
Reactant: CNC
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: CN(C)C(=O)C1CN(C(=O)OC(C)(C)C)C1
Temperature: 25 °C
Reaction time: 72 h
Yield: 39.9 %

Procedure:
Under a nitrogen atmosphere, triethylamine (1.2 ml) was added to a mixture of 1-(t-butyloxycarbonyl)-azetidine-3-carboxylic acid (0.804 g), dimethylamine hydrochloride (0.489 g), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.997 g), 1-hydroxybenzotriazole hydrate (0.796 g), and dimethylformamide (8 ml), and the mixture was stirred at room temperature for 3 days. To the reaction mixture was added ethyl acetate (30 ml), and the mixture was successively washed once with water, once with hydrochloric acid, once with water, twice with saturated aqueous sodium hydrogen carbonate and twice with water. The organic layer was dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated under reduced pressure to give the title compound (0.364 g, 40%).
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.I[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[CH3:17]>>[CH3:17][C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=1[N:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1
Reactant: Cc1ccccc1I
Reactant: c1ccc2[nH]ccc2c1
Product: Cc1ccccc1-n1ccc2ccccc21

Procedure:
Prepared by Procedure C and Scheme O using 1H-indole and 1-iodo-2-methylbenzene: ESMS m/e: 208.0 (M+H)+.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8](O)[CH2:9][C:10]2[N:11](C(OC(C)(C)C)=O)[C@H:12]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[C@H:13]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[N:14]=2)=[CH:4][CH:3]=1.C(O)(C(F)(F)F)=O>ClCCl>[F:1][C:2]1[CH:3]=[CH:4][C:5](/[CH:8]=[CH:9]/[C:10]2[NH:14][C@H:13]([C:15]3[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=3)[C@H:12]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[N:11]=2)=[CH:6][CH:7]=1
Reactant: CC(C)(C)OC(=O)N1C(CC(O)c2ccc(F)cc2)=N[C@@H](c2ccccc2)[C@H]1c1ccccc1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: Fc1ccc(/C=C/C2=N[C@@H](c3ccccc3)[C@@H](c3ccccc3)N2)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 21.4 %

Procedure:
To a cold (0° C.) solution of 2-[2-(4-fluorophenyl)-2-hydroxyethyl]-cis-4,5-diphenyl-4,5-dihydro-imidazole-1-carboxylic acid, tert-butyl ester (256) (690 mg, 1.5 mmol) in dichloromethane (2 mL) is added TFA (2 mL). The reaction mixture is stirred at RT overnight. Reaction mixture is rotary evaporated and the residue purified by chromatography on silica gel; elution with dichloromethane:MeOH (9:1) gives 110 mg of the product 259. 1H NMR (CDCl3) δ 8.10 (d, 1 H), 7.60-7.35 (m, 2 H), 7.15-6.85 (m, 9 H), 6.85-6.60 (m, 4 H), 5.20 (s, 2 H); MS: m/z 343 (M++1).
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10]23[CH2:29][CH:14]4[CH2:15][C:16]([NH:18][CH2:19][C:20]([N:22]5[CH2:26][CH2:25][CH2:24][C@H:23]5[C:27]#[N:28])=[O:21])([CH2:17]2)[CH:12]([CH2:13]4)[CH2:11]3)=[CH:6][CH:5]=1)([O-])=O.O.C1COCC1.[NH4+].[Cl-]>[Fe].C(O)C>[NH2:1][C:4]1[CH:5]=[CH:6][C:7]([C:10]23[CH2:29][CH:14]4[CH2:15][C:16]([NH:18][CH2:19][C:20]([N:22]5[CH2:26][CH2:25][CH2:24][C@H:23]5[C:27]#[N:28])=[O:21])([CH2:17]2)[CH:12]([CH2:13]4)[CH2:11]3)=[CH:8][CH:9]=1
Reactant: N#C[C@@H]1CCCN1C(=O)CNC12CC3CC1CC(c1ccc([N+](=O)[O-])cc1)(C3)C2
Agent: [Fe]
Agent: [Cl-]
Agent: [NH4+]
Solvent: CCO
Solvent: C1CCOC1
Solvent: O
Product: N#C[C@@H]1CCCN1C(=O)CNC12CC3CC1CC(c1ccc(N)cc1)(C3)C2
Temperature: 25 °C
Yield: 48.4 %

Procedure:
To a stirred solution of the compound obtained from example 29 (0.2 g, 0.51 mmol) in a 1:2:4 mixture of water, THF, and ethanol (7 mL) respectively was sequentially added solid NH4Cl (0.1 g, 1.87 mmol) and Fe powder (0.1 g, 1.78 mmol). The reaction mixture was heated to reflux for 2 h. After cooling the reaction mixture to room temperature, it was filtered through a small pad of celite and washed the bed with EtOAc. The filtrate was evaporated under reduced pressure and the residue was diluted with water and extracted with EtOAc. The combined organic layer was washed with water, dried over anhydrous Na2SO4, and the solvent was evaporated under reduced pressure to obtain (2S)-1-{N-[2-(4-aminophenyl)hexahydro-2,5-methanopentalen-3a(1H)-yl]glycyl}pyrrolidine-2-carbonitrile as off-white solid (0.09 g) in 50% yield. m/z (M+1) 365; 1H NMR (CDCl3) 300 MHz δ 7.05 (d, J=8.5 Hz, 2H), 6.63 (d, J=8.5 Hz, 2H), 4.90-4.75 (m, 1H), 3.80-3.40 (m, 4H), 2.45-1.70 (m, 15H), 1.65-1.57 (m, 1H).
Reaction SMILES: C([O:4][C@@H:5]1[C@H:12]2[C@H:8]([O:9][CH2:10][CH2:11]2)[O:7][CH2:6]1)(=O)C.C(=O)([O-])[O-].[K+].[K+]>CO>[O:7]1[C@H:8]2[O:9][CH2:10][CH2:11][C@H:12]2[C@@H:5]([OH:4])[CH2:6]1
Reactant: CC(=O)O[C@H]1CO[C@H]2OCC[C@H]21
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Product: O[C@H]1CO[C@H]2OCC[C@H]21
Temperature: 30 °C
Yield: 99.2 %

Procedure:
(3R,3aS,6aR)-Hexahydrofuro[2,3-b]furan-3-yl acetate (14.0 g) was dissolved in Methanol (42 ml). Potassium carbonate (0.34 g) was added to the reaction mass. Reaction mass was stirred at 25-35° C. till the completion of reaction. Reaction mass was concentrated to residue under vacuum at 40-45° C. Dichloromethane (42 ml) was charged to residue along with activated carbon (0.7 g) and stirred for 1 hr and then filtered through hyflow bed. Filtrate was concentrated to residue to get (3R,3aS,6aR)-Hexahydrofuro[2,3-b]furan-3-ol (Yield 10.5 g)
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[C:7]([CH2:9][CH2:10][CH3:11])[CH:6]=[CH:5][C:4]=1[CH2:12][CH2:13][CH3:14].[Br:15]N1C(=O)CCC1=O>C(#N)C.[Cl-].[Na+].O>[Br:15][C:6]1[CH:5]=[C:4]([CH2:12][CH2:13][CH3:14])[C:3]([O:2][CH3:1])=[CH:8][C:7]=1[CH2:9][CH2:10][CH3:11]
Reactant: CCCc1ccc(CCC)c(OC)c1
Reactant: O=C1CCC(=O)N1Br
Agent: [Cl-]
Agent: [Na+]
Solvent: CC#N
Solvent: O
Product: CCCc1cc(OC)c(CCC)cc1Br
Temperature: 60 °C
Reaction time: 20 h
Yield: 88.6 %

Procedure:
To a solution of 2-methoxy-1,4-dipropylbenzene (2.0 g, 10.4 mmol) in acetonitrile (30 mL) at room temperature was added N-bromosuccinimide (1.85 g, 10.4 mmol) in three portions. The solution was stirred at 60° C. for 20 hr and then most of the solvent was removed in vacuo. Extracton in hexanes (2×100 mL) with 50% saturated brine (75 mL) and flash chromatography with silica gel (100% hexanes) provided the title compound as a colorless liquid (2.50 g, 89% yield): 1H NMR (300 MHz, CDCl3) δ 0.93 (t, 3H, J=7.5 Hz), 0.99 (t, 3H, J=7.6 Hz), 1.60 (m, 4H), 2.50 (t, 2H, J=7.7 Hz), 2.65 (t, 2H, J=7.8 Hz), 3.79 (s, 3H), 6.67 (s, 1H), 7.24 (s, 1H).