Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[C:2]1[CH:11]=[C:10]2[C:5]([C:6](=[O:23])[C:7]([C:20]([OH:22])=[O:21])=[CH:8][N:9]2[C:12]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][C:13]=2[F:19])=[CH:4][C:3]=1[F:24].FOBOF.[CH3:30][N:31]1[CH2:36][CH:35]2[CH2:37][CH:32]1[CH2:33][NH:34]2.C(N(CC)CC)C>FB(O)O.CS(C)=O.O>[F:24][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:2]=1[N:34]1[CH2:33][CH:32]3[CH2:37][CH:35]1[CH2:36][N:31]3[CH3:30])[N:9]([C:12]1[CH:17]=[CH:16][C:15]([F:18])=[CH:14][C:13]=1[F:19])[CH:8]=[C:7]([C:20]([OH:22])=[O:21])[C:6]2=[O:23]
Reactant: O=C(O)c1cn(-c2ccc(F)cc2F)c2cc(Cl)c(F)cc2c1=O
Reactant: CN1CC2CC1CN2
Agent: FOBOF
Agent: OB(O)F
Solvent: O
Solvent: CCN(CC)CC
Solvent: CS(C)=O
Product: CN1CC2CC1CN2c1cc2c(cc1F)c(=O)c(C(=O)O)cn2-c1ccc(F)cc1F
Reaction time: 1 h
Yield: 18.8 %

Procedure:
15 g (37.36 m Mol) of the mixed anhydride of 7-chloro-6-fluoro-1-(2,4-difluorophenyl)-1,4-dihydro-4-oxoquinoline-3-carboxylic acid and difluoroboronic acid (obtained by heating 7-chloro-6-fluoro-1-(2.4-difluoro- phenyl)-1,4-dihycho-4-oxoquinoline-3-carboxylic acid in 60% aqueous fluoroboronic acid 15.36 g (56 m Mol) of the dihydrobromide of 2-methyl-2,5-diazabicyclo-(2.2.1)heptane and 31 ml (0.224 mol) triethylamine was stirred in 200 ml of dry DMSO at room temperature for 6 days. Then the reaction mixture was poured into 800 ml of cold water and the resultant precipitate collected by filtration washed with water and then heated to reflux with stirring in a mixture of 100 ml dioxane and 150 ml 3N NaOH for 1 hr. After cooling and with stirring, 500 ml of conc. HCl was added. After stirring for 1 hr., the undissolved material was removed by filtration, to give a clear solution which was extracted multiple times with methylene chloride. The aqueous phase was cooled in an ice bath and brought to pH 7.4 by the addition of dilute NaOH. The resultant was extracted with chloroform and the chloroform phase dried over sodium sulfate and the chloroform removed in vacuo, the resulting dark brown oil was recrystallized from 450 ml ethanol to give 3.15 g (18.8%) of the product as a hydrate, mp 215° C.-220° C. dec.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:13]2[CH:18]=[CH:17][C:16]([OH:19])=[C:15]([CH3:20])[CH:14]=2)([CH2:11][CH3:12])[CH2:9][CH3:10])=[CH:4][CH:3]=1.CC#N.C([O-])([O-])=O.[K+].[K+].[CH2:30](Br)[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1>CCOCC>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:13]2[CH:18]=[CH:17][C:16]([O:19][CH2:30][C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)=[C:15]([CH3:20])[CH:14]=2)([CH2:11][CH3:12])[CH2:9][CH3:10])=[CH:4][CH:3]=1
Reactant: BrCc1ccccc1
Reactant: CCC(CC)(c1ccc(Br)cc1)c1ccc(O)c(C)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Solvent: CCOCC
Product: CCC(CC)(c1ccc(Br)cc1)c1ccc(OCc2ccccc2)c(C)c1
Reaction time: 20 h
Yield: 82.5 %

Procedure:
To a solution of 4-[1-(4-bromophenyl)-1-ethylpropyl]-2-methylphenol (2.1 g, 6.3 mmol) in anhyd MeCN (30 mL) added anhyd K2CO3 (2.9 g, 21 mmol) and benzyl bromide (0.83 mL, 7.0 mmol). The reaction mixture was heated at reflux. After 20 h, the reaction mixture was cooled, diluted with Et2O (100 mL) and filtered. The filtrate was washed with H2O (2×50 mL) and brine, dried (anhyd Na2SO4), concentrated under reduced pressure and chromatographed (silica, EtOAC/Hex, 0:100 to 15:85) to give 5-[1-(4-bromophenyl)-1-ethylpropyl]-2-benzyloxytoluene (2.2 g, 82%), as a colorless liquid: 1H-NMR (CDCl3) δ 7.43-7.48 (2H, m), 7.31-7.42 (5H, m), 7.06 (2H, d, J=8.6), 6.94 (1H, dd, J=2.3, 8.3), 6.89 (1H, d, J=2.3), 6.79 (1H, d, J=8.3), 5.05 (2H, s), 4.23 (1H, s), 2.23 (3H, s), 2.05 (4H, q, J=7.3), 0.62 (6H, t, J=7.3).
Reaction SMILES: [C:1]1([CH:7]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH2:8][CH2:9][N:10]2[CH2:15][CH2:14][N:13]([C:16]3[C:17]([CH3:25])=[C:18]([CH:22]=[CH:23][CH:24]=3)[C:19](O)=[O:20])[CH2:12][CH2:11]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH:32]([NH:35][CH:36]1[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37]1)([CH3:34])[CH3:33]>>[CH:36]1([N:35]([CH:32]([CH3:34])[CH3:33])[C:19](=[O:20])[C:18]2[CH:22]=[CH:23][CH:24]=[C:16]([N:13]3[CH2:12][CH2:11][N:10]([CH2:9][CH2:8][CH:7]([C:1]4[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=4)[C:26]4[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=4)[CH2:15][CH2:14]3)[C:17]=2[CH3:25])[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37]1
Reactant: Cc1c(C(=O)O)cccc1N1CCN(CCC(c2ccccc2)c2ccccc2)CC1
Reactant: CC(C)NC1CCCCC1
Product: Cc1c(C(=O)N(C(C)C)C2CCCCC2)cccc1N1CCN(CCC(c2ccccc2)c2ccccc2)CC1

Procedure:
Step (d) of Example 1 was repeated, except that the compound prepared just above in step (c) was used instead of 3-[4-(3,3-diphenyl-1-propyl)piperazin-1-yl]-2-methylbenzoic acid and N-isopropylcyclohexylamine was used instead of N-methylbenzylamine. Thus, the title compound was prepared.
Reaction SMILES: N#N.[C:3]([SiH2:7][O:8][C:9]([CH3:23])([CH3:22])[C:10]1[O:11][CH:12]=[C:13]([CH2:15][N:16]2[N:20]=[C:19]([NH2:21])[CH:18]=[N:17]2)[N:14]=1)([CH3:6])([CH3:5])[CH3:4].CCN(C(C)C)C(C)C.[CH:33]1[CH:38]=[C:37]([CH2:39][O:40][C:41](Cl)=[O:42])[C:36]([Cl:44])=[CH:35][CH:34]=1>C(Cl)Cl.O>[Cl:44][C:36]1[CH:35]=[CH:34][CH:33]=[CH:38][C:37]=1[CH2:39][O:40][C:41](=[O:42])[NH:21][C:19]1[CH:18]=[N:17][N:16]([CH2:15][C:13]2[N:14]=[C:10]([C:9]([CH3:23])([CH3:22])[O:8][SiH2:7][C:3]([CH3:6])([CH3:4])[CH3:5])[O:11][CH:12]=2)[N:20]=1
Reactant: CC(C)(C)[SiH2]OC(C)(C)c1nc(Cn2ncc(N)n2)co1
Reactant: O=C(Cl)OCc1ccccc1Cl
Agent: N#N
Solvent: CCN(C(C)C)C(C)C
Solvent: O
Solvent: ClCCl
Product: CC(C)(C)[SiH2]OC(C)(C)c1nc(Cn2ncc(NC(=O)OCc3ccccc3Cl)n2)co1
Temperature: 0 °C
Reaction time: 1 h

Procedure:
In a flame dried round-bottomed flask equipped with a magnetic stir bar and under inert atmosphere (N2), a solution of 2-[2-(tert-butyl-dimethyl-silanyloxymethyl)-oxazol-4-ylmethyl]-2H-[1,2,3]triazol-4-ylamine (93 mg, 0.30 mmol) in CH2Cl2 (5.0 mL) was treated with DIPEA (0.08 mL, 0.48 mmol) followed by 2-chlorobenzylchloroformate (0.06 mL, 0.39 mmol) at 0° C. The reaction mixture was stirred at 0° C. for 1 h and water (5.0 mL) was added. The layers were separated and the aq. layer extracted with CH2Cl2 (2×10 mL). The combined org. extracts were dried over Na2SO4, filtered, and the solvent was removed under reduced pressure. Purification of the residue by FC (9:1 to 1:1 hept-EA) gave the title compound as an orange solid. TLC:rf (1:1 hept-EA)=0.27. LC-MS-conditions 01: tR=1.11 min; [M+H]+=478.01.
Reaction SMILES: [F:1][C:2]([F:13])([F:12])[C:3]1[CH:4]=[C:5](B(O)O)[CH:6]=[CH:7][CH:8]=1.[CH2:14]([O:16][C:17](=[O:36])[C:18]1[CH:23]=[C:22]([C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([C:30]([F:33])([F:32])[F:31])[CH:25]=2)[C:21]([OH:34])=[C:20]([Br:35])[CH:19]=1)[CH3:15]>>[CH2:14]([O:16][C:17](=[O:36])[C:18]1[CH:23]=[C:22]([C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([C:30]([F:33])([F:32])[F:31])[CH:25]=2)[C:21]([OH:34])=[C:20]([Br:35])[CH:19]=1)[CH3:15].[CH2:14]([O:16][C:17](=[O:36])[C:18]1[CH:19]=[C:20]([C:5]2[CH:6]=[CH:7][CH:8]=[C:3]([C:2]([F:13])([F:12])[F:1])[CH:4]=2)[C:21]([OH:34])=[C:22]([C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([C:30]([F:32])([F:31])[F:33])[CH:25]=2)[CH:23]=1)[CH3:15]
Reactant: OB(O)c1cccc(C(F)(F)F)c1
Agent: CCOC(=O)c1cc(Br)c(O)c(-c2cccc(C(F)(F)F)c2)c1
Product: CCOC(=O)c1cc(-c2cccc(C(F)(F)F)c2)c(O)c(-c2cccc(C(F)(F)F)c2)c1

Procedure:
3-Bromo-4-hydroxy-5(m-trifluoromethylphenyl)-benzoic acid ethyl ester and 3,5-bis-(m-trifluoromethylphenyl)-4-hydroxy-benzoic acid ethyl ester were prepared as white solids (2.445 g, 34% and 2.811 g, 33%, respectively) from 3-bromo-4-hydroxy-5-iodobenzoic and 3-trifluoromethyl-phenyl boronic acid using a procedure similar to step 1 of Example 175. 3-Bromo-4-hydroxy-5(m-trifluoromethylphenyl)-benzoic acid ethyl ester 1H NMR (CDCT3) δ 8.22 (d, 1H); 7.98 (d, 1H); 7.74 (s, 1H); 7.70 (d, 1H); 7.68-7.53 (m, 2H); 6.10 (s, 1H); 4.38 (q, 2H); 1.40 (t, 3H); 3,5-bis-(m-trifluoromethylphenyl)-4-hydroxy-benzoic acid ethyl ester ester 1H NMR (CDCl3) δ 8.02 (s, 2H); 7.84 (bs, 2H); 7.77-7.60 (m, 6H); 5.67 (s, 1H); 4.38 (q, 2H); 1.40 (t, 3H).
Reaction SMILES: ClC(N(C)C)=C(C)C.[C:9]1([C:19]([OH:21])=O)[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[CH:12]=[CH:11][CH:10]=1.[CH2:22]([C@@H:29]1[CH2:34][C@@H:33]([N:35]([CH2:42][C:43]2[C:52]3[C:47](=[CH:48][CH:49]=[CH:50][CH:51]=3)[N:46]=[CH:45][CH:44]=2)[C:36](=[O:41])[C:37]([F:40])([F:39])[F:38])[CH2:32][CH2:31][NH:30]1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.C(N(CC)CC)C>C(Cl)Cl.O>[CH2:22]([C@@H:29]1[CH2:34][C@@H:33]([N:35]([CH2:42][C:43]2[C:52]3[C:47](=[CH:48][CH:49]=[CH:50][CH:51]=3)[N:46]=[CH:45][CH:44]=2)[C:36](=[O:41])[C:37]([F:39])([F:40])[F:38])[CH2:32][CH2:31][N:30]1[C:19]([C:9]1[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[CH:12]=[CH:11][CH:10]=1)=[O:21])[C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1
Reactant: O=C(O)c1cccc2ccccc12
Reactant: O=C(N(Cc1ccnc2ccccc12)[C@H]1CCN[C@H](Cc2ccccc2)C1)C(F)(F)F
Agent: CC(C)=C(Cl)N(C)C
Solvent: ClCCl
Solvent: O
Solvent: CCN(CC)CC
Product: O=C(c1cccc2ccccc12)N1CC[C@H](N(Cc2ccnc3ccccc23)C(=O)C(F)(F)F)C[C@H]1Cc1ccccc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
92 μl (0.655 mmol) of 1-chloro-N,N,2-trimethyl-1-propen-1-amine are added to a solution of 96 mg (0.561 mmol) of 1-naphthoic acid in 2 ml of dry, methylene chloride at 0°, and the mixture is stirred at 0° for 1 hour and at room temperature for 1 hour. Subsequently a solution of 200 mg (0.468 mmol) of (2R*,4S*)-2-benzyl-N-(4-quinolylmethyl)-N-trifluoroacetyl-4-piperidinamine and 130 μl (0.936 mmol) of triethylamine in 3 ml of methylene chloride is added dropwise over the course of 10 minutes to this yellow solution at room temperature. After stirring at room temperature for 3 hours, water is added, the organic phase is separated off and washed twice more with water. The organic phases are dried over magnesium sulfate and evaporated to dryness. The yellow oil is chromatographed on silica gel with methylene chloride/methanol/conc. ammonia (800:50:1). The title compound is obtained as yellow oil. TLC: methylene chloride/methanol/conc. ammonia (700:50:1) Rf =0.49, FD-MS: M+ =581.
Reaction SMILES: [CH3:1][N:2]1[C:7]2[N:8]=[C:9](S(C)(=O)=O)[N:10]=[CH:11][C:6]=2[CH:5]=[CH:4][C:3]1=[O:16].[CH2:17]([NH2:19])[CH3:18]>>[CH2:17]([NH:19][C:9]1[N:10]=[CH:11][C:6]2[CH:5]=[CH:4][C:3](=[O:16])[N:2]([CH3:1])[C:7]=2[N:8]=1)[CH3:18]
Reactant: CCN
Reactant: Cn1c(=O)ccc2cnc(S(C)(=O)=O)nc21
Product: CCNc1ncc2ccc(=O)n(C)c2n1
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 82 %

Procedure:
A mixture of 8-methyl-2-methanesulfonyl-8H-pyrido[2,3-d]pyrimidin-7-one (152 mg, 0.63 mmol) in 2.5 mL of 70% aqueous ethylamine was stirred at room temperature for 10 minutes. The reaction mixture was partitioned between ethyl acetate and water, and the organic layer was washed with saturated sodium bicarbonate and brine, dried over magnesium sulfate, and concentrated in vacuo to give 105 mg (82%) of 2-ethylamino 8-methyl-8H-pyrido[2,3-d]pyrimidin-7-one, mp 194-195° C.
Reaction SMILES: Cl.[F:2][C:3]([F:12])([F:11])[C:4]1[CH:8]=[C:7]([CH2:9][NH2:10])[NH:6][N:5]=1.[F:13][C:14]1[CH:15]=[C:16]([CH:25]([CH3:29])[C:26](O)=[O:27])[CH:17]=[CH:18][C:19]=1[CH2:20][S:21]([CH3:24])(=[O:23])=[O:22].F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.ON1C2C=CC=CC=2N=N1.C(N(C(C)C)C(C)C)C>C1COCC1>[F:13][C:14]1[CH:15]=[C:16]([CH:25]([CH3:29])[C:26]([NH:10][CH2:9][C:7]2[NH:6][N:5]=[C:4]([C:3]([F:2])([F:11])[F:12])[CH:8]=2)=[O:27])[CH:17]=[CH:18][C:19]=1[CH2:20][S:21]([CH3:24])(=[O:22])=[O:23]
Reactant: NCc1cc(C(F)(F)F)n[nH]1
Reactant: CC(C(=O)O)c1ccc(CS(C)(=O)=O)c(F)c1
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: Cl
Agent: F[B-](F)(F)F
Solvent: C1CCOC1
Solvent: CCN(C(C)C)C(C)C
Product: CC(C(=O)NCc1cc(C(F)(F)F)n[nH]1)c1ccc(CS(C)(=O)=O)c(F)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 85.7 %

Procedure:
To a stirred solution of (3-(trifluoromethyl)-1H-pyrazol-5-yl)methanamine hydrochloride (194 mg, 0.96 mmol) and 2-(3-fluoro-4-(methylsulfonylmethyl)phenyl)propanoic acid (250 mg, 0.96 mmol) in THF (7.4 mL) were added O-(1H-benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluorborat (308 mg, 0.96 mmol), 1-hydroxybenzotriazole (135 mg, 0.96 mmol) and N-ethyldiisopropylamine (0.491 mL, 2.881 mmol). The reaction mixture was stirred for overnight at room temperature, concentrated in vacuo, purified by CC (eluent: ethyl acetate/cyclohexane (9:1)) to give 2-(3-fluoro-4-(methylsulfonylmethyl)phenyl)-N-((3-(trifluoromethyl)-1H-pyrazol-5-yl)methyl)propanamide (335 mg, 86%).
Reaction SMILES: [Cl-].[Al+3].[Cl-].[Cl-].[O:5]([C:12]1[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=1)[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.[CH2:19]1[O:22][CH:20]1[CH3:21]>C(O[Ti](OC(C)C)(OC(C)C)OC(C)C)(C)C>[O:5]([C:12]1[CH:13]=[CH:14][C:15]([O:18][CH2:19][C@@H:20]([OH:22])[CH3:21])=[CH:16][CH:17]=1)[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1
Reactant: CC1CO1
Reactant: Oc1ccc(Oc2ccccc2)cc1
Agent: CC(C)O[Ti](OC(C)C)(OC(C)C)OC(C)C
Agent: [Al+3]
Agent: [Cl-]
Product: C[C@H](O)COc1ccc(Oc2ccccc2)cc1
Yield: 77 %

Procedure:
In Example 2, the amount of (R,R)-(−)-N,N′-bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexanediamino cobalt (III) 4-phenoxyphenolate used was changed to 41 mg, and 15 mg of tetraisopropoxy titanium was used in place of anhydrous aluminum chloride, and the color of the catalyst solution changed from brown to slightly greenish brown by the addition of tetraisopropoxy titanium. Then 4-phenoxyphenol and propylene oxide were added to the slightly greenish brown catalyst solution to achieve the reaction in the same manner as described in Example 2. Thus (S)-(+)-1-(4-phenoxyphenoxy)-2-propanol was obtained in 77% yield and the optical purity was 94% e.e.
Reaction SMILES: [C:1]([C:5]1[CH:30]=[CH:29][C:8]([C:9]([NH:11][C:12](=[O:28])[NH:13][C:14]2[CH:19]=[CH:18][C:17]([NH:20][C:21](=[O:27])[CH2:22][CH2:23][CH2:24][CH2:25]Br)=[CH:16][CH:15]=2)=[O:10])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[NH:31]([CH3:33])[CH3:32].O.[ClH:35]>C(Cl)Cl.CC(C)=O.C(OCC)C>[ClH:35].[C:1]([C:5]1[CH:30]=[CH:29][C:8]([C:9]([NH:11][C:12](=[O:28])[NH:13][C:14]2[CH:19]=[CH:18][C:17]([NH:20][C:21](=[O:27])[CH2:22][CH2:23][CH2:24][CH2:25][N:31]([CH3:33])[CH3:32])=[CH:16][CH:15]=2)=[O:10])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)c1ccc(C(=O)NC(=O)Nc2ccc(NC(=O)CCCCBr)cc2)cc1
Reactant: CNC
Agent: Cl
Solvent: ClCCl
Solvent: CC(C)=O
Solvent: O
Product: CN(C)CCCCC(=O)Nc1ccc(NC(=O)NC(=O)c2ccc(C(C)(C)C)cc2)cc1
Yield: 36 %

Procedure:
Bromo-compound 29 (123 mg, 0.27 mmol) was stirred in CH2Cl2 (10 mL), 40% aqueous HNMe2 (3 mL) and H2O (7.5 mL) at rt for 20 h. The reaction mixture was diluted with CH2Cl2 (20 mL) and washed with H2O (1×10 mL), 10% aqueous NaOH (1×10 mL), and saturated brine (1×10 mL). The organic phase was dried over MgSO4 and concentrated in vacuo to give a cream solid which was dissolved in acetone and treated with 2 M hydrochloric acid in diethyl ether. A white precipitate was obtained and isolated by filtration to give 24 (44 mg, 36%) as a cream powder. 1H NMR (DMSO-d6, 400 MHz) δ 1.31 (s, 9H, (CH3)3), 1.64 (m, 4H, CH2)2), 2.36 (t, 2H, J=6.7 Hz, COCH2), 2.75 (s, 6H, NH(CH3)2), 3.05 (m, 2H, CH2Br), 7.53 (m, 6H, ArH), 7.98 (d, 2H, J=8.6 Hz, ArH), 9.63 (s(br), 1H, NH), 9.98 (s, 1H, NH), 10.82 (s, 1H, NH), 10.93 (s, 1H, NH).
Reaction SMILES: [CH3:1][O:2][CH2:3][C:4](=[O:10])[CH2:5][C:6]([O:8][CH3:9])=[O:7].[H-].[Na+].Br[CH2:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]2[C:22]([C:27]#[N:28])=[CH:23][CH:24]=[CH:25][CH:26]=2)=[CH:17][CH:16]=1>O1CCCC1>[C:27]([C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][C:21]=1[C:18]1[CH:17]=[CH:16][C:15]([CH2:14][CH:5]([C:4](=[O:10])[CH2:3][O:2][CH3:1])[C:6]([O:8][CH3:9])=[O:7])=[CH:20][CH:19]=1)#[N:28]
Reactant: N#Cc1ccccc1-c1ccc(CBr)cc1
Reactant: COCC(=O)CC(=O)OC
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: COCC(=O)C(Cc1ccc(-c2ccccc2C#N)cc1)C(=O)OC
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 97.6 %

Procedure:
A solution of methyl 4-methoxy-3-oxobutyrate (10.7 g) in tetrahydrofuran (150 mL) was added to a mixture of sodium hydride (1.91 g) and tetrahydrofuran (150 mL) at room temperature, and the mixture was stirred at room temperature for 30 min. 4′-(Bromomethyl)biphenyl-2-carbonitrile (10 g) was added to the reaction mixture, and the reaction mixture was stirred at room temperature for 3 days. The reaction mixture was concentrated. To the residue were added 5% aqueous potassium hydrogen sulfate solution and then ethyl acetate, and the mixture was extracted. The ethyl acetate layer was washed with saturated brine and concentrated. The residue was purified by silica gel column chromatography to give the title compound as a colorless oil (12.1 g, 98%).
Reaction SMILES: [C:1]([NH:9][C@@H:10]([CH:32]([CH3:34])[CH3:33])[C:11]([N:13]([CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[CH2:14][C:15]([NH:17][C@H:18]([CH:23]=[O:24])[CH2:19][C:20]([OH:22])=[O:21])=[O:16])=[O:12])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(OC(=O)C[N:40](C(=O)[C@@H](NC(=O)C1C=CC=CC=1)C(C)C)CC1C=CC=C(NC(OC(C)(C)C)=O)C=1)C>>[C:1]([NH:9][C@@H:10]([CH:32]([CH3:34])[CH3:33])[C:11]([N:13]([CH2:25][C:26]1[CH:27]=[CH:28][CH:29]=[C:30]([NH2:40])[CH:31]=1)[CH2:14][C:15]([NH:17][C@H:18]([CH:23]=[O:24])[CH2:19][C:20]([OH:22])=[O:21])=[O:16])=[O:12])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CCOC(=O)CN(Cc1cccc(NC(=O)OC(C)(C)C)c1)C(=O)[C@@H](NC(=O)c1ccccc1)C(C)C
Reactant: CC(C)[C@H](NC(=O)c1ccccc1)C(=O)N(CC(=O)N[C@H](C=O)CC(=O)O)Cc1ccccc1
Product: CC(C)[C@H](NC(=O)c1ccccc1)C(=O)N(CC(=O)N[C@H](C=O)CC(=O)O)Cc1cccc(N)c1

Procedure:
Compound 737 was prepared by a method similar to the method used to prepare compound 706, except compound 703 was replaced with compound 736. ##STR116##
Reaction SMILES: [C:1]([CH2:3][C:4]1[CH:5]=[C:6]([CH:11]=[CH:12][CH:13]=1)[C:7]([O:9][CH3:10])=[O:8])#[N:2].[H-].[Na+].Br[CH2:17][CH2:18]Br>CS(C)=O>[C:1]([C:3]1([C:4]2[CH:5]=[C:6]([CH:11]=[CH:12][CH:13]=2)[C:7]([O:9][CH3:10])=[O:8])[CH2:18][CH2:17]1)#[N:2]
Reactant: BrCCBr
Reactant: COC(=O)c1cccc(CC#N)c1
Agent: [H-]
Agent: [Na+]
Solvent: CS(C)=O
Product: COC(=O)c1cccc(C2(C#N)CC2)c1
Yield: 75.1 %

Procedure:
Using methyl 3-(cyanomethyl)benzoate (1.5 g, 8.6 mmol), sodium hydride (60% in oil, 1.0 g, 26 mmol), 1,2-dibromoethane (2.4 g, 13 mmol) and dimethyl sulfoxide (30 mL) as starting materials and in the same manner as in Reference Example 31, the title compound (1.3 g, 76%) was obtained as a colorless oil.
Reaction SMILES: [CH3:1][CH:2]1[C:7](=O)[CH2:6][CH2:5][O:4][CH2:3]1.[CH2:9]([NH2:16])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl>[CH2:9]([NH:16][C@H:7]1[CH2:6][CH2:5][O:4][CH2:3][C@H:2]1[CH3:1])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1
Reactant: CC1COCCC1=O
Reactant: NCc1ccccc1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: ClCCl
Product: C[C@@H]1COCC[C@@H]1NCc1ccccc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 100.1 %

Procedure:
Racemic 3-methyl-tetrahydro-pyran-4-one (1 g, 8.761 mmol) was dissolved in DCM. Benzylamine (1.5 mL, 13.75 mmol) and sodium triacetoxyborohydride (95%, 3.3 g, 14.89 mmol) were added and the resulting suspension was stirred at RT overnight. The reaction mixture was washed with saturated aqueous NaHCO3. The aqueous layer was extracted with DCM. The combined organic layers were washed with brine, dried (Na2SO4), filtered and evaporated. The remaining yellow liquid was purified by SiO2 chromatography (120 g SiO2, DCM/(DCM:MeOH:NH4OH 60:10:1) 92% DCM) to give 1.8 g of racemic cis benzyl-(3-methyl-tetrahydro-pyran-4-yl)-amine as a light yellow oil (>95% yield).
Reaction SMILES: [NH2:1][CH:2]1[CH2:8][S:7][CH:6]([C:9]2[CH:18]=[CH:17][C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[CH:10]=2)[CH2:5][N:4]([CH2:19][C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[C:3]1=[O:27].Br[CH:29]([CH2:35][CH2:36][C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)[C:30]([O:32][CH2:33][CH3:34])=[O:31].C(OCC)(=O)C>C(Cl)Cl>[CH2:33]([O:32][C:30]([CH:29]([NH:1][CH:2]1[CH2:8][S:7][CH:6]([C:9]2[CH:18]=[CH:17][C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[CH:10]=2)[CH2:5][N:4]([CH2:19][C:20]([O:22][C:23]([CH3:24])([CH3:26])[CH3:25])=[O:21])[C:3]1=[O:27])[CH2:35][CH2:36][C:37]1[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=1)=[O:31])[CH3:34]
Reactant: CCOC(=O)C(Br)CCc1ccccc1
Reactant: CC(C)(C)OC(=O)CN1CC(c2ccc3ccccc3c2)SCC(N)C1=O
Solvent: ClCCl
Solvent: CCOC(C)=O
Product: CCOC(=O)C(CCc1ccccc1)NC1CSC(c2ccc3ccccc3c2)CN(CC(=O)OC(C)(C)C)C1=O

Procedure:
0.85 g of t-butyl α-[6-amino-2-(2-naphthyl)-5-oxoperhydro-1,4-thiazepin-4-yl]acetate [prepared as described in step (g) above] was subjected to N-alkylation with 1.08 g of ethyl 2-bromo-4-phenylbutyrate in the same manner as described in Example 36(h). The reaction product was subjected to silica gel column chromatography, using a 1:30 by volume mixture of ethyl acetate and methylene chloride, to separate it into two isomers, A and B (ascribed to the asymmetric carbon atom to which the phenethyl group is attached).
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].[CH2:7]([CH:9]([CH2:12][CH2:13][CH2:14][CH3:15])[CH2:10][NH2:11])[CH3:8].[CH:16]1[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[CH:19]=[CH:18][C:17]=1[O:26][CH2:27][CH2:28]Cl>CS(C)=O.O>[CH2:7]([CH:9]([CH2:12][CH2:13][CH2:14][CH3:15])[CH2:10][NH:11][CH2:28][CH2:27][O:26][C:17]1[CH:18]=[CH:19][C:20]2[C:25](=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH:16]=1)[CH3:8]
Reactant: ClCCOc1ccc2ccccc2c1
Reactant: CCCCC(CC)CN
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CS(C)=O
Product: CCCCC(CC)CNCCOc1ccc2ccccc2c1
Temperature: 140 °C

Procedure:
A mixture of anhydrous potassium carbonate (10 gm, in excess) and 2-ethyl n-hexylamine (0.37 ml, 0.003 mole) was taken in dry DMSO(40 ml). Now 2-(2-naphthyloxy)-1-chloroethane (0.5 gm, 0.002 mole) was added in it. Reaction mixture was refluxed at 140° C. for 7 hrs and the reaction was completed as checked by TLC. Reaction mixture was poured in distilled water (60 ml) and extracted with ethyl acetate thrice. The organic layer was separated and concentrated to get oily compound which was later crystallized by benzene hexane to get N-(2-ethyl-n-hexyl)-(2-(naphthalen-2-yloxy)ethyl]amine, solid, m.p. 92° C., (yield 0.62 gm, 83.6%).
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[C:6]2[N:7]([CH:11]=[CH:12][N:13]=2)[CH:8]=[CH:9][CH:10]=1)=[O:4].[I:14]N1C(=O)CCC1=O>C(#N)C>[CH3:1][O:2][C:3]([C:5]1[C:6]2[N:7]([C:11]([I:14])=[CH:12][N:13]=2)[CH:8]=[CH:9][CH:10]=1)=[O:4]
Reactant: COC(=O)c1cccn2ccnc12
Reactant: O=C1CCC(=O)N1I
Solvent: CC#N
Product: COC(=O)c1cccn2c(I)cnc12
Temperature: 25 °C
Reaction time: 2 h

Procedure:
A mixture of imidazo[1,2-a]pyridine-8-carboxylic acid methyl ester (3.24 g, 18.3 mmol) and N-iodosuccinimide (NIS) (4.11 g, 18.3 mmol) in acetonitrile (50 mL) is stirred at room temperature. After 2 hours, the reaction mixture is quenched with saturated aqueous Na2S2O3 and extracted with EtOAc (3×100 mL). The combined organic layers are washed with water, brine, dried over Na2SO4 and concentrated. The crude material is purified by silica gel chromatography eluting with 80% EtOAc in hexanes to afford 3-iodo-imidazo[1,2-a]pyridine-8-carboxylic acid methyl ester. Mp: 99-110° C.
Reaction SMILES: [NH2:1][CH2:2][C:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6](=[O:13])[N:5]([NH:14][C:15](=[O:24])[CH2:16][C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=2)[N:4]=1.[C:25](Cl)(=[O:32])[O:26][CH:27]1[CH2:31][CH2:30][CH2:29][CH2:28]1>>[CH:27]1([O:26][C:25](=[O:32])[NH:1][CH2:2][C:3]2[C:12]3[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=3)[C:6](=[O:13])[N:5]([NH:14][C:15](=[O:24])[CH2:16][C:17]3[CH:18]=[CH:19][C:20]([Cl:23])=[CH:21][CH:22]=3)[N:4]=2)[CH2:31][CH2:30][CH2:29][CH2:28]1
Reactant: O=C(Cl)OC1CCCC1
Reactant: NCc1nn(NC(=O)Cc2ccc(Cl)cc2)c(=O)c2ccccc12
Product: O=C(Cc1ccc(Cl)cc1)Nn1nc(CNC(=O)OC2CCCC2)c2ccccc2c1=O

Procedure:
The product of Example 42 and cyclopentyl carbonochloridate were treated using a method similar to that described in Example 128 to give the title compound. 1H NMR (300 MHz, DMSO-d6) δ ppm 11.60-11.62 (bs, 1H), 8.32 (d, J=7.8 Hz, 1H), 8.10 (d, J=8.0 Hz, 1H), 7.88-8.03 (m, 2H), 7.58-7.64 (m, 1H), 7.23-7.45 (m, 4H), 4.95-5.01 (bs, 1H), 4.47-4.50 (m, 2H), 3.67-3.68 (bs, 2H), 1.76-1.81 (m, 2H), 1.50-1.69 (m, 6H); MS (ESI+) M/Z 455 (M+H)+.