Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [H-].[Na+].[CH3:3][N:4]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[C:7](=[O:14])[NH:6][C:5]1=[O:15].[C:16]([O:20][C:21](=[O:35])[C@H:22]([NH:27][C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:23][CH2:24][CH2:25]I)([CH3:19])([CH3:18])[CH3:17]>CN(C=O)C.C1OCCOCCOCCOCCOCCOC1>[C:16]([O:20][C:21](=[O:35])[C@H:22]([NH:27][C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:23][CH2:24][CH2:25][N:6]1[C:7](=[O:14])[C:8]2[C:13](=[CH:12][CH:11]=[CH:10][CH:9]=2)[N:4]([CH3:3])[C:5]1=[O:15])([CH3:17])([CH3:18])[CH3:19]
Reactant: Cn1c(=O)[nH]c(=O)c2ccccc21
Reactant: CC(C)(C)OC(=O)N[C@H](CCCI)C(=O)OC(C)(C)C
Agent: C1COCCOCCOCCOCCOCCO1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: Cn1c(=O)n(CCC[C@@H](NC(=O)OC(C)(C)C)C(=O)OC(C)(C)C)c(=O)c2ccccc21
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 94.4 %

Procedure:
Sodium hydride (0.408 g, 10.2 mmol) was added to a solution of 1,2,3,4-tetrahydro-1-methyl-2,4-dioxoquinazoline (2.17 g, 12.4 mmol) and 18-crown-6 (0.045 g) in 25 mL of DMF. After stirring at RT for 30 min, (2R)-(t-butyloxycarbonylamino)-5-iodopentanoic acid t-butyl ester (3.60 g, 9.02 mmol) in 15 mL of DMF was added, and the solution was stirred at RT for 30 min, then at 60° C. for 6 h. The solvent was removed under reduced pressure, and the residue was partitioned between ethyl acetate and 0.05M aqueous HCl. The organic phase was washed with water and brine, dried over MgSO4 and concentrated. The crude material was purified by silica gel chromatography (hexane/ethyl acetate 3/1˜2/1) to give the title compound (3.81 g, 95% yield): NMR (400 MHz, CDCl3) 1.42 (s, 9H), 1.45 (s, 9H), 1.60-1.88 (m, 4H), 3.60 (s, 3H), 4.08-4.21 (m, 3H), 5.06 (br d, 1H, J=8.1 Hz), 7.19-7.31 (m, 2H), 7.68 (dt, 1H, J=7.84, 1.56 Hz), 8.22 (dd, 1H, J=7.88, 1.52 Hz).
Reaction SMILES: [C:1]([NH:5][C:6]1[N:10]2[CH:11]=[CH:12][CH:13]=[CH:14][C:9]2=[N:8][C:7]=1[C:15]1[S:16][C:17]([C:20]#[C:21][Si](C)(C)C)=[CH:18][CH:19]=1)([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[K+].[K+].O>CO.C(Cl)Cl>[C:1]([NH:5][C:6]1[N:10]2[CH:11]=[CH:12][CH:13]=[CH:14][C:9]2=[N:8][C:7]=1[C:15]1[S:16][C:17]([C:20]#[CH:21])=[CH:18][CH:19]=1)([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)Nc1c(-c2ccc(C#C[Si](C)(C)C)s2)nc2ccccn12
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: ClCCl
Solvent: CO
Product: C#Cc1ccc(-c2nc3ccccn3c2NC(C)(C)C)s1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 97.4 %

Procedure:
11.5 g (31.3 mmol) of tert-butyl-[2-(5-trimethylsilanylethynyl-thiophen-2-yl)-imidazo[1,2-a]pyridin-3-yl]-amine were dissolved in a mixture of MeOH (230 ml) and DCM (50 ml) and combined with 431 mg (3.13 mmol) of potassium carbonate The reaction solution was stirred at RT for 30 min and then combined with water (200 ml). The mixture was then extracted with DCM and the organic phase was washed with water and dried over MgSO4. After filtration and evaporation under a vacuum, 9.0 g (30.5 mmol, 97%) of tert-butyl-[2-(5-ethynyl-thiophen-2-yl)-imidazo[1,2-a]pyridin-3-yl]-amine were obtained.
Reaction SMILES: [CH3:1][Si:2]([CH:5](O)[CH3:6])([CH3:4])[CH3:3].C1(N=C=NC2CCCCC2)CCCCC1.[NH2:23][C:24]1[S:25][CH:26]=[C:27]([CH2:29][C:30]([OH:32])=[O:31])[N:28]=1>CN(C)C1C=CN=CC=1.C(#N)C>[NH2:23][C:24]1[S:25][CH:26]=[C:27]([CH2:29][C:30]([O:32][CH2:6][CH2:5][Si:2]([CH3:4])([CH3:3])[CH3:1])=[O:31])[N:28]=1
Reactant: Nc1nc(CC(=O)O)cs1
Reactant: CC(O)[Si](C)(C)C
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: CN(C)c1ccncc1
Solvent: CC#N
Product: C[Si](C)(C)CCOC(=O)Cc1csc(N)n1
Reaction time: 48 h

Procedure:
11.2 g (15.8 ml, 0.1 mol) of trimethylsilylethanol, 100 mg of 4-dimethylaminopyridine and 11.4 g of dicyclohexylcarbodiimide are added at room temperature to 7.9 g (0.05 mol) of 2-aminothiazol-4-ylacetic acid in 50 ml of acetonitrile and the mixture is stirred for 2 days. The precipitated urea is then filtered off under suction, washed with ether, the washings are concentrated on a rotary evaporator and the residue is taken up in ether and the ethereal solution is washed with 0.5N hydrochloric acid and with NaHCO3 solution, dried over MgSO4 and concentrated on a rotary evaporator. After concentration of the solution and addition of petroleum ether, the desired ester crystallizes out.
Reaction SMILES: [CH3:1][C:2]1([CH3:36])[C:7](=[O:8])[NH:6][C:5]2[CH:9]=[C:10]([C:17]([N:19]([CH:33]([CH3:35])[CH3:34])[C@@H:20]3[CH2:25][CH2:24][CH2:23][N:22]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:21]3)=[O:18])[C:11]([C:13]([F:16])([F:15])[F:14])=[CH:12][C:4]=2[O:3]1.[CH2:37]([O:39][C:40](=[O:44])[CH2:41][CH2:42]Br)[CH3:38].C(=O)([O-])[O-].[K+].[K+].C(#N)C>O>[CH2:37]([O:39][C:40](=[O:44])[CH2:41][CH2:42][N:6]1[C:5]2[CH:9]=[C:10]([C:17]([N:19]([CH:33]([CH3:34])[CH3:35])[C@@H:20]3[CH2:25][CH2:24][CH2:23][N:22]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:21]3)=[O:18])[C:11]([C:13]([F:14])([F:15])[F:16])=[CH:12][C:4]=2[O:3][C:2]([CH3:36])([CH3:1])[C:7]1=[O:8])[CH3:38]
Reactant: CCOC(=O)CCBr
Reactant: CC(C)N(C(=O)c1cc2c(cc1C(F)(F)F)OC(C)(C)C(=O)N2)[C@@H]1CCCN(C(=O)OC(C)(C)C)C1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Solvent: O
Product: CCOC(=O)CCN1C(=O)C(C)(C)Oc2cc(C(F)(F)F)c(C(=O)N(C(C)C)[C@@H]3CCCN(C(=O)OC(C)(C)C)C3)cc21

Procedure:
To tert-Butyl (3R)-3-[{[2,2-dimethyl-3-oxo-7-(trifluoromethyl)-3,4-dihydro-2H-1,4-benzoxazin-6-yl]carbonyl}(isopropyl)amino]piperidine-1-carboxylate (460 mg) were added 3-bromopropionic acid ethyl ester (0.19 ml), potassium carbonate (298 mg) and acetonitrile (5 ml), and the mixture was refluxed for 5 hours. After the reaction was complete, water was added to the reaction solution, and the mixture was extracted with ethyl acetate solution. The obtained ethyl acetate solution was washed with water and an aqueous sodium chloride solution, dried over magnesium sulfate, filtered and concentrated. The obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate=1/1) to give the title compound (350 mg) as a colorless liquid.
Reaction SMILES: [F:1][C:2]1[CH:8]=[CH:7][C:6]([C:9]([F:12])([F:11])[F:10])=[CH:5][C:3]=1[NH2:4].C(N(CC)CC)C.ClC(Cl)(O[C:24](=[O:30])OC(Cl)(Cl)Cl)Cl.[F:32][C:33]1[CH:38]=[C:37]([B:39]2[O:43][C:42]([CH3:45])([CH3:44])[C:41]([CH3:47])([CH3:46])[O:40]2)[CH:36]=[CH:35][C:34]=1[NH2:48]>C(Cl)Cl.O>[F:32][C:33]1[CH:38]=[C:37]([B:39]2[O:43][C:42]([CH3:44])([CH3:45])[C:41]([CH3:47])([CH3:46])[O:40]2)[CH:36]=[CH:35][C:34]=1[NH:48][C:24]([NH:4][C:3]1[CH:5]=[C:6]([C:9]([F:10])([F:11])[F:12])[CH:7]=[CH:8][C:2]=1[F:1])=[O:30]
Reactant: CC1(C)OB(c2ccc(N)c(F)c2)OC1(C)C
Reactant: Nc1cc(C(F)(F)F)ccc1F
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Solvent: CCN(CC)CC
Solvent: O
Solvent: ClCCl
Product: CC1(C)OB(c2ccc(NC(=O)Nc3cc(C(F)(F)F)ccc3F)c(F)c2)OC1(C)C
Reaction time: 0.33 h
Yield: 38.2 %

Procedure:
8.55 g (48 mmol) of 2-fluoro-5-trifluoromethylaniline and 4.8 g (48 mmol) of triethylamine were dissolved in 30 mL of dry DCM and added dropwise to a solution of 4.7 g (16 mmol) of triphosgene in 30 mL of DCM at 5-10° C. Within 20 min TLC indicated full consumption of the starting amine. This mixture was treated dropwise with a solution of 11.3 g (48 mmol) of 2-fluoro-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenylamine and 4.8 g of triethylamine in 35 mL of DCM at room temperature. Then the reaction mixture was stirred for 2 h, poured into water, the organic layer was separated and evaporated. The residue was crystallized from 90% EtOH yielding 4.5 g of the target product. Flash column chromatography of the residue obtained from evaporation of the mother liquid yielded 2.7 g of the target material (combined yield 7.2 g; 34%).
Reaction SMILES: [NH:1]1[C:5]2=[N+:6]([O-])[CH:7]=[CH:8][CH:9]=[C:4]2[CH:3]=[CH:2]1.P(Cl)(Cl)([Cl:13])=O>>[Cl:13][C:9]1[CH:8]=[CH:7][N:6]=[C:5]2[C:4]=1[CH:3]=[CH:2][NH:1]2
Reactant: O=P(Cl)(Cl)Cl
Reactant: [O-][n+]1cccc2cc[nH]c21
Product: Clc1ccnc2[nH]ccc12
Reaction time: 1 h

Procedure:
A mixture of 1H-pyrrolo[2,3-b]pyridin-7-oxide (step 1)(10.0 g, 74.5 mmol) in phosphorous oxychloride (50 mL) was heated to reflux. After 12 h the excess phosphorous oxychloride was evaporated under reduced pressure and the residue was stirred in saturated aqueous sodium bicarbonate (250 mL) for one hour. The solid was collected by suction filtration, washed with water to neutrality, and air-dried to afford 9.8 g of 4-choro-7-azaindole as an off-white solid; MS (m/z) 153/155 (M+H).
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][CH:10]=1)[CH2:5]CO.Br[CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH3:25].[OH-:26].[Na+]>[Cl-].C([N+](CCCCCCCC)(CCCCCCCC)C)CCCCCCC.C1(C)C=CC=CC=1>[CH2:12]([O:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][CH:10]=1)[CH2:5][OH:26])[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH3:25]
Reactant: [OH-]
Reactant: CCCCCCCCCCCCCCBr
Reactant: OCCc1cccc(O)c1
Agent: CCCCCCCC[N+](C)(CCCCCCCC)CCCCCCCC
Agent: [Cl-]
Agent: [Na+]
Solvent: Cc1ccccc1
Product: CCCCCCCCCCCCCCOc1cccc(CO)c1
Yield: 652.2 %

Procedure:
A mixture of 66 g of 3-hydroxyphenethyl alcohol, 147.43 g of 1-bromotetradecane, 27.65 g of sodium hydroxide and 2.15 g of trioctylmethyl ammonium chloride in 400 ml of toluene was refluxed for 42 hours. The mixture was washed with water and the organic layer dried with magnesium sulfate. The solvent was removed in vacuo and the warm concentrate poured into 1 liter of hexanes. The resulting solid was washed with cold hexanes then dried giving 998.6 g of the desired compound as a white solid.
Reaction SMILES: Cl.[C:2]([CH2:4][NH:5][C:6]([C@@H:8]1[CH2:12][C@@H:11]([S:13]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[Cl:22])(=[O:15])=[O:14])[CH2:10][NH:9]1)=[O:7])#[N:3].[O:23]1[CH2:28][CH2:27][C:26](=O)[CH2:25][CH2:24]1>>[C:2]([CH2:4][NH:5][C:6]([C@@H:8]1[CH2:12][C@@H:11]([S:13]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[Cl:22])(=[O:14])=[O:15])[CH2:10][N:9]1[CH:26]1[CH2:27][CH2:28][O:23][CH2:24][CH2:25]1)=[O:7])#[N:3]
Reactant: N#CCNC(=O)[C@@H]1C[C@@H](S(=O)(=O)c2ccccc2Cl)CN1
Reactant: O=C1CCOCC1
Agent: Cl
Product: N#CCNC(=O)[C@@H]1C[C@@H](S(=O)(=O)c2ccccc2Cl)CN1C1CCOCC1

Procedure:
(2S,4R)-4-(2-chloro-benzenesulfonyl)-pyrrolidine-2-carboxylic acid cyanomethyl-amide hydrochloride from experiment K1 was reductively aminated with tetrahydro-4H-pyran-4-one in analogy to experiment L3 to give to give (2S,4R)-4-(2-chloro-benzenesulfonyl)-1-(tetrahydro-pyran-4-yl)-pyrrolidine-2-carboxylic acid cyanomethyl-amide as a colorless oil. MS: 412.1 [M+H]+.
Reaction SMILES: Br[CH2:2][C:3]([NH:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2([C:17]3[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=3)[O:16][CH2:15][CH2:14][O:13]2)=[CH:8][C:7]=1[CH:24]([C:26]1[CH:31]=[CH:30][CH:29]=[C:28]([Cl:32])[CH:27]=1)[OH:25])=[O:4].CC(O)(C)C.[K].Cl>COCCOC>[Cl:32][C:28]1[CH:27]=[C:26]([CH:24]2[C:7]3[CH:8]=[C:9]([C:12]4([C:17]5[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=5)[O:16][CH2:15][CH2:14][O:13]4)[CH:10]=[CH:11][C:6]=3[NH:5][C:3](=[O:4])[CH2:2][O:25]2)[CH:31]=[CH:30][CH:29]=1
Reactant: O=C(CBr)Nc1ccc(C2(c3ccc(Cl)cc3)OCCO2)cc1C(O)c1cccc(Cl)c1
Agent: Cl
Agent: [K]
Solvent: COCCOC
Solvent: CC(C)(C)O
Product: O=C1COC(c2cccc(Cl)c2)c2cc(C3(c4ccc(Cl)cc4)OCCO3)ccc2N1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 51.7 %

Procedure:
A mixture of intermediate (10) (0.072 mol) in DME (300 ml) was cooled on an ice bath. 2-methyl-2-propanol, potassium salt (0.144 mol) was added portionwise. The mixture was stirred at a low temperature for 30 min, at room temperature for 30 min, hydrolyzed and acidified with HCl. The precipitate was filtered off, rinced and dried, yielding 17 g (51.8%) of 5-(3-chlorophenyl)-7-[2-(4-chlorophenyl)-1,3-dioxolan-2-yl]-1,5-dihydro-4,1-benzoxazepin-2(3H)-one (intermediate 11), mp. 205° C.
Reaction SMILES: [S:1]1C=CC=C1CC(O)=O.[CH2:10]([O:17][CH2:18][CH:19]([O:22][C:23](=[O:25])[CH3:24])[CH:20]=[CH2:21])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.[CH3:26][CH2:27][O:28]CC>>[C:27]([S:1][CH2:21][CH2:20][CH:19]([O:22][C:23](=[O:25])[CH3:24])[CH2:18][O:17][CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)(=[O:28])[CH3:26]
Reactant: C=CC(COCc1ccccc1)OC(C)=O
Reactant: O=C(O)Cc1cccs1
Reactant: CCOCC
Product: CC(=O)OC(CCSC(C)=O)COCc1ccccc1
Temperature: 25 °C
Reaction time: 20 h
Yield: 64 %

Procedure:
A solution of thiolacetic acid (10.0 g., 0.13 mole) and 4-benzyloxy-3-acetoxy-1-butene (21.0 g., 0.096 mole) containing benzoxyl peroxide (50 mg.) is stirred at room temperature for 20 hours. The reaction mixture is taken up in ether (200 ml.), washed with saturated sodium bicarbonate solution until neutral and then with brine and dried over sodium sulfate. The ether is removed in vacuo and the resulting oil is purified by chromatography over silica gel using hexane-ethyl acetate (80-20) to elute. From the proper fraction there is obtained 18.0 g. (64%) of the title compound as a heavy oil.
Reaction SMILES: S(Cl)([Cl:3])=O.Cl.[NH2:6][CH:7]([CH2:11][S:12][C:13]([CH3:16])([CH3:15])[CH3:14])[C:8]([OH:10])=[O:9].[CH3:17][CH:18](O)[CH3:19]>>[ClH:3].[CH:18]([O:9][C:8](=[O:10])[CH:7]([NH2:6])[CH2:11][S:12][C:13]([CH3:16])([CH3:15])[CH3:14])([CH3:19])[CH3:17]
Reactant: O=S(Cl)Cl
Reactant: CC(C)O
Reactant: CC(C)(C)SCC(N)C(=O)O
Agent: Cl
Product: CC(C)OC(=O)C(N)CSC(C)(C)C
Yield: 82 %

Procedure:
Thionyl chloride (20 mL) was added to a solution of 14 (20.0 g, 93.6 mmol) in i-PrOH (160 mL) at 0° C. slowly. The reaction mixture was refluxed for 4 h, then cooled and concentrated. The residue was treated with ether (200 mL). The resulting ppt was collected by filtration, washed with ether, and air-dried to provide 16 as a white solid (19.7 g, 82%). 1H NMR (400 MHz, DMSO-d6) δ 8.78 (br s, 3H), 5.00 (m, 1H), 4.14 (t, 1H), 3.03 (m, 2H), 1.29 (s, 9H), 1.26 (d, 3H), 1.24 (d, 3H).
Reaction SMILES: [CH:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10]2[O:14][C:13](=[O:15])[N:12]([CH2:16][C:17]3[CH:26]=[CH:25][C:20]([C:21]([O:23]C)=[O:22])=[CH:19][CH:18]=3)[N:11]=2)=[CH:6][CH:5]=1)([CH3:3])[CH3:2].[I-].[Li+]>N1C=CC=CC=1.O>[CH:1]([C:4]1[CH:5]=[CH:6][C:7]([C:10]2[O:14][C:13](=[O:15])[N:12]([CH2:16][C:17]3[CH:18]=[CH:19][C:20]([C:21]([OH:23])=[O:22])=[CH:25][CH:26]=3)[N:11]=2)=[CH:8][CH:9]=1)([CH3:3])[CH3:2]
Reactant: COC(=O)c1ccc(Cn2nc(-c3ccc(C(C)C)cc3)oc2=O)cc1
Agent: [I-]
Agent: [Li+]
Solvent: O
Solvent: c1ccncc1
Product: CC(C)c1ccc(-c2nn(Cc3ccc(C(=O)O)cc3)c(=O)o2)cc1
Temperature: 25 °C
Yield: 65.4 %

Procedure:
Methyl 4-{[5-(4-isopropylphenyl)-2-oxo-1,3,4-oxadiazol-3(2H)-yl]methyl}benzoate (50 mg, 0.14 mmol) is refluxed with lithium iodide (0.19 g, 1.4 mmol) in pyridine (5 mL) for 48 h and the mixture is diluted with water (30 mL) after cooling to room temperature. The precipitate is collected by filtration, washed with dichloromethane and dried in the air to furnish the desired product 4-{[5-(4-isopropylphenyl)-2-oxo-1,3,4-oxadiazol-3(2H)-yl]methyl}benzoic acid (31 mg, 66%), m.p. 217-219° C. 1H NMR (CDCl3, 300 MHz) δ (ppm) 1.13 (d, 6H) 2.70-2.90 (m, 1H), 4.86 (s, 2H), 7.17 (d, 2H), 7.30 (d, 2H), 7.59 (d, 2H), 7.89 (d, 2H). MS (ES+): m/e 339.
Reaction SMILES: Cl[CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9](/[CH:12]=[CH:13]/[C:14]2[O:15][C:16]3[CH:22]=[CH:21][CH:20]=[CH:19][C:17]=3[N:18]=2)=[CH:8][CH:7]=1.[CH2:23]([NH:25][CH2:26][CH3:27])[CH3:24]>>[CH2:23]([N:25]([CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9](/[CH:12]=[CH:13]/[C:14]2[O:15][C:16]3[CH:22]=[CH:21][CH:20]=[CH:19][C:17]=3[N:18]=2)=[CH:8][CH:7]=1)[CH2:26][CH3:27])[CH3:24].[CH2:14]([NH:18][CH2:17][CH3:16])[CH3:13]
Reactant: ClCCCOc1ccc(/C=C/c2nc3ccccc3o2)cc1
Solvent: CCNCC
Product: CCN(CC)CCCOc1ccc(/C=C/c2nc3ccccc3o2)cc1

Procedure:
The title compound was prepared as described in Example 1 starting with (C) of Example 1 (2.0 g, 6.4 mmol) and using diethylamine in place of dibutylamine to produce 2.8 g (85% yield) diethylamine in place of dibutylamine to produce 2.8 g (85% yield) of the title compound as the HCl salt, mp 225°-226° C. IR(KBr): 1600 cm−1. MS: 351(MH+). 1H NMR (CD3 OD): δ 7.99-6.81 (m, 10H), 4.24 (t, J=5.7 Hz, 2H), 3.09 (m, 6H), 2.44 (m, 2H), 0.87 (m, 6H).
Reaction SMILES: [CH3:1][S:2][C:3]1[CH:10]=[CH:9][C:6]([CH2:7][Cl:8])=[CH:5][CH:4]=1.[C:11]1([P:17]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1>C1(C)C=CC=CC=1>[Cl-:8].[CH3:1][S:2][C:3]1[CH:10]=[CH:9][C:6]([CH2:7][P+:17]([C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=2)=[CH:5][CH:4]=1
Reactant: CSc1ccc(CCl)cc1
Reactant: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: Cc1ccccc1
Product: CSc1ccc(C[P+](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Product: [Cl-]
Temperature: 0 °C

Procedure:
A solution of 4-methylthiobenzyl chloride (3.1 g) and triphenylphosphine (4.72 g) was heated in toluene (35 mL) at reflux for 18 hr. The mixture was cooled to 0° C. and filtered. The resulting solid was used as such in the next step.
Reaction SMILES: [NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[N:2]1.[N:10]#[C:11][NH2:12].O.[C:14]1([CH3:24])[CH:19]=[CH:18][C:17]([S:20]([OH:23])(=[O:22])=[O:21])=[CH:16][CH:15]=1>O1CCOCC1.CCOCC>[C:14]1([CH3:24])[CH:15]=[CH:16][C:17]([S:20]([OH:23])(=[O:21])=[O:22])=[CH:18][CH:19]=1.[C:11]([N:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[N:2]1)(=[NH:10])[NH2:12]
Reactant: N#CN
Reactant: c1ccc2[nH]nnc2c1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: O
Solvent: C1COCCO1
Solvent: CCOCC
Product: N=C(N)n1nnc2ccccc21
Temperature: 25 °C

Procedure:
A mixture of benztriazole (11.9 g, 100 mmol), cyanamide (4.2 g, 100 mmol), and p-toluene sulfonic acid hydrate (19.2 g, 100 mmol) in dioxane was refluxed for 24 hours. The reaction mixture was allowed to cool to room temperature and was diluted with ether, stirred vigorously, then filtered. The filter cake was washed with ether and recrystallized from ethanol to give the desired product as a white solid.
Reaction SMILES: [Na+].[I-].CC(C)=[O:5].Br[C:8]12[CH2:17][CH:12]3[CH2:13][CH:14]([CH2:16][CH:10]([CH2:11]3)[C:9]1=[C:18]1[CH:25]3[CH2:26][CH:21]4[CH2:22][CH:23]([CH2:27][CH:19]1[CH2:20]4)[CH2:24]3)[CH2:15]2>O.O1CCOCC1>[OH:5][C:8]12[CH2:17][CH:12]3[CH2:13][CH:14]([CH2:16][CH:10]([CH2:11]3)[C:9]1=[C:18]1[CH:25]3[CH2:26][CH:21]4[CH2:22][CH:23]([CH2:27][CH:19]1[CH2:20]4)[CH2:24]3)[CH2:15]2
Reactant: BrC12CC3CC(CC(C3)C1=C1C3CC4CC(C3)CC1C4)C2
Reactant: CC(C)=O
Agent: [I-]
Agent: [Na+]
Solvent: C1COCCO1
Solvent: O
Product: OC12CC3CC(CC(C3)C1=C1C3CC4CC(C3)CC1C4)C2

Procedure:
The 4-eq.-bromoadamantylidene adamantane has bee found to have particularly advantageous and unexpected properties. Thus, unlike the corresponding 4-eq.-chloroadamantylidene adamantane, this compound permits carrying out substitution reactions by means of solvolysis without requiring an adjuvant such as an Ag+ salt. It has moreover been found that certain substituents can be introduced in one step where this had not been possible before. The 4-eq.-bromoadamantylidene adamantane reacts with primary and secondary alcohols to form ethers, with carboxylic acids to form esters, with primary amines to form secondary amines, and with nitriles to form N-adamantylidene adamantyl amides. Furthermore it has been found to be possible to carry out halogen exchange reactions with this compound, for example, in a reaction with NaI/acetone. Reaction of 4-eq.-bromoadamantylidene adamantane with H2O/dioxane gives a quantitative yield of 4-eq.-hydroxyadamantylidene adamantane. The solvolysis reactions are carried out in the pure reagent as the solvent or together with dioxane or DMF as a co-solvent.
Reaction SMILES: [NH2:1][C@H:2]1[CH2:7][C@@H:6]([C:8]([OH:10])=[O:9])[C@@H:5]([N:11]2[CH2:15][CH2:14][C@H:13]([NH:16][C:17]([O:19][CH2:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)=[O:18])[C:12]2=[O:27])[CH2:4][CH2:3]1.[CH3:28]N1CCOCC1.[CH3:35][C:36]([CH3:38])=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C=O>ClC(Cl)C.O>[CH2:20]([O:19][C:17]([NH:16][C@H:13]1[CH2:14][CH2:15][N:11]([C@H:5]2[CH2:4][CH2:3][C@@H:2]([N:1]([CH:36]([CH3:38])[CH3:35])[CH3:28])[CH2:7][C@H:6]2[C:8]([OH:10])=[O:9])[C:12]1=[O:27])=[O:18])[C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1
Reactant: N[C@@H]1CC[C@H](N2CC[C@H](NC(=O)OCc3ccccc3)C2=O)[C@H](C(=O)O)C1
Reactant: CN1CCOCC1
Reactant: CC(C)=O
Agent: C=O
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: CC(Cl)Cl
Solvent: O
Product: CC(C)N(C)[C@@H]1CC[C@H](N2CC[C@H](NC(=O)OCc3ccccc3)C2=O)[C@H](C(=O)O)C1
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 99.1 %

Procedure:
A stirring solution of (1R,2S,5R)-5-amino-2-((S)-3-(benzyloxycarbonylamino)-2-oxopyrrolidin-1-yl)cyclohexanecarboxylic acid (TFA salt, 35.5 g, 0.0725 mol) in dichloroethane (350 mL) was charged sequentially with N-methylmorpholine (29.3 g, 4.0 eq) and acetone (42.05 g, 10 eq). The mixture was stirred at room temperature for 10 min. and sodium triacetoxyborohydride (30.7 g, 2 eq) was added at 0° C. The mixture was stirred at room temperature for 14 h, then formaldehyde (37 wt % solution, 28.4 g, 5 eq) and sodium triacetoxyborohydride (18.4 g, 1.2 eq) were added. The mixture was stirred at room temperature for 2 h. Water (70 ml) was added and the stirring was continued for 10 minutes. The mixture was concentrated under reduced pressure to remove the organic solvents. The resulting mixture was adjusted pH to 7-8 with saturated NaHCO3 solution and then to pH˜6 with 1 N HCl. The mixture was extracted with dichloromethane (5×250 ml). The extracts were combined, dried over anhydrous Na2SO4, and concentrated under reduced pressure. The residue was dissolved in dichloromethane (100 ml) and the resultant solution was added dropwise to diethyl ether (1500 ml) with stirring. The solid formed was collected with filtration and washed with diethyl ether (3×50 ml). The white solid was dried in vacuo to give (1R,2S,5R)-2-((S)-3-(benzyloxycarbonylamino)-2-oxopyrrolidin-1-yl)-5-(isopropyl(methyl)amino)cyclohexanecarboxylic acid (31 g, 99%). The compound was used in the next step without further purification. LC/MS found [M+H]+=432.
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][CH2:5][N:6]1[C:10](=[O:11])[C:9]2=[CH:12][CH:13]=[CH:14][CH:15]=[C:8]2[C:7]1=[O:16].Cl.[CH3:18][C:19]1[CH:24]=[CH:23][C:22]([C:25]2[CH2:26][CH2:27][NH:28][CH2:29][CH:30]=2)=[CH:21][CH:20]=1.C(N(CC)CC)C>C(#N)C>[CH3:18][C:19]1[CH:20]=[CH:21][C:22]([C:25]2[CH2:30][CH2:29][N:28]([CH2:2][CH2:3][CH2:4][CH2:5][N:6]3[C:10](=[O:11])[C:9]4=[CH:12][CH:13]=[CH:14][CH:15]=[C:8]4[C:7]3=[O:16])[CH2:27][CH:26]=2)=[CH:23][CH:24]=1
Reactant: O=C1c2ccccc2C(=O)N1CCCCBr
Reactant: Cc1ccc(C2=CCNCC2)cc1
Agent: Cl
Solvent: CC#N
Solvent: CCN(CC)CC
Product: Cc1ccc(C2=CCN(CCCCN3C(=O)c4ccccc4C3=O)CC2)cc1
Yield: 88 %

Procedure:
A solution N-(4-bromobutyl)phthalimide (0.85 g), 4-(4-methylphenyl)-1,2,3,6-tetrahydropyridine hydrochloride (0.63 g) and triethylamine (0.91 g) in dry acetonitrile (10 ml) was refluxed for 3 hours. After evaporation of the solvent, crude residue was dissolved in ethyl acetate, washed with water, sat. ammonium chloride solution and brine successively, dried over magnesium sulfate and evaporated to give a yellow solid of N-[4-{4-(4-methylphenyl)-1,2,3,6-tetrahydropyridin-1-yl}butyl]phthalimide (0.99 g).