Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [O:1]([CH2:8][C:9]([O:11]CC)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].[Na+].C(O)(=O)C>C1COCC1.O>[O:1]([CH2:8][C:9]([OH:11])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CCOC(=O)COc1ccccc1
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CC(=O)O
Solvent: O
Product: O=C(O)COc1ccccc1
Temperature: 25 °C
Reaction time: 24 h
Yield: 94.4 %

Procedure:
Compound 34 (2 g, 0.011 mol) was dissolved in 100 mL of THF, and 1 M NaOH (110 mL, 0.11 mol) was added. The reaction mixture was stirred at RT for 24 h. The solution was then acidified by the addition of 40 mL of acetic acid. The reaction mixture was diluted with 150 mL of H2O and the product was extracted with ethyl acetate. The organic extracts were dried over magnesium sulfate and concentrated. The crude product was washed several times with hexane:ethylacetate (9:1) to give a pale white solid (1.58 g, 94%). 1H NMR (300 MHz, CD2Cl2) δ 4.69 (s, 2H), 6.92 (d, J=8.2 Hz, 2H), 7.03 (t, J=7.0 Hz, 1H), 7.32 (t, J=7.6 Hz, 2H).
Reaction SMILES: C1N=C(N)C2N=CN([C@@H]3O[C@H](COP(OP(OC[C@H]4O[C@@H](N5[CH:36]=[C:35]([C:37](N)=O)[CH2:34][CH:33]=[CH:32]5)[C@H](O)[C@@H]4O)(O)=O)(O)=O)[C@@H](O)[C@H]3O)C=2N=1.[CH:45]1([C:48](C2C=CC=CC=2)=[O:49])CC1.P([O-])([O-])([O-])=O.[OH-].[Na+]>C(OCC)C.CCCCCC.CC(O)C>[CH3:37][C:35]([CH3:36])=[CH:34][CH2:33][CH2:32][C@H:48]([OH:49])[CH3:45]
Reactant: NC(=O)C1=CN([C@@H]2O[C@H](COP(=O)(O)OP(=O)(O)OC[C@H]3O[C@@H](n4cnc5c(N)ncnc54)[C@H](O)[C@@H]3O)[C@@H](O)[C@H]2O)C=CC1
Reactant: O=C(c1ccccc1)C1CC1
Agent: O=P([O-])([O-])[O-]
Agent: [Na+]
Agent: [OH-]
Solvent: CC(C)O
Solvent: CCCCCC
Solvent: CCOCC
Product: CC(C)=CCC[C@@H](C)O
Temperature: 25 °C

Procedure:
A reaction mixture was formed by admixing (i) 50 mg NAD, (ii) 4 ml of 2-propanol and (iii) 5 mmoles of 6-methyl-5-hepten-2-one, Compound 10, in a liquid medium containing 1 gm of lyophilized PED alcohol dehydrogenase preparation, 75 ml of 50 mM phosphate buffer, pH 7.1, and 25 ml of hexane. The pH value of the reaction was maintained constant by addition of 1N NaOH. The reaction mixture was maintained at room temperature until product formation stopped. When product formation stopped, (R)-6-methyl-5-hepten-2-ol, Compound 10a, was isolated by removal of the hexane layer and extraction of the aqueous layer with ethyl ether (3×75 ml).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([OH:29])[CH2:9][CH2:10][N:11]2[CH2:16][CH2:15][CH:14]([C:17]3[CH:18]=[C:19]([NH:23][C:24](=[O:28])[CH:25]([CH3:27])[CH3:26])[CH:20]=[CH:21][CH:22]=3)[CH2:13][CH2:12]2)=[CH:4][CH:3]=1.[F:30][C:31]1[CH:32]=[C:33](O)[CH:34]=[CH:35][C:36]=1[F:37]>>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]([O:29][C:34]2[CH:33]=[CH:32][C:31]([F:30])=[C:36]([F:37])[CH:35]=2)[CH2:9][CH2:10][N:11]2[CH2:16][CH2:15][CH:14]([C:17]3[CH:18]=[C:19]([NH:23][C:24](=[O:28])[CH:25]([CH3:26])[CH3:27])[CH:20]=[CH:21][CH:22]=3)[CH2:13][CH2:12]2)=[CH:6][CH:7]=1
Reactant: Oc1ccc(F)c(F)c1
Reactant: CC(C)C(=O)Nc1cccc(C2CCN(CCC(O)c3ccc(Cl)cc3)CC2)c1
Product: CC(C)C(=O)Nc1cccc(C2CCN(CCC(Oc3ccc(F)c(F)c3)c3ccc(Cl)cc3)CC2)c1

Procedure:
Prepared by Procedure A and Scheme AN using N-(3-{1-[3-(4-chlorophenyl)-3-hydroxypropyl]-4-piperidinyl}phenyl)-2-methylpropanamide and 3,4-difluorophenol: ESMS m/e: 526.8 (M+H)+.
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][OH:14].[CH3:15][NH:16][CH3:17]>O1CCCC1.C(OCC)(=O)C>[CH3:15][N:16]([CH3:17])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][OH:14]
Reactant: CNC
Reactant: OCCCCCCCCCCCCBr
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: CN(C)CCCCCCCCCCCCO
Temperature: 25 °C
Reaction time: 72 h

Procedure:
A solution of 12-bromo-1-dodecanol (1 g, 3.8 mmoles) in anhydrous tetrahydrofuran (10 mL) was treated with a 2.0 M solution of dimethylamine in tetrahydrofuran (10 mL). The reaction was stirred at room temperature for 3 days. TLC analysis on silica using 25% ethyl acetate, 75% hexanes as eluent showed the formation of a polar product with little starting material. The reaction was diluted with ethyl acetate (75 mL) and washed twice with aqueous sodium bicarbonate and water. The ethyl acetate solution was then dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. Yield=1.2 g (wax). TLC analysis on silica (25% methanol, 75% ethyl acetate) showed a streaking product with Rf ˜0.1. This product 4a, was used without purification.
Reaction SMILES: ON=C(C1C=CC=CC=1)C#N.CN(C)C1C=CC=CC=1.ClC(OC(Cl)(Cl)Cl)=O.[CH:29]1([CH:32]([OH:34])[CH3:33])[CH2:31][CH2:30]1.Cl[C:36]([O:38][N:39]=[C:40]([C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1)[C:41]#[N:42])=[O:37]>C1C=CC=CC=1.O1CCOCC1.N1C=CC=CC=1>[CH:29]1([CH:32]([O:34][C:36]([O:38][N:39]=[C:40]([C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)[C:41]#[N:42])=[O:37])[CH3:33])[CH2:31][CH2:30]1
Reactant: N#CC(=NOC(=O)Cl)c1ccccc1
Reactant: CC(O)C1CC1
Agent: N#CC(=NO)c1ccccc1
Agent: O=C(Cl)OC(Cl)(Cl)Cl
Solvent: c1ccncc1
Solvent: CN(C)c1ccccc1
Solvent: c1ccccc1
Product: CC(OC(=O)ON=C(C#N)c1ccccc1)C1CC1
Reaction time: 3 h

Procedure:
A solution of 2-hydroxyimino-2-phenylacetonitrile (2.2 g.) and dimethylaniline (1.80 g.) in a mixture of benzene (25 ml.) and dioxane (3 ml.) was added dropwise to a solution of trichloromethyl chloroformate (phosgene dimer) (1.5 g.) in benzene (20 ml.) under ice-cooling. The mixture was stirred for 3 hours at the same temperature and allowed A solution of 1-cyclopropylethanol (1.4 g.) and pyridine (1.2 ml.) in benzene (10 ml.) was added dropwise, under ice-cooling, to the resultant mixture containing 2-chlorocarbonyloxyimino-2-phenylacetonitrile. The mixture was stirred for 2 hours at the same temperature, for 4 hours at room temperature and allowed to stand overnight. The reaction mixture was then washed with 1N hydrochloric acid, water, a sodium bicarbonate aqueous solution and water, and dried over magnesium sulfate. The solvent was distilled off and a small amount of methanol was added to the oily residue. The mixture was allowed to stand in a refrigerator and the precipitated crystals were collected by filtration and recrystallized from methanol to give 2-(1-cyclopropylethoxycarbonyloxyimino)-2-phenylacetonitrile (0.7 g.), mp 65° to 67° C.
Reaction SMILES: [ClH:1].C(OC([NH:9][CH2:10][C:11]([NH:13][C@H:14]1[CH2:18][N:17](C(OC(C)(C)C)=O)[C@H:16]([C:26]([N:28]2[CH2:33][CH2:32][CH:31]([O:34][C:35]3[CH:40]=[CH:39][C:38]([O:41][CH2:42][C:43]4[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=4)=[CH:37][CH:36]=3)[CH2:30][CH2:29]2)=[O:27])[CH2:15]1)=[O:12])=O)(C)(C)C>O1CCOCC1>[ClH:1].[ClH:1].[NH2:9][CH2:10][C:11]([NH:13][C@H:14]1[CH2:18][NH:17][C@H:16]([C:26]([N:28]2[CH2:33][CH2:32][CH:31]([O:34][C:35]3[CH:36]=[CH:37][C:38]([O:41][CH2:42][C:43]4[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=4)=[CH:39][CH:40]=3)[CH2:30][CH2:29]2)=[O:27])[CH2:15]1)=[O:12]
Reactant: CC(C)(C)OC(=O)NCC(=O)N[C@@H]1C[C@@H](C(=O)N2CCC(Oc3ccc(OCc4ccccc4)cc3)CC2)N(C(=O)OC(C)(C)C)C1
Agent: Cl
Solvent: C1COCCO1
Product: NCC(=O)N[C@H]1CN[C@H](C(=O)N2CCC(Oc3ccc(OCc4ccccc4)cc3)CC2)C1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
A solution of 4 N hydrochloric acid in 1,4-dioxane (9 mL) was added to a solution of 1-[trans-4-(N-tert-butoxycarbonylglycylamino)-N-tert-butoxycarbonyl-L-Prolyl]-4-(4-benzyloxyphenoxy)piperidine (D, 330 mg) in 1,4-dioxane (9 mL) at room temperature. After stirring at room temperature for 30 min, the reaction mixture was concentrated in vacuo. The residue was washed with ether to give the titled compound (186 mg) as a white powder: 1H NMR (400 MHz, D2O) δ 1.58 (br s, 2H), 1.83 (br s, 2H), 2.25 (m, 1H), 2.43 (m, 1H), 3.20-3.40 (m, 3H), 3.50-3.70 (m, 3H), 3.70 (s, 2H), 4.41 (m, 1H), 4.85 (t, J=8.30 Hz, 1H), 4.93 (s, 2H), 6.85 (s, 4H), and 7.24-7.31 (m, 5H); mass spectrum (E+) m/e 452; IR (KBr) 3438, 3059, 1689, 1651, 1549, 1508, 1228, 1024, 825, 741, and 698 cm−1; Anal. Calcd for C25H32N4O4.2HCl.0.5H2O: C, 56.18; H, 6.60; N, 10.48; Cl, 13.27. Found: C, 56.56; H, 6.61; N, 10.05; Cl, 12.72.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:15]=[CH:14][C:11]([CH:12]=[O:13])=[CH:10][CH:9]=1.[BH4-].[Na+]>C(O)C>[Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:9]=[CH:10][C:11]([CH2:12][OH:13])=[CH:14][CH:15]=1
Reactant: O=Cc1ccc(-c2ccccc2Br)cc1
Agent: [BH4-]
Agent: [Na+]
Solvent: CCO
Product: OCc1ccc(-c2ccccc2Br)cc1
Reaction time: 1 h

Procedure:
To a solution of 4-(2'-bromophenyl)benzaldehyde 1.55 g, 7.95 mmol) in ethanol (15 mL) at 0° C. was added sodium borohydride (2.22 g, 58.7 mmol) and the reation stirred for 1 hour. The reaction was quenched with saturated aq. NH4Cl and extracted into diethyl ether. The organic extracts were washed with brine, dried, (Na2SO4) and evaporated in vacuo. The residue was purified by chromatography (Silica gel, 25% EtOAc in hexanes) to afford the title compound as a colourless oil.
Reaction SMILES: Cl.[NH2:2][C@H:3]([C:5]([OH:7])=[O:6])[CH3:4]>>[NH2:2][C@H:3]([C:5]([OH:7])=[O:6])[CH2:4][CH2:3][C:5]([OH:7])=[O:6]
Reactant: C[C@H](N)C(=O)O
Agent: Cl
Product: N[C@@H](CCC(=O)O)C(=O)O

Procedure:
Acid hydrolysis: Acid hydrolysis with 6N-HCl yields alanine, and acid hydrolysis with 6N-HCl subsequent to oxidation with HIO4 yields glutamic acid.
Reaction SMILES: [N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4]([N:11]2[CH2:16][CH2:15][NH:14][CH2:13][C:12]2=[O:17])=[CH:3][CH:2]=1.C(N(CC)CC)C.[CH3:25][CH:26]([CH3:32])/[CH:27]=[CH:28]/[C:29](Cl)=[O:30]>ClCCl>[CH3:25][CH:26]([CH3:32])/[CH:27]=[CH:28]/[C:29]([N:14]1[CH2:15][CH2:16][N:11]([C:4]2[C:5]3[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=3)[N:1]=[CH:2][CH:3]=2)[C:12](=[O:17])[CH2:13]1)=[O:30]
Reactant: O=C1CNCCN1c1ccnc2ccccc12
Reactant: CC(C)/C=C/C(=O)Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(C)/C=C/C(=O)N1CCN(c2ccnc3ccccc23)C(=O)C1

Procedure:
1-(4-Quinolyl)piperazin-2-one (23 mg, 0.1 mmol) was dissolved in dichloromethane (1 ml), triethylamine was added (21 μl, 0.15 mmol) followed by a solution of (E)-4-methylpent-2-enoyl chloride in 0.5 ml dichloromethane. The mixture was shaken briefly, washed with 5% sodium bicarbonate solution (2×), water and evaporated to dryness. The raw product was purified by preparative HPLC (gradient of water containing 0.1% ammonia and acetonitrile). 14.4 mg of a solid residue were obtained (0.044 mmol, 44%).
Reaction SMILES: [NH2:1][CH2:2][CH2:3][CH2:4][CH2:5][N:6]1[C:18]2[C:17]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[N:11]=[C:10]([NH2:19])[C:9]=2[N:8]=[CH:7]1.[C:20](Cl)(=[O:27])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>N1C=CC=CC=1>[NH2:19][C:10]1[C:9]2[N:8]=[CH:7][N:6]([CH2:5][CH2:4][CH2:3][CH2:2][NH:1][C:20](=[O:27])[C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[C:18]=2[C:17]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[N:11]=1
Reactant: NCCCCn1cnc2c(N)nc3ccccc3c21
Reactant: O=C(Cl)c1ccccc1
Solvent: c1ccncc1
Product: Nc1nc2ccccc2c2c1ncn2CCCCNC(=O)c1ccccc1
Temperature: 60 °C
Reaction time: 1 h

Procedure:
A suspension of 1-(4-aminobutyl)-1H-imidazo[4,5-c]quinolin-4-amine (2.0 g, 7.8 mmol) in pyridine (1 L) was warmed to 60° C. to dissolve the starting material. The solution was cooled to about 30° C. and then benzoyl chloride (1.1 g, 7.8 mmol) diluted with pyridine (100 mL) was slowly added. After 1 hour analysis by high performance liquid chromatography (HPLC) indicated that some starting material remained. Additional benzoyl chloride (0.3 g) was added and the reaction was warmed to 50° C. overnight. The reaction mixture was concentrated under vacuum. The resulting residue was combined with chloroform (200 mL) and 1% sodium carbonate (200 mL). The organic layer was separated and then concentrated under vacuum. The resulting residue was combined with propyl acetate (30 mL) and heated on a steam bath to dissolve the residue. The solution was allowed to cool. The resulting precipitate was isolated by filtration to provide N1-[4-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]benzamide as a solid, m.p. 210-212° C. Analysis: Calculated for C21H21N5O: % C, 70.18; % H, 5.89; % N, 19.48. Found: % C, 69.49; % H, 5.97; % N, 19.64. 1H NMR (500 MHz, DMSO-d6) δ 8.48 (t, J=6.0 Hz, 1H), 8.22 (s, 1H), 8.04 (d, J=8.0 Hz, 1H), 7.78 (d, J=8.0 Hz, 2H), 7.61 (d, J=8.0 Hz, 1H),7.50 (t, J=8.0 Hz, 1H), 7.43 (m, 3H), 7.21 (t, J=8.0 Hz, 1H), 6.62 (broad s, 2H), 4.64 (t, J=7.0 Hz, 2H), 3.30 (q, J=6.0 Hz, 2H), 1.92 (quintet, J=7.0 Hz, 2H), 1.58 (quintet, J=7.0 Hz, 2H); MS (EI) m/e 359.1746 (359.1746 calcd for C21H21N5O).
Reaction SMILES: [C:1]([C:5]1[CH:6]=[C:7]([CH:12]=[C:13]([O:15][CH2:16][CH2:17][CH2:18][O:19][CH:20]2[CH2:25][CH2:24][CH2:23][CH2:22][O:21]2)[CH:14]=1)[C:8]([O:10]C)=[O:9])([CH3:4])([CH3:3])[CH3:2].[OH-].[Li+].C(Cl)Cl>CO.C1COCC1>[C:1]([C:5]1[CH:6]=[C:7]([CH:12]=[C:13]([O:15][CH2:16][CH2:17][CH2:18][O:19][CH:20]2[CH2:25][CH2:24][CH2:23][CH2:22][O:21]2)[CH:14]=1)[C:8]([OH:10])=[O:9])([CH3:4])([CH3:2])[CH3:3]
Reactant: COC(=O)c1cc(OCCCOC2CCCCO2)cc(C(C)(C)C)c1
Agent: [Li+]
Agent: [OH-]
Solvent: ClCCl
Solvent: CO
Solvent: C1CCOC1
Product: CC(C)(C)c1cc(OCCCOC2CCCCO2)cc(C(=O)O)c1
Temperature: 40 °C
Reaction time: 2 h
Yield: 95.1 %

Procedure:
Methyl 3-tert-butyl-5-[3-(tetrahydropyran-2-yloxy)propoxy]benzoate (O5.059; 5.37 g) was dissolved in methanol (80 ml) and THF (160 ml), and lithiumhydroxide solution (61.28 ml, 1 M in water) was added. After stirring at 40° C. for 2 h, the mixture was dried, and the residue was taken up with water and freeze-dried. The product obtained was stirred with DCM, filtered and dried. 4.9 g of product were obtained.
Reaction SMILES: [Cl-:1].[CH3:2][N+:3]([CH3:15])([CH2:7][C:8]1([CH3:14])[CH2:12][O:11][C:10](=[O:13])[NH:9]1)[CH2:4][CH2:5][CH3:6].C(O[Cl:21])(C)(C)C>CO>[Cl-:21].[Cl:1][N:9]1[C:8]([CH2:7][N+:3]([CH3:2])([CH3:15])[CH2:4][CH2:5][CH3:6])([CH3:14])[CH2:12][O:11][C:10]1=[O:13]
Reactant: CCC[N+](C)(C)CC1(C)COC(=O)N1
Reactant: CC(C)(C)OCl
Agent: [Cl-]
Solvent: CO
Product: CCC[N+](C)(C)CC1(C)COC(=O)N1Cl
Yield: 15 %

Procedure:
To a solution of N,N-dimethyl-N-((4-methyl-2-oxooxazolidin-4-yl)methyl)propan-1-aminium chloride (6.51 mmol) in MeOH (5 ml) was added, dropwise, tert-butylhypochlorite (˜2.5 ml) until the reaction mixture was clear with white precipitate. The solution was filtered through a 0.45 μm nylon filter, then evaporated and purified on preparative HPLC (H2O/MeOH) to afford the title compound as a white foam (248.1 mg, 0.9648 mmol, 15% over two steps). 1H NMR (D2O, 400 MHz) δ 0.99 (t, J=7.2 Hz, 3H), 1.64 (s, 3H), 1.8-2.0 (m, 2H), 3.24 (s, 3H), 3.26 (s, 3H), 3.40-3.45 (m, 2H), 3.75 (d, J=15.2 Hz, 1H), 3.82 (d, J=15.2 Hz, 1H), 4.62 (d, J=9.6 Hz, 1H), 4.90 (d, J=9.6 Hz, 1H). ESI/APCI expected for C10H20ClN2O2+: 235.12. Found: 235.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C@@H:8]([OH:41])[CH2:9][N:10]([C@@H:18]([CH2:21][C:22]2[CH:27]=[CH:26][C:25]([NH:28][C:29]([C:31]3[CH:32]=[C:33]4[C:37](=[CH:38][CH:39]=3)[N:36]([CH3:40])[CH:35]=[CH:34]4)=[O:30])=[CH:24][CH:23]=2)[CH2:19][OH:20])C(=O)OC(C)(C)C)[CH:5]=[CH:6][CH:7]=1>Cl.C(O)C>[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:8]([OH:41])[CH2:9][NH:10][C@H:18]([CH2:19][OH:20])[CH2:21][C:22]2[CH:23]=[CH:24][C:25]([NH:28][C:29]([C:31]3[CH:32]=[C:33]4[C:37](=[CH:38][CH:39]=3)[N:36]([CH3:40])[CH:35]=[CH:34]4)=[O:30])=[CH:26][CH:27]=2)[CH:5]=[CH:6][CH:7]=1
Reactant: Cn1ccc2cc(C(=O)Nc3ccc(C[C@@H](CO)N(C[C@H](O)c4cccc(Cl)c4)C(=O)OC(C)(C)C)cc3)ccc21
Agent: Cl
Solvent: CCO
Product: Cn1ccc2cc(C(=O)Nc3ccc(C[C@@H](CO)NC[C@H](O)c4cccc(Cl)c4)cc3)ccc21
Temperature: 25 °C
Reaction time: 5 h
Yield: 41 %

Procedure:
tert-Butyl N-[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]-N-[(1S)-2-hydroxy-1-(4-[[(1-methyl-1H-indol-5-yl)carbonyl]amino]benzyl]ethyl]carbamate (101 mg) was dissolved in 4N hydrogen chloride in ethanol (1.0 ml) and the solution was stirred at room temperature for 5 hours. The solvent was removed by evaporation and the residual solid was dissolved in methanol. To the solution was added 1N sodium hydroxide solution (175 μl) and the solvent was removed by evaporation. The residue was chromatographed on silica gel (eluent: chloroform/methanol=9/1) to give N-[4-[(2S)-2-[[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]-3-hydroxypropyl]phenyl]-1-methyl-1H-indole-5-carboxamide (34.2 mg) as a pale yellow solid.
Reaction SMILES: [CH2:1]([N:8]([CH2:13][C@H:14]([C:16]1[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=1)[OH:15])[C:9](=[O:12])[CH2:10]Cl)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(O)(C)(C)C.CC(C)([O-])C.[K+].[Cl-].[NH4+]>O>[CH2:1]([N:8]1[CH2:13][C@H:14]([C:16]2[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=2)[O:15][CH2:10][C:9]1=[O:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C(CCl)N(Cc1ccccc1)C[C@@H](O)c1ccc(F)cc1
Agent: CC(C)(C)[O-]
Agent: [Cl-]
Agent: [K+]
Solvent: CC(C)(C)O
Solvent: O
Product: O=C1CO[C@@H](c2ccc(F)cc2)CN1Cc1ccccc1
Temperature: 22 °C
Reaction time: 1.5 h
Yield: 97.8 %

Procedure:
Add N-benzyl-2-chloro-N-[(2S)-2-(4-fluorophenyl)-2-hydroxyethyl]acetamide (1440 g, 4.48 mol) to tert-butyl alcohol (14.5 L) and add potassium tert-butoxide (753 g, 6.73 mol) portion-wise while maintaining the mixture at 22° C. Maintain the mixture at 22° C. and stir for 1.5 hours. Add a saturated aqueous solution of ammonium chloride (1306 g) to quench the reaction. Stir for an additional 1 hour and then add H2O (2 L). Extract with EtOAc (2×10 L); combine the extracts; and concentrate the extracts under reduced pressure provide a residue. Re-dissolve the residue in EtOAc (20 L) and wash with H2O (10 L). Dry the EtOAc solution over Na2SO4 and filter. Collect the filtrate and remove the solvent under reduced pressure to provide the title compound as a colorless oil (1250 g, 98%). MS (m/z): 286 (M+1).
Reaction SMILES: [C:1]1(=[O:11])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][CH2:2]1.C[Si]([C:16]#[N:17])(C)C.[Cl-].[Cl-].[Cl-].[Al+3].[H-].[Al+3].[Li+].[H-].[H-].[H-]>>[NH2:17][CH2:16][C:1]1([OH:11])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][CH2:2]1
Reactant: C[Si](C)(C)C#N
Reactant: O=C1CCCc2ccccc21
Agent: [Al+3]
Agent: [Cl-]
Agent: [H-]
Product: NCC1(O)CCCc2ccccc21

Procedure:
As set forth in the foregoing reaction scheme, the 1-aminoalkyl-3,4-dihydronaphthalene compounds of the invention wherein n is 1 are obtained by reacting a 1,2,3,4-tetrahydro-1-naphthalenone with, for example, trimethylsilylcyanide in the presence of a catalytic amount of, for example, aluminum trichloride followed by reduction with lithium aluminum hydride to obtain the corresponding 1-aminomethyl-1-hydroxy-1,2,3,4-tetrahydronaphthalene. Similarly, the compounds of the invention wherein n is 2 may be obtained by reacting a 1,2,3,4-tetrahydro-1-naphthalenone with, for example, acetonitrile and n-butyl lithium, followed by reduction with lithium aluminum hydride to obtain the corresponding 1-aminoethyl-1-hydroxy-1,2,3,4-tetrahydronaphthalene. The 1-aminoalkyl-1-hydroxy-1,2,3,4-tetrahydronaphthalene intermediate is then subjected to acid dehydration to obtain the corresponding 1-aminoalkyl-3,4-dihydronaphthalene compound.
Reaction SMILES: [F:1][C:2]1[N:7]=[C:6]([NH2:8])[CH:5]=[CH:4][CH:3]=1.[Cl:9][C:10]1[CH:17]=[CH:16][CH:15]=[CH:14][C:11]=1[CH:12]=O.C([SiH](CC)CC)C.FC(F)(F)C(O)=O>C(#N)C>[Cl:9][C:10]1[CH:17]=[CH:16][CH:15]=[CH:14][C:11]=1[CH2:12][NH:8][C:6]1[CH:5]=[CH:4][CH:3]=[C:2]([F:1])[N:7]=1
Reactant: O=Cc1ccccc1Cl
Reactant: Nc1cccc(F)n1
Agent: CC[SiH](CC)CC
Solvent: O=C(O)C(F)(F)F
Solvent: CC#N
Product: Fc1cccc(NCc2ccccc2Cl)n1
Temperature: 80 °C
Reaction time: 4 h

Procedure:
To 6-fluoro-pyridin-2-ylamine (14, 2.47 g, 22.0 mmol) in 60.0 mL of acetonitrile, 2-chloro-benzaldehyde (15, 3.09 g, 22.0 mmol), triethylsilane (14.0 mL, 87.6 mmol) and trifluoroacetic acid (7.00 mL, 90.9 mmol) were added. The reaction was stirred at 80° C. for 4 hours, then solvents removed under vacuum, and the residue was combined with aqueous potassium carbonate and extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate, filtered and the filtrate concentrated under vacuum to provide the desired compound, which was used in the next step without further purification. MS (ESI) [M+H+]+=272.1.
Reaction SMILES: [ClH:1].[CH3:2][C:3]1[S:19][C:6]2[CH2:7][N:8]([CH3:18])[CH2:9][CH:10]([C:11]3[CH:16]=[CH:15][C:14]([Br:17])=[CH:13][CH:12]=3)[C:5]=2[CH:4]=1.[Br-:20].[Al+3].[Br-].[Br-].BrBr.N>C(O)(=O)C>[ClH:1].[CH3:2][C:3]1[S:19][C:6]2[CH2:7][N:8]([CH3:18])[CH2:9][CH:10]([C:11]3[CH:16]=[CH:15][C:14]([Br:17])=[CH:13][CH:12]=3)[C:5]=2[C:4]=1[Br:20]
Reactant: Cc1cc2c(s1)CN(C)CC2c1ccc(Br)cc1
Reactant: [Br-]
Agent: BrBr
Agent: Cl
Agent: N
Solvent: CC(=O)O
Product: Cc1sc2c(c1Br)C(c1ccc(Br)cc1)CN(C)C2
Temperature: 15 °C

Procedure:
3 gm (0.008 mol) of 2,6-dimethyl-4-(p-bromophenyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine hydrochloride and 8 gm of aluminum bromide were dissolved in 100 ml of glacial acetic acid. The solution was cooled to 15° C., 1.4 gm of bromine were slowly added dropwise and the mixture was stirred several hours until the reaction had gone to completion. Then, the mixture was decomposed with ice water, made alkaline with ammonia, extracted with ethyl acetate and evaporated. The residue was chromatographed on silicagel with methylene chloride/methanol (95:5). Upon addition of ethereal hydrochloric acid, 2.25 gm (61% of theory) of the title compound, m.p. 261°-262° C., were obtained.
Reaction SMILES: Cl[C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([OH:12])[CH:8]=2)[N:3]=1.CC1(C)C(C)(C)OB([C:21]2[CH2:26][CH2:25][CH:24]([C:27]([O:29][CH3:30])=[O:28])[CH2:23][CH:22]=2)O1>>[OH:12][C:7]1[CH:8]=[C:9]2[C:4](=[CH:5][CH:6]=1)[N:3]=[C:2]([C:21]1[CH2:26][CH2:25][CH:24]([C:27]([O:29][CH3:30])=[O:28])[CH2:23][CH:22]=1)[CH:11]=[CH:10]2
Reactant: Oc1ccc2nc(Cl)ccc2c1
Reactant: COC(=O)C1CC=C(B2OC(C)(C)C(C)(C)O2)CC1
Product: COC(=O)C1CC=C(c2ccc3cc(O)ccc3n2)CC1

Procedure:
Followed Scheme 3: Starting Materials: 2-chloroquinolin-6-ol and methyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)cyclohex-3-enecarboxylate.
Reaction SMILES: Br[CH:2]([CH2:19][CH3:20])[C:3]([NH:5][C:6]1[S:7][C:8]([CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[Cl:18])=[CH:9][N:10]=1)=[O:4].[NH:21]1[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]1>CN(C)C=O>[Cl:18][C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=1[CH2:11][C:8]1[S:7][C:6]([NH:5][C:3](=[O:4])[CH:2]([N:21]2[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]2)[CH2:19][CH3:20])=[N:10][CH:9]=1
Reactant: C1CCNCC1
Reactant: CCC(Br)C(=O)Nc1ncc(Cc2ccccc2Cl)s1
Solvent: CN(C)C=O
Product: CCC(C(=O)Nc1ncc(Cc2ccccc2Cl)s1)N1CCCCC1

Procedure:
2-Bromo-N-[5-(2-chloro-benzyl)-thiazol-2-yl]-butyramide (37 mg, 0.10 mmol) was dissolved in 0.5 mL of N,N-dimethylformamide containing piperidine (170 mg, 2.0 mmol). The reaction vessel was sealed and then subjected to microwave irradiation for 5 minutes at 80° C. The crude mixture was evaporated to dryness and purified by reverse-phase preparative liquid chromatography (31 mg, 0.082, 82%). ESI-MS m/z calc. 377.1, found 378.2 (M+1)+ Retention time 2.21 minutes.