Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:12]=[C:11]2[C:6]([CH2:7][CH2:8][CH:9]([N:13]([CH:17]3[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]3)[CH2:14][CH2:15][CH3:16])[CH2:10]2)=[CH:5][CH:4]=1.C(N(CC)CC)C.[N:30]1([C:36](Cl)=[O:37])[CH2:35][CH2:34][O:33][CH2:32][CH2:31]1>>[CH3:1][O:2][C:3]1[CH:12]=[C:11]2[C:6]([CH2:7][CH2:8][CH:9]([N:13]([CH2:14][CH2:15][CH3:16])[CH:17]3[CH2:18][CH2:19][N:20]([C:36]([N:30]4[CH2:35][CH2:34][O:33][CH2:32][CH2:31]4)=[O:37])[CH2:21][CH2:22]3)[CH2:10]2)=[CH:5][CH:4]=1
Reactant: CCCN(C1CCNCC1)C1CCc2ccc(OC)cc2C1
Reactant: O=C(Cl)N1CCOCC1
Solvent: CCN(CC)CC
Product: CCCN(C1CCN(C(=O)N2CCOCC2)CC1)C1CCc2ccc(OC)cc2C1
Temperature: 25 °C
Reaction time: 4 h
Yield: 84.6 %

Procedure:
To an ice-cold solution of (7-methoxy-1,2,3,4-tetrahydro-naphthalen-2-yl)-piperidin-4-yl-propyl-amine (1.0 g, 3.3 mmol) and triethylamine (0.5 ml, 3.6 mmol) under an inert atmosphere was added morpholine-4-carbonyl chloride (0.4 mL, 3.5 mmol) dropwise. The ice bath was removed and the reaction stirred at room temperature for 4 h. The methylene chloride was washed 2 times with water (30 mL), dried (MgSO4), filtered, and concentrated to afford {4-[(7-methoxy-1,2,3,4-tetrahydro-naphthalen-2-yl)-propyl-amino]-piperidin-1-yl}-morpholin-4-yl-methanone as an oil (1.16 g).
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][CH2:4][CH:3]([NH:7][C:8]([C:10]2[C:14]3[N:15]=[CH:16][N:17]=[C:18]([C:19]4[C:27]5[O:26][CH2:25][O:24][C:23]=5[CH:22]=[CH:21][C:20]=4[O:28][CH2:29][CH2:30][CH2:31][CH3:32])[C:13]=3[NH:12][CH:11]=2)=[O:9])[CH2:2]1.[C:33](Cl)(=[O:36])[CH2:34][CH3:35]>>[C:33]([N:1]1[CH2:6][CH2:5][CH2:4][CH:3]([NH:7][C:8]([C:10]2[C:14]3[N:15]=[CH:16][N:17]=[C:18]([C:19]4[C:27]5[O:26][CH2:25][O:24][C:23]=5[CH:22]=[CH:21][C:20]=4[O:28][CH2:29][CH2:30][CH2:31][CH3:32])[C:13]=3[NH:12][CH:11]=2)=[O:9])[CH2:2]1)(=[O:36])[CH2:34][CH3:35]
Reactant: CCCCOc1ccc2c(c1-c1ncnc3c(C(=O)NC4CCCNC4)c[nH]c13)OCO2
Reactant: CCC(=O)Cl
Product: CCCCOc1ccc2c(c1-c1ncnc3c(C(=O)NC4CCCN(C(=O)CC)C4)c[nH]c13)OCO2

Procedure:
Starting from 4-(5-butoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxylic acid piperidin-3-ylamide (example A180) and propionyl chloride the title compound was obtained as colorless solid.
Reaction SMILES: Br[C:2]1[S:3][C:4]([Cl:19])=[CH:5][C:6]=1[CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18].C(C1C=CSC=1)CCCCCCCCCCC.BrN1C(=O)CCC1=O.BrC1SC=CC=1CCCCCCCCCCCC.ClN1C(=O)CCC1=O.[CH3:71][Si:72]([C:75]#[CH:76])([CH3:74])[CH3:73]>CN(C)C=O.C(N(CC)CC)C.[Cu]I>[Cl:19][C:4]1[S:3][C:2]([C:76]#[C:75][Si:72]([CH3:74])([CH3:73])[CH3:71])=[C:6]([CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18])[CH:5]=1
Reactant: C#C[Si](C)(C)C
Reactant: CCCCCCCCCCCCc1cc(Cl)sc1Br
Agent: [Cu]I
Agent: CCCCCCCCCCCCc1ccsc1
Agent: CCCCCCCCCCCCc1ccsc1Br
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: CCCCCCCCCCCCc1cc(Cl)sc1C#C[Si](C)(C)C

Procedure:
First, 2-bromo-5-chloro-3-dodecylthiophene can be prepared by brominating 3-dodecylthiophene with 1 molar equivalent of N-bromosuccinimide (NBS) in N,N-dimethylformamide (DMF) at room temperature (rt) (as used herein, “room temperature” refers, for example, to a temperature ranging from about 22° C. to about 25° C.). Next, the chlorination of 2-bromo-3-dodecylthiophene with 1 molar equivalent of N-chlorosuccinimide (NCS) at room temperature generates 2-bromo-5-chloro-3-dodecylthiophene. Subsequently, 2-bromo-5-chloro-3-dodecylthiophene is reacted with a trimethylsilylacetylene in the presence of dichlorobis(triphenylphosphine) palladium (II) (Pd(PPh3)2Cl2) and copper (I) iodide (CuI) in triethylamine (Et3N) at elevated temperatures, such as 50° C. for a suitable time like 24 hours, and 80° C. for 3 hours under argon to form 5-chloro-3-dodecyl-2-(trimethylsilyl)ethynylthiophene. 5-Chloro-3-dodecyl-2-(trimethylsilyl)ethynylthiophene is stirred in a mixture of methanol/dichloromethane (1/2, v/v) in the presence of 10 percent mol of potassium carbonate at room temperature for a suitable time like 16 hours to produce 5-chloro-3-dodecyl-2-ethynylthiophene. 5-Chloro-3-dodecyl-2-ethynylthiophene is then reacted with isopropylmagnesium chloride, and then with anthraquinone or 6,13-pentacenequinone at 50° C. in tetrahydrofuran (THF) under argon, followed by reduction with tin (II) chloride (SnCl2) solution in 10 percent HCl at elevated temperatures like 50° C. The resultant 9,10-bis(5-chloro-3-dodecylthienylethynyl)anthracene (M1) or 6,13-bis(5-chloro-3-dodecylthienylethynyl) pentacene (M2) is polymerized using zinc in the presence of nickel (II) chloride (NiCl2), 2,2′-dipyridil, triphenylphosphine (PPh3) in N,N-dimethylacetamide (DMAc) at elevated temperatures like 80° C. for a suitable time like 48 hours. Poly(9,10-bis(3-dodecylthienylethynyl)anthracene (6a) and poly(6,13-bis(3-dodecylthienylethynyl) pentacene (22a) are thus obtained.
Reaction SMILES: O.Cl.[NH2:3][C@H:4]([C:7]([OH:9])=[O:8])[CH2:5][SH:6].[OH-].[Na+].[CH2:12]([O:19][C:20]([N:22]1[CH2:27][CH2:26][CH:25]([CH2:28][CH2:29]I)[CH2:24][CH2:23]1)=[O:21])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1>C(O)C>[CH2:12]([O:19][C:20]([N:22]1[CH2:27][CH2:26][CH:25]([CH2:28][CH2:29][S:6][CH2:5][C@@H:4]([C:7]([OH:9])=[O:8])[NH2:3])[CH2:24][CH2:23]1)=[O:21])[C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1
Reactant: O=C(OCc1ccccc1)N1CCC(CCI)CC1
Reactant: N[C@@H](CS)C(=O)O
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Product: N[C@@H](CSCCC1CCN(C(=O)OCc2ccccc2)CC1)C(=O)O
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 68.2 %

Procedure:
In a nitrogen gas flow, 562 mg of L-cysteine hydrochloride monohydrate is dissolved in an aqueous solution of 2N sodium hydroxide. To the resulting solution, 5 ml of a tetrohydrofuran solution containing 1.2 g of 2-(1-benzyloxycarbonyl-4-piperidyl)ethyl iodide is added, and stirred for 1.5 hours at room temperature. Then, 3 ml of ethanol is further added, and stirred for 2 hours. The reaction solvent is distilled off under reduced pressure. To the residue, water and ether are added, and the mixture is shaken. The water layer is separated and adjusted to pH 5 with 2N aqueous hydrochloric acid to precipitate crystals. The crystals are recrystallized from methanol to give 0.8 g of S-[2-(1-benzyloxycarbonyl-4-piperidyl)ethyl]-L-cysteine having a melting point of 185° to 188° C.
Reaction SMILES: C[O:2][C:3](=[O:35])[CH2:4][O:5][C:6]1[C:15]([CH3:16])=[CH:14][C:13]([S:17][CH2:18][C:19]2[CH:24]=[CH:23][C:22]([C:25]3[CH:30]=[CH:29][C:28]([C:31]([F:34])([F:33])[F:32])=[CH:27][N:26]=3)=[CH:21][CH:20]=2)=[C:12]2[C:7]=1[CH2:8][CH2:9][CH2:10][O:11]2.COC(=O)COC1C(C)=CC(S)=C2C=1CCCO2.ClCC1C=CC(C2C=CC(C(F)(F)F)=CN=2)=CC=1.[K+].[Br-]>>[CH3:16][C:15]1[C:6]([O:5][CH2:4][C:3]([OH:35])=[O:2])=[C:7]2[C:12](=[C:13]([S:17][CH2:18][C:19]3[CH:20]=[CH:21][C:22]([C:25]4[CH:30]=[CH:29][C:28]([C:31]([F:34])([F:32])[F:33])=[CH:27][N:26]=4)=[CH:23][CH:24]=3)[CH:14]=1)[O:11][CH2:10][CH2:9][CH2:8]2
Reactant: COC(=O)COc1c(C)cc(SCc2ccc(-c3ccc(C(F)(F)F)cn3)cc2)c2c1CCCO2
Agent: COC(=O)COc1c(C)cc(S)c2c1CCCO2
Agent: FC(F)(F)c1ccc(-c2ccc(CCl)cc2)nc1
Agent: [Br-]
Product: Cc1cc(SCc2ccc(-c3ccc(C(F)(F)F)cn3)cc2)c2c(c1OCC(=O)O)CCCO2

Procedure:
{6-Methyl-8-[4-(5-trifluoromethyl-pyridine-2-yl)-benzylsulfanyl]-chroman-5-yloxy}-acetic acid methyl ester (compound 36A) The title compound was prepared in the manner analogous to Example 1F using (8-mercapto-6-methyl-chroman-5-yloxy)-acetic acid methyl ester and 18B. MS m/z 504 (M+1). Step 2. {6-Methyl-8-[4-(5-trifluoromethyl-pyridine-2-yl)-benzylsulfanyl]-chroman-5-yloxy}-acetic acid methyl ester (compound 36) The title compound was prepared in the manner analogous to Example 1 using 36A. mp 156-157° C.; IR (KBr) cm−1: 2928, 1731, 1710, 1603, 1329, 1113, 1082; 400 MHz 1H NMR (DMSO-d6): δ 12.84 (br(s), 1H), 8.97 (s, 1H), 8.22 (dd, 1H, J=8.4, 2.0 Hz), 8.12 (d, 1H, J=8.4 Hz), 8.04 (d, 2H, J=8.2 Hz), 7.42 (d, 2H, J=8.2 Hz), 6.88 (s, 1H), 4.29 (s, 2H), 4.05-4.14 (m, 4H), 2.64 (t, 2H, J=6.3 Hz), 2.04 (s, 3H), 1.81 (pentet, 2H); MS m/z 490 (M+1). Anal. Calc'd for C25H22F3NO4S: C, 61.34; H, 4.53; N, 2.86; found: C, 60.96; H, 4.48; N, 2.79.
Reaction SMILES: [CH3:1]C(C)([O-])C.[K+].[C:7]([C:10]1[CH:11]=[CH:12][C:13]([N:16]([CH2:34][C:35]2[CH:40]=[CH:39][C:38]([C:41]([F:44])([F:43])[F:42])=[CH:37][CH:36]=2)[CH2:17][CH2:18][C:19]2[CH:33]=[CH:32][C:22]([O:23][C:24]([CH3:31])([CH3:30])[C:25]([O:27][CH2:28][CH3:29])=[O:26])=[CH:21][CH:20]=2)=[N:14][CH:15]=1)(=O)[CH3:8]>[Br-].C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C1COCC1.C(O)(C)(C)C>[C:7]([C:10]1[CH:11]=[CH:12][C:13]([N:16]([CH2:34][C:35]2[CH:40]=[CH:39][C:38]([C:41]([F:42])([F:44])[F:43])=[CH:37][CH:36]=2)[CH2:17][CH2:18][C:19]2[CH:20]=[CH:21][C:22]([O:23][C:24]([CH3:31])([CH3:30])[C:25]([O:27][CH2:28][CH3:29])=[O:26])=[CH:32][CH:33]=2)=[N:14][CH:15]=1)([CH3:1])=[CH2:8]
Reactant: CCOC(=O)C(C)(C)Oc1ccc(CCN(Cc2ccc(C(F)(F)F)cc2)c2ccc(C(C)=O)cn2)cc1
Reactant: CC(C)(C)[O-]
Agent: C[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Br-]
Agent: [K+]
Solvent: CC(C)(C)O
Solvent: C1CCOC1
Product: C=C(C)c1ccc(N(CCc2ccc(OC(C)(C)C(=O)OCC)cc2)Cc2ccc(C(F)(F)F)cc2)nc1
Reaction time: 0.17 h
Yield: 30 %

Procedure:
A solution of methyltriphenylphosphonium bromide (101 mg; 0.28 mmol) in 0.76 ml of THF was treated under nitrogen with potassium tert-butoxide (0.28 ml of a 1M solution in tert-butanol). After 10 minutes, ethyl 2-[4-(2-{(5-acetylpyridin-2-yl)[4-(trifluoromethyl)benzyl]amino}ethyl)phenoxy]-2-methylpropanoate (100 mg; 0.19 mmol) was added. After 2 hours the reaction mixture was concentrated and the residue was partitioned between ethyl acetate and water. The organic phase was dried over sodium sulfate and concentrated. Purification by flash chromatography using 10% ethyl acetate-hexane mixtures afforded ethyl 2-[4-(2-{(5-isopropenylpyridin-2-yl)[4-(trifluoromethyl)benzyl]amino}ethyl)phenoxy]-2-methylpropanoate (30 mg; 30% yield).
Reaction SMILES: [C:1]([C:3]1[CH:4]=[C:5]([CH3:12])[C:6]([C:9]([OH:11])=O)=[N:7][CH:8]=1)#[N:2].C(Cl)(=O)C(Cl)=O.[NH2:19][C:20]1[N:25]=[C:24]([C@:26]2([CH3:44])[CH2:31][C@@H:30]([C:32]([F:35])([F:34])[F:33])[O:29][C:28]([NH:36][C:37](=[O:43])[O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[N:27]2)[C:23]([F:45])=[CH:22][CH:21]=1.C(N(CC)C(C)C)(C)C.C(C1C=C(C)C(C(Cl)=O)=NC=1)#N>C(Cl)Cl.C([O-])(O)=O.[Na+].CN(C=O)C>[C:1]([C:3]1[CH:4]=[C:5]([CH3:12])[C:6]([C:9]([NH:19][C:20]2[N:25]=[C:24]([C@:26]3([CH3:44])[CH2:31][C@@H:30]([C:32]([F:35])([F:33])[F:34])[O:29][C:28]([NH:36][C:37](=[O:43])[O:38][C:39]([CH3:40])([CH3:42])[CH3:41])=[N:27]3)[C:23]([F:45])=[CH:22][CH:21]=2)=[O:11])=[N:7][CH:8]=1)#[N:2]
Reactant: Cc1cc(C#N)cnc1C(=O)O
Reactant: CC(C)(C)OC(=O)NC1=N[C@](C)(c2nc(N)ccc2F)C[C@@H](C(F)(F)F)O1
Agent: Cc1cc(C#N)cnc1C(=O)Cl
Agent: O=C(Cl)C(=O)Cl
Agent: O=C([O-])O
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Solvent: CN(C)C=O
Product: Cc1cc(C#N)cnc1C(=O)Nc1ccc(F)c([C@]2(C)C[C@@H](C(F)(F)F)OC(NC(=O)OC(C)(C)C)=N2)n1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 47.5 %

Procedure:
To a solution of 5-cyano-3-methylpicolinic acid (intermediate 16, 0.050 g, 0.308 mmol) in DCM (2.5 mL) was added oxalyl chloride (0.040 mL, 0.463 mmol) and a drop of DMF. The reaction mixture was stirred for 30 min at room temperature. The reaction mixture was concentrated under reduced pressure and the residue was dissolved in DCM (1 mL). A flask was charged with a solution of tert-butyl ((4S,6S)-4-(6-amino-3-fluoropyridin-2-yl)-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-yl)carbamate (7k, 0.080 g, 0.204 mmol) and N,N-diisopropylethylamine (0.142 mL, 0.816 mmol, Aldrich) in DCM (2 mL). The solution of 5-cyano-3-methylpicolinoyl chloride was added and the reaction mixture was stirred at room temperature for 30 min, diluted with aqueous saturated NaHCO3 solution and extracted with EtOAc. The organic extract was washed with brine and dried over Na2SO4. The solution was concentrated under reduced pressure. The crude material was purified by silica gel chromatography (gradient of 5-50% EtOAc in hexane) to afford the title compound as a white solid (52 mg, 48% yield). MS m/z=537 [M+H]+. Calculated for C24H24F4N6O4: 536.
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[NH:7][C:8]([CH:19]=O)=[C:9]([CH2:12][CH2:13][C:14]([O:16][CH2:17][CH3:18])=[O:15])[C:10]=1[CH3:11])=[O:5])[CH3:2].[Cl:21][C:22]1[CH:23]=[C:24]2[C:28](=[CH:29][CH:30]=1)[NH:27][C:26](=[O:31])[CH2:25]2>N1CCCCC1.C(O)C>[CH2:1]([O:3][C:4]([C:6]1[NH:7][C:8]([CH:19]=[C:25]2[C:24]3[C:28](=[CH:29][CH:30]=[C:22]([Cl:21])[CH:23]=3)[NH:27][C:26]2=[O:31])=[C:9]([CH2:12][CH2:13][C:14]([O:16][CH2:17][CH3:18])=[O:15])[C:10]=1[CH3:11])=[O:5])[CH3:2]
Reactant: CCOC(=O)CCc1c(C=O)[nH]c(C(=O)OCC)c1C
Reactant: O=C1Cc2cc(Cl)ccc2N1
Solvent: C1CCNCC1
Solvent: CCO
Product: CCOC(=O)CCc1c(C=C2C(=O)Nc3ccc(Cl)cc32)[nH]c(C(=O)OCC)c1C
Yield: 85.7 %

Procedure:
5-Formyl-4-(2-ethoxycarbonylethyl)-3-methyl-1H-pyrrole-2-carboxylic acid ethyl ester (281 mg), 5-chloro-2-oxindole (168 mg), and piperidine (2 drops) in ethanol (2 mL) were refluxed for 2 hours. The reaction mixture was cooled and the precipitate that formed was filtered, washed with ethanol and hexanes, and dried to give 369 mg (86%) of 4-(2-ethoxycarbonylethyl)-3-methyl-5-(5-chloro-2-oxo-1,2-dihydro-indol-3-ylidenemethyl)-1H-pyrrole-2-carboxylic acid ethyl ester as a light yellow needle crystals.
Reaction SMILES: [OH:1][CH2:2][CH2:3][C:4]1[CH:16]=[CH:15][C:7]([O:8][CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])=[C:6]([O:17][CH3:18])[CH:5]=1.C(N(CC)CC)C.[C:26]1([CH3:36])[CH:31]=[CH:30][C:29]([S:32](Cl)(=[O:34])=[O:33])=[CH:28][CH:27]=1>ClCCl>[CH3:18][O:17][C:6]1[CH:5]=[C:4]([CH2:3][CH2:2][O:1][S:32]([C:29]2[CH:30]=[CH:31][C:26]([CH3:36])=[CH:27][CH:28]=2)(=[O:34])=[O:33])[CH:16]=[CH:15][C:7]=1[O:8][CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11]
Reactant: CCOC(=O)COc1ccc(CCO)cc1OC
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CCOC(=O)COc1ccc(CCOS(=O)(=O)c2ccc(C)cc2)cc1OC
Temperature: 25 °C
Reaction time: 24 h
Yield: 83 %

Procedure:
To a solution of ethyl 2-[4-(2-hydroxyethyl)-2-methoxyphenoxy]acetate (1.53 g) in dichloromethane (30 ml) were added triethylamine (1.26 ml) and p-toluenesulfonyl chloride (1.26 g), and the mixture was stirred for 24 hours at room temperature. The reaction mixture was washed with 1N hydrochloric acid and brine, and dried over anhydrous magnesium sulfate. After the solvent was removed under reduced pressure, purification of the residue by medium pressure liquid column chromatography on silica gel (eluent: hexane/ethyl acetate=3/2) gave ethyl 2-[2-methoxy-4-[2-(p-toluenesulfonyloxy)ethyl]phenoxy]acetate (2.04 g).
Reaction SMILES: [N+:1]([C:4]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:5]=1[CH:6]=[N:7][N:8]2[CH2:13][CH:14]1[CH2:19][CH2:18][CH2:17][N:16]([C:20](=[O:22])[CH3:21])[CH2:15]1)([O-])=O>CO.[Pd]>[NH2:1][C:4]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:5]=1[CH:6]=[N:7][N:8]2[CH2:13][CH:14]1[CH2:19][CH2:18][CH2:17][N:16]([C:20](=[O:22])[CH3:21])[CH2:15]1
Reactant: CC(=O)N1CCCC(Cn2ncc3c([N+](=O)[O-])cccc32)C1
Agent: [Pd]
Solvent: CO
Product: CC(=O)N1CCCC(Cn2ncc3c(N)cccc32)C1
Temperature: 25 °C
Reaction time: 8 h
Yield: 100.6 %

Procedure:
A solution of 1-(3-((4-nitro-1H-indazol-1-yl)methyl)piperidin-1-yl)ethanone (0.022 g, 0.073 mmol) in MeOH (1 mL) was purged with Argon, treated with 10% palladium on carbon (0.002 g) purged with more Argon, and then attached to a hydrogen balloon. The mixture was stirred at ambient temperature overnight, filtered through glass fiber filter paper, washed with MeOH and concentrated to give 1-(3-((4-amino-1H-indazol-1-yl)methyl)piperidin-1-yl)ethanone (0.020 g, 100% yield) as an amber oil.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][CH2:10][CH:9]1[CH2:14][C:15]([OH:17])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl:18][C:19]1[CH:20]=[C:21]([C:25]2NN=[N:27][N:26]=2)[CH:22]=[CH:23][CH:24]=1.C1(N=C=NC2CCCCC2)CCCCC1>>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][CH2:10][CH:9]1[CH2:14][C:15]1[O:17][C:25]([C:21]2[CH:22]=[CH:23][CH:24]=[C:19]([Cl:18])[CH:20]=2)=[N:26][N:27]=1)=[O:7])([CH3:2])([CH3:3])[CH3:4]
Reactant: CC(C)(C)OC(=O)N1CCCCC1CC(=O)O
Reactant: Clc1cccc(-c2nnn[nH]2)c1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Product: CC(C)(C)OC(=O)N1CCCCC1Cc1nnc(-c2cccc(Cl)c2)o1
Yield: 57.8 %

Procedure:
The title compound (1.21 g) was prepared from 2-carboxymethyl-piperidine-1-carboxylic acid tert butyl ester (1.35 g), 5-(3-chlorophenyl)tetrazole (1.0 g) and dicyclohexylcarbodiimide (1.15 g) according to the method of description 1.
Reaction SMILES: [BH4-].[Na+].[C:3]12([CH2:13][CH2:14][N:15]([CH2:25][CH2:26][CH2:27][CH2:28][CH3:29])[C:16](=[O:24])[CH2:17][O:18][CH2:19][C:20](OC)=[O:21])[CH2:12][CH:7]3[CH2:8][CH:9]([CH2:11][CH:5]([CH2:6]3)[CH2:4]1)[CH2:10]2.O.C(OCC)(=O)C>CO>[C:3]12([CH2:13][CH2:14][N:15]([CH2:25][CH2:26][CH2:27][CH2:28][CH3:29])[C:16](=[O:24])[CH2:17][O:18][CH2:19][CH2:20][OH:21])[CH2:10][CH:9]3[CH2:8][CH:7]([CH2:6][CH:5]([CH2:11]3)[CH2:4]1)[CH2:12]2
Reactant: CCCCCN(CCC12CC3CC(CC(C3)C1)C2)C(=O)COCC(=O)OC
Agent: [BH4-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: O
Solvent: CO
Product: CCCCCN(CCC12CC3CC(CC(C3)C1)C2)C(=O)COCCO
Temperature: 25 °C
Reaction time: 8 h
Yield: 21.9 %

Procedure:
Next, sodium borohydride (0.18 g, 4.8 mmol) was added to a solution of 2-methoxycarbonylmethoxyacetic acid N-[2-(1-adamantyl)ethyl]-N-pentylamide (0.37 g, 0.96 mmol) in methanol (3 ml) under ice-cooling, and the mixture was stirred at room temperature overnight. Water (10 ml) was added to the reaction mixture, and the whole was stirred for 10 minutes. Then, water (20 ml) and ethyl acetate (30 ml) were added thereto, and layers were separated. The organic layer was washed with a saturated aqueous sodium chloride solution (10 ml) and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was purified by silica gel column chromatography to give 74 mg (22%) of 2-(2-hydroxyethoxy)acetic acid N-[2-(1-adamantyl)ethyl]-N-pentylamide as an oily matter.
Reaction SMILES: [C:1]1([C:7]([CH:9]([CH2:13][CH2:14][C:15](=[O:17])[CH3:16])[C:10]([O-:12])=[O:11])=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:18](O)(=O)[CH3:19].CCOC(C)=O>C1(C)C=CC=CC=1.N1CCCCC1>[O:17]=[C:15]1[CH2:14][CH2:13][CH:9]([C:10]([O:12][CH2:18][CH3:19])=[O:11])[C:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)=[CH:16]1
Reactant: CC(=O)O
Reactant: CC(=O)CCC(C(=O)[O-])C(=O)c1ccccc1
Solvent: Cc1ccccc1
Solvent: CCOC(C)=O
Solvent: C1CCNCC1
Product: CCOC(=O)C1CCC(=O)C=C1c1ccccc1
Temperature: 25 °C
Yield: 758.3 %

Procedure:
A mixture of 2-(phenylcarbonyl)-5-oxohexanoate(3.87 g, 14.8 mmol), acetic acid(130 mg, 2.17 mmol) and piperidine(127 mg, 1.49 mmol) in toluene(5 ml) was refluxed for 5 hr. After cooling down to room temperature, AcOEt was added to the reaction mixture and washed with dil. HCl, water and brine and dried over MgSO4. After removal of the solvent, the residue was purified by column chromatography on silica gel with n-hexane-AcOEt to afford 4.02 g of ethyl 4-oxo-2-phenylcyclohex-2-enecarboxylate(y=94.7%) as a brown oil. 1H-NMR(ppm, 30 MHz, CDCl3) δ 7.50(2H, dd, J=3.0 and 6.4 Hz), 7.40-7.48(3H), 6.47(1H, s), 4.11(2H, q, J=7.0 Hz), 3.96(1H, dd, J=3.7 and 3.7 Hz), 2.60-2.70(1H, m), 2.35-2.55(3H), 1.12(3H, t, J=7.0 Hz)
Reaction SMILES: [CH3:1][C:2]1([CH3:32])[CH2:11][CH:10]=[C:9]([C:12]2[CH:17]=[CH:16][C:15]([CH3:18])=[CH:14][CH:13]=2)[C:8]2[CH:7]=[C:6]([C:19]#[C:20][C:21]3[CH:31]=[CH:30][C:24]([C:25]([O:27]CC)=[O:26])=[CH:23][CH:22]=3)[CH:5]=[CH:4][C:3]1=2.O[Li].O>O>[CH3:1][C:2]1([CH3:32])[CH2:11][CH:10]=[C:9]([C:12]2[CH:17]=[CH:16][C:15]([CH3:18])=[CH:14][CH:13]=2)[C:8]2[CH:7]=[C:6]([C:19]#[C:20][C:21]3[CH:22]=[CH:23][C:24]([C:25]([OH:27])=[O:26])=[CH:30][CH:31]=3)[CH:5]=[CH:4][C:3]1=2
Reactant: CCOC(=O)c1ccc(C#Cc2ccc3c(c2)C(c2ccc(C)cc2)=CCC3(C)C)cc1
Agent: [Li]O
Solvent: O
Product: Cc1ccc(C2=CCC(C)(C)c3ccc(C#Cc4ccc(C(=O)O)cc4)cc32)cc1

Procedure:
A solution of 142.6 mg (0.339 mmol) of ethyl 4-[(5,6-dihydro-5,5-dimethyl-8-(4-methylphenyl)-2-naphthalenyl)ethynyl]benzoate (Compound 1) and 35.6 mg (0.848 mmol) of LiOH-H2O in 12 ml of TBh/water (4:1, v/v), was stirred overnight at room temperature. The reaction mixture was extracted with hexanes, and the hexane fraction extracted with 5% aqueous NaOH. The aqueous layers were combined and acidified with 1M HCl, and then extracted with EtOAc and Et2O. The combined organic layers were dried over Na2SO4 and concentrated in vacuo to give the title compound as a colorless solid. 1H NMR (d6 -DMSO): δ 7.91 (2H, d, J=8.4 Hz); 7.60 (2H, d, J=8.4 Hz), 7.47 (2H, s), 7.23 (4H, q, J=8.1 Hz), 7.01 (1H, s), 6.01 (1H, t, J=4.6 Hz), 2.35 (3H, s), 2.33 (2H, d, J=4.8 Hz), 1.30 (6H, s).
Reaction SMILES: [C:1]([C:5]1[CH:10]=[CH:9][C:8]([CH:11]=[C:12]([N+:14]([O-])=O)[CH3:13])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[H-].[Al+3].[Li+].[H-].[H-].[H-].S([O-])([O-])(=O)=O.[Na+].[Na+]>O1CCCC1>[NH2:14][CH:12]([CH3:13])[CH2:11][C:8]1[CH:9]=[CH:10][C:5]([C:1]([CH3:4])([CH3:3])[CH3:2])=[CH:6][CH:7]=1
Reactant: CC(=Cc1ccc(C(C)(C)C)cc1)[N+](=O)[O-]
Agent: O=S(=O)([O-])[O-]
Agent: [Al+3]
Agent: [H-]
Solvent: C1CCOC1
Product: CC(N)Cc1ccc(C(C)(C)C)cc1
Yield: 74.2 %

Procedure:
A solution of 1-(4-t-butylphenyl)-2-nitroprop-1-ene (2.19 g, 10 mmol) in tetrahydrofuran (50ml) was added, over a period of 20 minutes, to a solution of lithium aluminium hydride (1.14 g, 30 mmol) in tetrahydrofuran (50 ml). The reaction mixture was then heated under reflux for 20 hours, cooled and worked up with saturated aqueous sodium sulphate solution. The mixture was filtered through Hyflo (Trade mark; diatomaceous earth) and the pad washed well with ethyl acetate. Evaporation in vacuo followed by flash column chromatography upon silica gel using 85:10:5 - ethyl acetate: methanol: triethylamine as eluant afforded 1.42 g 2-amino-1-(4-t-butylphenyl)propane as a clear, colourless oil. Low resolution mass spectroscopy revealed the mass/charge ratio of the parent molecule ion, M+, to be 191 thereby confirming the molecular weight of the product to be 191.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[N:9]([CH:11]1CC[CH2:13][CH2:12]1)[N:8]=[C:7]2[C:16]1[CH:21]=[CH:20][C:19]([O:22]C)=[CH:18][C:17]=1[CH3:24].B(Br)(Br)Br.C1CCCCC=1>>[CH2:11]([N:9]1[C:10]2[C:6](=[CH:5][CH:4]=[CH:3][C:2]=2[Cl:1])[C:7]([C:16]2[CH:21]=[CH:20][C:19]([OH:22])=[CH:18][C:17]=2[CH3:24])=[N:8]1)[CH:12]=[CH2:13]
Reactant: COc1ccc(-c2nn(C3CCCC3)c3c(Cl)cccc23)c(C)c1
Agent: BrB(Br)Br
Solvent: C1=CCCCC1
Product: C=CCn1nc(-c2ccc(O)cc2C)c2cccc(Cl)c21
Yield: 100.4 %

Procedure:
Prepared according to Method D step C from 7-chloro-1-cyclopentyl-3-(4-methoxy-2-methylphenyl)-1H-indazole (0.102 g, 0.33 mmol), boron tribromide (0.19 mL, 2.0 mmol) and 1.0 mL of cyclohexene to give the product (0.099 g) as a white solid.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]([F:12])([F:11])[F:10])=[CH:5][C:4]=1[Li].[CH3:14][N:15]1[C:19](=[O:20])[CH2:18][CH2:17][C:16]1=[O:21].[Cl-].[NH4+]>CCOCC.C1C=CC=CC=1>[CH3:14][NH:15][C:16](=[O:21])[CH2:17][CH2:18][C:19](=[O:20])[C:4]1[CH:5]=[C:6]([C:9]([F:12])([F:11])[F:10])[CH:7]=[CH:8][C:3]=1[O:2][CH3:1]
Reactant: CN1C(=O)CCC1=O
Reactant: [Li]c1cc(C(F)(F)F)ccc1OC
Agent: [Cl-]
Agent: [NH4+]
Solvent: CCOCC
Solvent: c1ccccc1
Product: CNC(=O)CCC(=O)c1cc(C(F)(F)F)ccc1OC
Reaction time: 8 h

Procedure:
A solution of 2-methoxy-5-trifluoromethylphenyllithium in ether was added to a cold stirred solution of N-methylsuccinimide in benzene. The resultant mixture was allowed to stand overnight and was then decomposed with ammonium chloride solution to give N-methyl 3-(2-methoxy-5-trifluoromethylbenzoyl)propionamide.