Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH:1][C:2]1[C:7]2=[N:8][C:9]([CH3:13])=[CH:10][C:11](=[O:12])[N:6]2[CH:5]=[CH:4][CH:3]=1.C[O-].[Na+].[Br:17][C:18]1[CH:25]=[CH:24][CH:23]=[CH:22][C:19]=1[CH2:20]Br>C(O)C>[Br:17][C:18]1[CH:25]=[CH:24][CH:23]=[CH:22][C:19]=1[CH2:20][O:1][C:2]1[C:7]2=[N:8][C:9]([CH3:13])=[CH:10][C:11](=[O:12])[N:6]2[CH:5]=[CH:4][CH:3]=1
Reactant: BrCc1ccccc1Br
Reactant: Cc1cc(=O)n2cccc(O)c2n1
Agent: C[O-]
Agent: [Na+]
Solvent: CCO
Product: Cc1cc(=O)n2cccc(OCc3ccccc3Br)c2n1

Procedure:
To 35.2 g of 9-hydroxy-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one suspended in 100 ml of absolute ethanol is added a solution of 11.0 g of sodium methoxide in 165 ml of absolute ethanol. To this is then added 50.0 g o-bromobenzyl bromide dissolved in 25 ml of absolute ethanol. The mixture is then heated under reflux for about 6 hours and worked up to give 9-[(o-bromobenzyl)oxy]-2-methyl-4H-pyrido[1,2-a]-pyrimidin-4-one, m.p. 144°-146°, after recrystallization from ethyl acetate.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:14])[CH2:4][C:5]1[CH:10]=[CH:9][C:8]([N+:11]([O-])=O)=[CH:7][CH:6]=1.[H][H]>CO.CCOC(C)=O.[Pd]>[CH3:1][O:2][C:3](=[O:14])[CH2:4][C:5]1[CH:10]=[CH:9][C:8]([NH2:11])=[CH:7][CH:6]=1
Reactant: COC(=O)Cc1ccc([N+](=O)[O-])cc1
Reactant: [H][H]
Agent: [Pd]
Solvent: CCOC(C)=O
Solvent: CO
Product: COC(=O)Cc1ccc(N)cc1
Yield: 98.7 %

Procedure:
(4-Nitro-phenyl)-acetic acid methyl ester (1.08 g, 5.52 mmol) was dissolved in methanol (50 mL) and EtOAc (50 mL), then added to a Parr bottle containing 10% Pd/C (0.42 g), the vessel was subjected to hydrogen atmosphere (40 psi) for 2 h under the Parr Shaker Apparatus conditions. Workup with filtration via a glass membrane filter paper, solvent was removed under reduced pressure to afford (4-amino-phenyl)-acetic acid methyl ester as an oil (0.9 g, 98.7%). 1H NMR (CDCl3) δ 7.05 (d, 1H), 6.62 (d, 1H), 3.63 (s, 3H), 3.6 (bs, 2H) 3.5 (s, 2H).
Reaction SMILES: [C:1]1([C@@H:7]2[CH2:12][N:11](S(C3C=CC(C)=CC=3)(=O)=O)[CH2:10][CH2:9][N:8]2S(C2C=CC(C)=CC=2)(=O)=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C1(O)C=CC=CC=1.Br.C(OC(C)C)(C)C>O>[C:1]1([C@@H:7]2[CH2:12][NH:11][CH2:10][CH2:9][NH:8]2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: Cc1ccc(S(=O)(=O)N2CCN(S(=O)(=O)c3ccc(C)cc3)[C@H](c3ccccc3)C2)cc1
Agent: Br
Solvent: Oc1ccccc1
Solvent: CC(C)OC(C)C
Solvent: O
Product: c1ccc([C@@H]2CNCCN2)cc1
Temperature: 120 °C
Reaction time: 5 h
Yield: 66.7 %

Procedure:
A mixture of (R)-2-phenyl-1,4-bis(p-toluenesulphonyl)piperazine (10 g) and phenol (9.4 g) in 48% strength hydrobromic acid (100 cc) is heated with very vigorous stirring to a temperature in the region of 120° C. for 5 hours. After cooling to approximately 80° C., the reaction mixture is treated with water (250 cc), cooled to about 20° C. and washed with dichloromethane (5×100 cc). The aqueous phase is concentrated under reduced pressure (20 kPa) at approximately 80° C. The residue is taken up with ethyl acetate (100 cc), cooled to 5° C. and treated at between 5° and 20° C. with 30% strength aqueous sodium hydroxide (100 cc). The organic phase is separated and the aqueous phase extracted again with ethyl acetate (3×100 cc). The combined organic extracts are washed with 5N aqueous sodium hydroxide (4×20 cc), dried over magnesium sulphate, filtered and concentrated to dryness under reduced pressure (20 kPa) at approximately 30° C. The residue obtained is taken up with isopropyl ether (15 cc) at approximately 0° C., drained and washed at the same temperature with the same solvent (10 cc). (R)-2-Phenylpiperazine (2.3 g) is obtained in the form of a colorless solid, m.p. 117° C.
Reaction SMILES: C([O:8][C:9]1[C:14]2[N:15]([CH2:18][CH3:19])[CH:16]=[N:17][C:13]=2[CH:12]=[C:11]([Br:20])[CH:10]=1)C1C=CC=CC=1.B(Br)(Br)Br.C1COCC1.C(NCC)C>C(Cl)Cl.CO>[Br:20][C:11]1[CH:10]=[C:9]([OH:8])[C:14]2[N:15]([CH2:18][CH3:19])[CH:16]=[N:17][C:13]=2[CH:12]=1
Reactant: CCn1cnc2cc(Br)cc(OCc3ccccc3)c21
Agent: BrB(Br)Br
Solvent: ClCCl
Solvent: CCNCC
Solvent: C1CCOC1
Product: CCn1cnc2cc(Br)cc(O)c21
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a solution of 7-(benzyloxy)-5-bromo-1-ethyl-1H-benzo[d]imidazole (225 mg, 0.679 mmol) in DCM (8 mL) at 0° C. was added a solution of 1.0 M BBr3 in THF (0.66 mL, 1.5 equiv). After 1 h at 0° C., methanol (1.5 mL), and diethylamine (1.3 mL) were added to the reaction mixture, which was then stirred at rt for 1 h. Reaction mixture was then concentrated and water was added, the solids formed were filtered, washed with water and dried to give the title compound which was used further without purification. LCMS-ESI+ (m/z): [M+H]+ calcd for C9H10BrN2O: 241.0; found: 241.0.
Reaction SMILES: [Mn]([O-])(=O)(=O)=O.[K+].C(OC(=O)C)(=O)C.C([O-])(=O)C.[K+].C([O:22][C:23]([CH3:25])=[CH2:24])(=O)C.[C:26]1(=[O:32])[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]1>C(O)(=O)C.O>[CH2:24]([CH:27]1[CH2:28][CH2:29][CH2:30][CH2:31][C:26]1=[O:32])[C:23]([CH3:25])=[O:22]
Reactant: O=C1CCCCC1
Reactant: C=C(C)OC(C)=O
Agent: O=[Mn](=O)(=O)[O-]
Agent: CC(=O)[O-]
Agent: [K+]
Solvent: CC(=O)O
Solvent: CC(=O)OC(C)=O
Solvent: O
Product: CC(=O)CC1CCCCC1=O
Temperature: 70 °C

Procedure:
To a solution of manganic acetate in acetic acid, prepared in situ by the addition of 16 g. of potassium permanganate (0.1 m.) to 88 g. of manganous acetate dihydrate (Mn(OAc)2. 2H2O) (0.42 m.) in 570 milliliters of glacial acetic acid followed by 124 ml. of acetic anhydride and 60 g. of potassium acetate, were added 100 g. (1.0 m.) of isopropenyl acetate and 98 g. (1.0 m.) of cyclohexanone. The reaction mixture was heated under nitrogen to 70° C. until the brown manganic color disappeared. The reaction mixture was cooled, diluted with water, and extracted with ether. The product, 2-acetonyl-cyclohexanone ##STR84## was isolated by distillation, b.p. 70° C. at 0.05 mm. mercury, yield about 8 g. (20% based on Mn).
Reaction SMILES: Br[C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][N:3]=1.[N:10]1([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:15][CH2:14][NH:13][CH:12]([C:16]([O:18][CH3:19])=[O:17])[CH2:11]1.C(OC(C)(C)C)=O>>[C:6]([C:5]1[CH:8]=[CH:9][C:2]([N:13]2[CH2:14][CH2:15][N:10]([C:20]([O:22][C:23]([CH3:24])([CH3:25])[CH3:26])=[O:21])[CH2:11][CH:12]2[C:16]([O:18][CH3:19])=[O:17])=[N:3][CH:4]=1)#[N:7]
Reactant: COC(=O)C1CN(C(=O)OC(C)(C)C)CCN1
Reactant: N#Cc1ccc(Br)nc1
Agent: CC(C)(C)OC=O
Product: COC(=O)C1CN(C(=O)OC(C)(C)C)CCN1c1ccc(C#N)cn1
Yield: 36 %

Procedure:
This compound was synthesized from 6-bromonicotinonitrile and 1-tert-butyl 3-methyl piperazine-1,3-dicarboxylate as described for example 43 step 1 (200 mg, yield 36%). 1H NMR (400 MHz, CDCl3) δ 8.42 (d, J=2.3 Hz, 1H), 7.72-7.69 (dd, J=9.0 Hz, 2.3 Hz, 1H), 6.68 (d, J=9.0 Hz, 1H), 5.35 (m, 1H), 4.67-4.64 (d, J=13.6 Hz, 1H), 4.19 (m, 1H), 3.81-3.79 (d, J=9.8 Hz, 1H), 3.73 (s, 3H), 3.53-3.48 (m, 1H), 3.27-3.23 (m, 1H), 3.06 (m, 1H), 1.47 (s, 9H). MS (ESI) m/z: Calculated for C17H22N4O4: 346.16. found: 247.2 (M+H-Boc)+
Reaction SMILES: C[O:2][C:3]1[CH:4]=[C:5](/[CH:9]=[C:10]2/[CH:11]([N:16]3[CH2:19][CH2:18][CH2:17]3)[CH2:12][CH2:13][CH2:14][CH2:15]/2)[CH:6]=[CH:7][CH:8]=1.Br>O>[OH:2][C:3]1[CH:4]=[C:5]([CH:9]=[C:10]2[CH2:15][CH2:14][CH2:13][CH2:12][CH:11]2[N:16]2[CH2:19][CH2:18][CH2:17]2)[CH:6]=[CH:7][CH:8]=1
Reactant: COc1cccc(/C=C2\CCCCC2N2CCC2)c1
Agent: Br
Solvent: O
Product: Oc1cccc(C=C2CCCCC2N2CCC2)c1
Temperature: 95 °C
Yield: 76.9 %

Procedure:
A mixture of 1.1 g of (±)-(E)-N-[2[(3-methoxyphenyl)methylene]cyclohexyl]azetidine, prepared by analogy to the preparation of the 4-methoxy compound of Example 5, and 5 ml of 48% hydrogen bromide in water solution was stirred and heated at 95° C. for 2.75 hr. The resulting mixture was cooled and extracted with diethyl ether. The ether extract was dried with magnesium sulfate and evaporated to give 0.8 g of N-[2-[(3-hydroxyphenyl)methylene]cyclohexyl]azetidine as an oil which deposited as crystals upon standing overnight. Filtration with diethyl ether gave 0.21 g of this 3-hydroxyphenyl compound as a pale yellow solid. The UV, IR, mass spectrum and NMR analysis indicated the named product was present. Gas chromatography (GC) analysis indicated that this product was a mixture containing about 92% of (±)-(E)-1-[2-[(3-hydroxyphenyl)methylene]cyclohexyl]azetidine, mp 160°-165° C. and 8% of the starting 1-[2-(3-methoxyphenyl)methylene]cyclohexyl]azetidine, mp 136°-137° C.
Reaction SMILES: [CH2:1]([O:5][C:6]1[CH:31]=[CH:30][C:29]([O:32][CH2:33][CH:34]([CH3:36])[CH3:35])=[CH:28][C:7]=1[C:8]([C:10]1[CH:11]=[CH:12][C:13]([O:23][CH2:24][CH:25]([CH3:27])[CH3:26])=[C:14]([CH2:16][CH2:17][C:18]([O:20]CC)=[O:19])[CH:15]=1)=[O:9])[CH:2]([CH3:4])[CH3:3].[OH-].[Na+].C(Cl)(Cl)Cl.Cl>C(O)C.O>[CH2:1]([O:5][C:6]1[CH:31]=[CH:30][C:29]([O:32][CH2:33][CH:34]([CH3:36])[CH3:35])=[CH:28][C:7]=1[C:8]([C:10]1[CH:11]=[CH:12][C:13]([O:23][CH2:24][CH:25]([CH3:27])[CH3:26])=[C:14]([CH2:16][CH2:17][C:18]([OH:20])=[O:19])[CH:15]=1)=[O:9])[CH:2]([CH3:4])[CH3:3]
Reactant: CCOC(=O)CCc1cc(C(=O)c2cc(OCC(C)C)ccc2OCC(C)C)ccc1OCC(C)C
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: ClC(Cl)Cl
Solvent: CCO
Product: CC(C)COc1ccc(OCC(C)C)c(C(=O)c2ccc(OCC(C)C)c(CCC(=O)O)c2)c1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 99.8 %

Procedure:
In 26 ml of ethanol is dissolved 5.2 g of ethyl 3-[5-(2,5-diisobutoxybenzoyl)-2-isobutoxyphenyl]-propanoate. After adding 6 ml of 5 mol/L aqueous solution of sodium hydroxide, the mixture is stirred at ambient temperature for 30 minutes. Chloroform and water are added to the reaction mixture, pH is adjusted to 2 with 6 mol/L hydrochloric acid, and the organic layer is separated. The organic layer is washed with water and saturated aqueous solution of sodium chloride successively, and the solvent is distilled off from the reaction mixture under reduced pressure. Thus, 4.9 g of 3-[5-(2,5-diisobutoxybenzoyl)-2-isobutoxyphenyl]-propanoic acid is obtained as a yellow solid product.
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([Cl:8])[CH:5]=[C:4]([CH3:9])[N:3]=1.C1C(=O)N([I:17])C(=O)C1>>[Cl:8][C:6]1[C:5]([I:17])=[C:4]([CH3:9])[N:3]=[C:2]([NH2:1])[N:7]=1
Reactant: Cc1cc(Cl)nc(N)n1
Reactant: O=C1CCC(=O)N1I
Product: Cc1nc(N)nc(Cl)c1I

Procedure:
The title compound is synthesized according to general procedure GP1 starting from 10 g (70 mmol) 2-amino-4-chloro-6-methylpyrimidine and 16 g NIS (70 mmol). Yield: 18 g (95%). The crude product is used in next steps without further purification.
Reaction SMILES: C[Si](C)(C)[O-].[K+].[Br:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]([C:17]#[N:18])([CH3:16])[CH3:15])=[CH:10][CH:9]=1.[OH2:19]>C1(C)C=CC=CC=1>[NH2:18][C:17]([C:14]([C:11]1[CH:10]=[CH:9][C:8]([Br:7])=[CH:13][CH:12]=1)([CH3:16])[CH3:15])=[O:19]
Reactant: CC(C)(C#N)c1ccc(Br)cc1
Reactant: O
Agent: C[Si](C)(C)[O-]
Agent: [K+]
Solvent: Cc1ccccc1
Product: CC(C)(C(N)=O)c1ccc(Br)cc1
Temperature: 25 °C
Yield: 92 %

Procedure:
Potassium trimethylsilanolate (purity: 90%)(250 g, 1,800 mmol) was added at room temperature to a solution of 100 g (450 mmol) of 1-bromo-4-(1-cyano-1-methylethyl)benzene (referential compound 1-1) in 1,000 ml of toluene with stirring in an argon stream and the mixture was stirred for 4.5 hours under a condition of heating to reflux. After the reaction was finished, the reaction solution was cooled down to room temperature and 500 ml of water was dropped thereinto. The mixed solution was stirred for 25 minutes at room temperature and the resulting solid was filtered off and washed with 400 ml of water to give 99 g of the title compound as white powder (yield: 92%).
Reaction SMILES: COC1C=CC(C2CCC3C(=CC=C(OC)C=3)C2)=C(N)C=1.C[O:23][C:24]1[CH:25]=[CH:26][C:27]([CH:33]2[CH2:42][CH2:41][C:40]3[C:35](=[CH:36][CH:37]=[C:38]([O:43]C)[CH:39]=3)[CH2:34]2)=[C:28]([N:30]([CH3:32])[CH3:31])[CH:29]=1>>[CH3:31][N:30]([CH3:32])[C:28]1[CH:29]=[C:24]([OH:23])[CH:25]=[CH:26][C:27]=1[CH:33]1[CH2:42][CH2:41][C:40]2[CH:39]=[C:38]([OH:43])[CH:37]=[CH:36][C:35]=2[CH2:34]1
Reactant: COc1ccc2c(c1)CCC(c1ccc(OC)cc1N(C)C)C2
Agent: COc1ccc(C2CCc3cc(OC)ccc3C2)c(N)c1
Product: CN(C)c1cc(O)ccc1C1CCc2cc(O)ccc2C1
Yield: 87.9 %

Procedure:
Synthesized from 5-methoxy-2-(6-methoxy-1,2,3,4-tetrahydronaphthalen-2-yl)phenylamine according to an analogous synthetic method to Preparation Example 18, [5-methoxy-2-(6-methoxy-1,2,3,4-tetrahydronaphthalen-2-yl)phenyl]dimethylamine (120 mg) was used according to an analogous synthetic method to Example 364 described below to provide the title compound (96 mg).
Reaction SMILES: Br[C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[CH:9][CH:8]=[CH:7]2.[Li]CCCC.[C:17]1(=O)[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[CH2:19][CH2:18]1.Cl>C1COCC1>[N:10]1[C:11]2[C:6](=[CH:5][CH:4]=[CH:3][C:2]=2[CH:17]2[C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[CH:19]=[CH:18]2)[CH:7]=[CH:8][CH:9]=1
Reactant: Brc1cccc2cccnc12
Reactant: O=C1CCc2ccccc21
Agent: Cl
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: C1=CC(c2cccc3cccnc23)c2ccccc21
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 54.3 %

Procedure:
10.4 g (50 mmol) of 8-bromoquinoline in 100 ml of THF were cooled to about −100° C. 20 ml of n-BuLi (2.5M in hexane, 50 mmol) were added dropwise within a period of 5 min while the internal temperature was held below −80° C. After this addition stirring was continued at −80° C. for a further 15 min, and 6.6 g of 1-indanone (50 mmol) dissolved in 30 ml of THF were then added dropwise within a period of 10 min. The reaction mixture was then allowed to reach room temperature gradually and was then heated for 3 b at reflux. Once the mixture had cooled to room temperature, ice was added, followed by hydrochloric acid until the pH was about 1, followed by stirring for 30 min. The aqueous and organic phase were separated. The aqueous phase was mixed with ammonia solution until the pH was about 9 and extracted with ether. The combined organic phases were then evaporated to dryness in vacuo. The resultant viscous oil (1-(8-quinolyl)indan-1-ol (8H2O)) vas mixed with hydrochloric acid until the pH was 0, heated at reflux for 2 hours and then neutralised. After work-up and drying it was possible to isolate 6.6 g of 1-(8-quinolyl)indene (55%) as a colorless solid.
Reaction SMILES: [NH2:1][C@H:2]([C:7]([OH:9])=[O:8])[C:3]([CH3:6])([CH3:5])[CH3:4].[C:10](Cl)(=[O:17])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1>>[C:10]([NH:1][CH:2]([C:3]([CH3:6])([CH3:5])[CH3:4])[C:7]([OH:9])=[O:8])(=[O:17])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1
Reactant: CC(C)(C)[C@H](N)C(=O)O
Reactant: O=C(Cl)c1ccccc1
Product: CC(C)(C)C(NC(=O)c1ccccc1)C(=O)O

Procedure:
Racemic tert-butylglycine and benzoyl chloride were processed as described in Example 26A to provide the desired product.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:11]=[CH:12][C:13]=1[CH:14]([CH3:28])[C:15]([C:21]1[CH:26]=[CH:25][N:24]=[C:23]([Cl:27])[CH:22]=1)([OH:20])[C:16]([F:19])([F:18])[F:17])[CH2:5]OS(C)(=O)=O.[C-:29]#[N:30].[Na+]>CN(C=O)C.C(OCC)(=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([CH2:5][C:29]#[N:30])[CH:11]=[CH:12][C:13]=1[CH:14]([CH3:28])[C:15]([C:21]1[CH:26]=[CH:25][N:24]=[C:23]([Cl:27])[CH:22]=1)([OH:20])[C:16]([F:19])([F:18])[F:17]
Reactant: CC(c1ccc(COS(C)(=O)=O)cc1Cl)C(O)(c1ccnc(Cl)c1)C(F)(F)F
Reactant: [C-]#N
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CC(c1ccc(CC#N)cc1Cl)C(O)(c1ccnc(Cl)c1)C(F)(F)F
Temperature: 85 °C
Reaction time: 1.5 h
Yield: 60.7 %

Procedure:
Methanesulfonic acid 3-chloro-4-[2-(2-chloro-pyridin-4-yl)-3,3,3-trifluoro-2-hydroxy-1-methyl-propyl]-benzyl ester (66 mg) was dissolved in DMF at RT under argon. Sodium cyanide (18 mg) was added and the mixture was warmed to 85° C. and allowed to stir for 1.5 hours. The mixture was diluted with ethyl acetate and washed with water and brine. The organic extracts were dried over Na2SO4 and evaporated. The residue was purified by flash chromatography (silica gel, gradient of ethyl acetate in heptane) to give the desired compound as a colorless solid (34 mg). MS (m/e)=389.1 (MH+).
Reaction SMILES: [NH2:1][CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[CH2:9][C:10]([OH:12])=[O:11].[Li].C(N(CC)CC)C>C(O)(C)(C)C>[NH2:1][CH2:2][C:3]1[CH2:8][CH:7]=[CH:6][CH2:5][C:4]=1[CH2:9][C:10]([OH:12])=[O:11]
Reactant: NCc1ccccc1CC(=O)O
Agent: [Li]
Solvent: CCN(CC)CC
Solvent: CC(C)(C)O
Product: NCC1=C(CC(=O)O)CC=CC1

Procedure:
The procedure used by Welch, Dolfini and Giarrusso in U.S. Pat. 3,720,665 (Example 1) to make D-2-amino-2-(1,4-cyclohexadienyl)acetic acid was adapted. A solution of 830 ml. of distilled liquid ammonia was dried with 40 mg. of lithium under an argon atmosphere. To this stirred solution was added 11.0 g. (0.07 mole) of 2 -aminomethylphenylacetic acid and 340 ml. of tert. butyl alcohol. A total of 1.6 g. (0.225 mole) of lithium was added to the vigorously stirred solution over a period of 2 hours. The grey mixture was then treated with 35 g. (0.215 mole) of triethylamine (TEA) hydrochloride and stirred overnight at room temperature for 18 hours. The tert. butyl alcohol was removed at 40° (15 mm.) to yield a white residue which was dried in vacuo over P2O5 overnight. The solid was dissolved in 30 ml. of 1:1 methanol-water and added with stirring to 3.5 l. of 1:1 chloroform-acetone at 5°. the mixture was stirred for 20 min. and the amino acid α-(2-aminomethyl-1,4-cyclohexadienyl)acetic acid, was collected and dried for 16 hours in vacuo over P2O5 to yield 6.3 g. (58%) of white crystals, m.p. 190° decomp. The IR and NMR spectra were consistent for the structure.
Reaction SMILES: [OH:1][C:2]1[N:6]([C:7]2[CH:12]=[C:11]([C:13]#[N:14])[CH:10]=[CH:9][N:8]=2)[N:5]=[CH:4][CH:3]=1.[CH:15]1([C:18]2[CH:23]=[CH:22][C:21]([CH2:24]O)=[CH:20][C:19]=2[F:26])[CH2:17][CH2:16]1>>[CH:15]1([C:18]2[CH:23]=[CH:22][C:21]([CH2:24][O:1][C:2]3[N:6]([C:7]4[CH:12]=[C:11]([C:13]#[N:14])[CH:10]=[CH:9][N:8]=4)[N:5]=[CH:4][CH:3]=3)=[CH:20][C:19]=2[F:26])[CH2:17][CH2:16]1
Reactant: OCc1ccc(C2CC2)c(F)c1
Reactant: N#Cc1ccnc(-n2nccc2O)c1
Product: N#Cc1ccnc(-n2nccc2OCc2ccc(C3CC3)c(F)c2)c1

Procedure:
The title compound was prepared from 2-(5-hydroxy-1H-pyrazol-1-yl)pyridine-4-carbonitrile and (4-cyclopropyl-3-fluorophenyl)methanol according to the procedure for the preparation of Example 39, part C. 1H NMR (400 MHz, CDCl3): δ 0.71-0.75 (2H, m), 0.96-1.02 (2H, m), 2.06-2.10 (1H, m), 5.17 (2H, s), 5.72 (1H, d, J=1.6 Hz), 6.88-6.92 (1H, m), 7.07-7.10 (2H, m), 7.40 (1H, dd, J=1.6 Hz, 5.2 Hz), 7.55 (1H, d, J=2.0 Hz), 8.02 (1H, s), 8.70 (1H, d, J=5.2 Hz). [M+H] Calc'd for C19H15FN4O, 335; Found, 335.
Reaction SMILES: C(OC([N:8]1[CH2:12][C@@H:11]([F:13])[CH2:10][C@H:9]1[C:14](=[O:16])[NH2:15])=O)(C)(C)C.[ClH:17].C(OCC)(=O)C>C(OCC)(=O)C>[ClH:17].[C:14]([C@@H:9]1[CH2:10][C@H:11]([F:13])[CH2:12][NH:8]1)(=[O:16])[NH2:15]
Reactant: CC(C)(C)OC(=O)N1C[C@@H](F)C[C@H]1C(N)=O
Agent: Cl
Solvent: CCOC(C)=O
Product: NC(=O)[C@@H]1C[C@H](F)CN1

Procedure:
(2S,4S)-1-(tert-Butoxycarbonyl)-2-carbamoyl-4-fluoropyrrolidine (122 g) was suspended in ethyl acetate (400 mL). While stirring this suspension under ice cooling, 4 mol/L hydrochloric acid-ethyl acetate (525 mL) was slowly added dropwise. After stirring at ice-cold temperature for 30 minutes and at room temperature for 3 hours, the precipitated crystal was collected by filtration to give the titled compound (85.9 g, white powder).
Reaction SMILES: [CH2:1]([NH2:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.[CH3:16][C:17]1[C:18]2[CH:38]=[CH:37][C:36](=[O:39])[N:35]([C:40]3[CH:48]=[CH:47][C:43]([C:44](Cl)=[O:45])=[CH:42][CH:41]=3)[C:19]=2[N:20]=[C:21]([N:23]2[CH2:28][CH2:27][N:26]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[CH2:25][CH2:24]2)[N:22]=1>C(Cl)Cl.O>[CH2:1]([NH:8][C:44](=[O:45])[C:43]1[CH:47]=[CH:48][C:40]([N:35]2[C:19]3[N:20]=[C:21]([N:23]4[CH2:24][CH2:25][N:26]([C:29]5[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=5)[CH2:27][CH2:28]4)[N:22]=[C:17]([CH3:16])[C:18]=3[CH:38]=[CH:37][C:36]2=[O:39])=[CH:41][CH:42]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: Cc1nc(N2CCN(c3ccccc3)CC2)nc2c1ccc(=O)n2-c1ccc(C(=O)Cl)cc1
Reactant: NCc1ccccc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Solvent: O
Product: Cc1nc(N2CCN(c3ccccc3)CC2)nc2c1ccc(=O)n2-c1ccc(C(=O)NCc2ccccc2)cc1
Reaction time: 2 h
Yield: 78.2 %

Procedure:
To a solution of benzylamine (0.0536 g; 0.50mmol) and a drop of triethylamine in 5 mL of methylene chloride, compound L (0.043 g; 0.094 mmol) in 3 mL of methylene chloride was added at room temperature. The reaction mixture was stirred for 2 h and then diluted with 10 mL of methylene chloride and 10 mL of water. The organic phase was dried over CaCl2, concentrated and the crude reaction mixture purified by silica gel column chromatography (eluant: CH2Cl2/CH3OH=190/10) to yield compound 15 (0.039 g; 78%).
Reaction SMILES: [CH2:1]([NH2:4])[CH:2]=[CH2:3].C1C2NC3C(=CC=CC=3)SC=2C=CC=1.[CH2:19]([O:21][SiH:22]([O:26][CH2:27][CH3:28])[O:23][CH2:24][CH3:25])[CH3:20]>>[NH2:4][CH2:1][CH2:2][CH2:3][Si:22]([O:26][CH2:27][CH3:28])([O:23][CH2:24][CH3:25])[O:21][CH2:19][CH3:20]
Reactant: C=CCN
Reactant: CCO[SiH](OCC)OCC
Agent: c1ccc2c(c1)Nc1ccccc1S2
Product: CCO[Si](CCCN)(OCC)OCC
Yield: 65 %

Procedure:
571 parts of allylamine, 0.38 part of [Rh(NBD)2 ](+). BF4(-) (note: NBD: Norbornadiene), 1.0 part of phenothiazine and 1640 parts of triethoxysilane were charged into a sealed tube and allowed to react in an oil bath for 2 hours at 130° C. Following cooling, the product was analyzed with gas chromatography. Aminopropyltriethoxysilane was produced at a yield of 65% and moreover, the ratio of γ:β isomer was 24:1.
Reaction SMILES: [Br:1][C:2]1[C:3]([CH3:13])=[CH:4][C:5]([O:11][CH3:12])=[C:6]([CH:10]=1)[C:7]([OH:9])=O.ON1C2C=CC=CC=2N=N1.[NH2:24][C:25]1[CH:34]=[CH:33][CH:32]=[C:31]2[C:26]=1[CH2:27][CH2:28][N:29]([CH3:35])[CH2:30]2>CN(C=O)C>[CH3:35][N:29]1[CH2:28][CH2:27][C:26]2[C:31](=[CH:32][CH:33]=[CH:34][C:25]=2[NH:24][C:7](=[O:9])[C:6]2[CH:10]=[C:2]([Br:1])[C:3]([CH3:13])=[CH:4][C:5]=2[O:11][CH3:12])[CH2:30]1
Reactant: COc1cc(C)c(Br)cc1C(=O)O
Reactant: CN1CCc2c(N)cccc2C1
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Product: COc1cc(C)c(Br)cc1C(=O)Nc1cccc2c1CCN(C)C2
Temperature: 25 °C
Yield: 53.9 %

Procedure:
5-Bromo-2-methoxy-4-methylbenzoic acid (0.245 g, 1 mmol), 1-(3-dimethyl-aminopropyl)-3-ethylcarbodiimide hydrochloride (0.200 g, 1 mmol) and 1-hydroxy-benzotriazole (0.155 g, 1 mmol) were dissolved in dry DMF (10 ml) and stirred at room temperature under argon for 25 mins before 5-amino-2-methyl-1,2,3,4-tetrahydroisoquinoline (0.163 g, 1 mmol) was added. The mixture was then stirred for 24 under argon at room temperature. The DMF was removed in vacuo and the residue suspended in ethyl acethate and washed with water. The insoluble white precipithate was filtered off, washed with water then dried to afford the title compound (210 mg).
Reaction SMILES: [CH2:1]([C:12]1[N:16]=[C:15]([C:17]2[CH:24]=[CH:23][C:20]([CH:21]=O)=[CH:19][CH:18]=2)[O:14][N:13]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH3:11].[F:25][C:26]([F:36])([F:35])[C:27]1[CH:34]=[CH:33][CH:32]=[CH:31][C:28]=1[CH2:29][NH2:30]>>[F:25][C:26]([F:35])([F:36])[C:27]1[CH:34]=[CH:33][CH:32]=[CH:31][C:28]=1[CH2:29][NH:30][CH2:21][C:20]1[CH:23]=[CH:24][C:17]([C:15]2[O:14][N:13]=[C:12]([CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH3:11])[N:16]=2)=[CH:18][CH:19]=1
Reactant: NCc1ccccc1C(F)(F)F
Reactant: CCCCCCCCCCCc1noc(-c2ccc(C=O)cc2)n1
Product: CCCCCCCCCCCc1noc(-c2ccc(CNCc3ccccc3C(F)(F)F)cc2)n1

Procedure:
The same procedure as employed in the preparation of Example 357 (step a) but using 4-(3-undecyl-1,2,4-oxadiazol-5-yl)benzaldehyde and 2-(trifluoromethyl)benzylamine gave the title compound as an oil. M+(LC/MS(ESI)): 488.5. HPLC (Condition A), Rt: 4.78 min (HPLC purity: 95.4%).