Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [O:1]=[C:2]([C:8]1[CH:9]=[C:10]2[C:14](=[CH:15][CH:16]=1)[N:13]([CH3:17])[CH:12]1[N:18]([CH3:21])[CH2:19][CH2:20][C:11]21[CH3:22])[C:3]([O:5][CH2:6][CH3:7])=[O:4].[CH3:23][O:24][C:25]1[CH:30]=[CH:29]C(CO)=[CH:27][CH:26]=1>[O-]CC.[Ti+4].[O-]CC.[O-]CC.[O-]CC>[O:1]=[C:2]([C:8]1[CH:9]=[C:10]2[C:14](=[CH:15][CH:16]=1)[N:13]([CH3:17])[CH:12]1[N:18]([CH3:21])[CH2:19][CH2:20][C:11]21[CH3:22])[C:3]([O:5][CH2:6][C:7]1[CH:29]=[CH:30][C:25]([O:24][CH3:23])=[CH:26][CH:27]=1)=[O:4]
Reactant: COc1ccc(CO)cc1
Reactant: CCOC(=O)C(=O)c1ccc2c(c1)C1(C)CCN(C)C1N2C
Agent: [Ti+4]
Agent: CC[O-]
Product: COc1ccc(COC(=O)C(=O)c2ccc3c(c2)C2(C)CCN(C)C2N3C)cc1
Reaction time: 8 h

Procedure:
To a chilled (0° C.) solution of 1,2,3,3a,8,8a-hexahydro-α-oxo-1,3a,8-trimethyl-5-pyrrolo[2,3-b]indole acetic acid, ethyl ester (2.07 g) in anhydrous 4-methoxyphenylmethyl alcohol (40 ml) was added titanium (IV) ethoxide (0.54 ml) with stirring under nitrogen atmosphere. The reaction mixture was heated without reflexing for 8 hours. The 4-methoxyphenylmethyl alcohol was removed by distillation under high vacuum and the residue was dissolved in dichloromethane (200 ml). The residue was washed successively with two 100 ml portions of saturated aqueous NH4Cl solution, two 100 ml portions of saturated aqueous NaHCO3 solution and with brine, dried (Na2SO4), filtered and evaporated to yield an oil. The oil was purified by preparative HPLC (silica gel, 3% methanol in ethyl acetate as the loading solvent and eluent). A second preparative HPLC purification using 3% methanol in dichloromethane, yielded 1,2,3,3a,8,8a-hexahydro-α-oxo-1,3a,8-trimethyl-5-pyrrolo[2,3-b]indole acetic acid, 4-methoxyphenylmethyl ester (0.84 g) as an oil.
Reaction SMILES: [F:1][C:2]1([F:25])[CH2:7][CH2:6][CH2:5][C:4]([CH2:9][NH:10][C:11]([C:13]2[C:14]3[CH:15]=[CH:16][C:17](Cl)=[N:18][C:19]=3[CH:20]=[CH:21][C:22]=2[Cl:23])=[O:12])([OH:8])[CH2:3]1.CCN(C(C)C)C(C)C.[CH3:35][N:36]([CH3:42])[C@H:37]1[CH2:41][CH2:40][NH:39][CH2:38]1>>[F:1][C:2]1([F:25])[CH2:7][CH2:6][CH2:5][C:4]([CH2:9][NH:10][C:11]([C:13]2[C:14]3[CH:15]=[CH:16][C:17]([N:39]4[CH2:40][CH2:41][C@H:37]([N:36]([CH3:42])[CH3:35])[CH2:38]4)=[N:18][C:19]=3[CH:20]=[CH:21][C:22]=2[Cl:23])=[O:12])([OH:8])[CH2:3]1
Reactant: O=C(NCC1(O)CCCC(F)(F)C1)c1c(Cl)ccc2nc(Cl)ccc12
Reactant: CN(C)[C@H]1CCNC1
Solvent: CCN(C(C)C)C(C)C
Product: CN(C)[C@H]1CCN(c2ccc3c(C(=O)NCC4(O)CCCC(F)(F)C4)c(Cl)ccc3n2)C1

Procedure:
The title compound was synthesized according to the procedure described in example 1 using 2,6-dichloro-quinoline-5-carboxylic acid (3,3-difluoro-1-hydroxy-cyclohexylmethyl)-amide, DIPEA and (S)-3-dimethylamino-pyrrolidine. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.73 (m, 1H), 7.85 (1H), 7.48 (m, 2H), 6.69 (1H), 4.66 (s, 1H), 3.89 (m, 1H), 3.70 (m, 1H), 3.45 (m, 1H), 3.26 (m, 2H), 2.85 (m, 1H), 2.54 (m, 4H), 2.22 (s, 6H), 2.15 (m, 1H), 2.06 (m, 2H), 1.85 (m, 3H), 1.74-1.76 (m, 5H). m/z: 467 [M+H]
Reaction SMILES: [CH2:1]([O:3][C:4]1[N:9]=[C:8]([CH2:10][Cl:11])[CH:7]=[C:6]([OH:12])[N:5]=1)[CH3:2].[CH3:13][N:14]([CH3:18])[C:15](Cl)=[O:16]>>[CH3:13][N:14]([CH3:18])[C:15](=[O:16])[O:12][C:6]1[N:5]=[C:4]([O:3][CH2:1][CH3:2])[N:9]=[C:8]([CH2:10][Cl:11])[CH:7]=1
Reactant: CN(C)C(=O)Cl
Reactant: CCOc1nc(O)cc(CCl)n1
Product: CCOc1nc(CCl)cc(OC(=O)N(C)C)n1

Procedure:
2-Ethoxy-4-chloromethyl-6-hydroxy-pyrimidine is reacted with N,N-dimethylcarbamoyl chloride analogously to the process described in Example 87 in order to produce 2-ethoxy-4-chloromethyl-6-pyrimidinyl N,N-dimethylcarbamate which is required as the starting material in Example 33. This product is obtained in the form of a yellow oil, 1H-NMR (CDCl3): 1.43 (t, OCH2CH3), 3.08 and 3.14 (2×s, CON(CH3)2), 4.40 (q, OCH2CH3), 4.50 (s, CH2Cl), 7.00 (s, CH).
Reaction SMILES: [CH3:1][N:2]1[C:10]2[NH:11][C:12](=[O:19])[C:13]3[C:18]([C:9]=2[C:8]2[CH:7]=[C:6]([Cl:20])[CH:5]=[CH:4][C:3]1=2)=[CH:17][CH:16]=[CH:15][CH:14]=3.[H-].[Na+].[CH2:23]([O:25][CH2:26][CH2:27]Br)[CH3:24]>>[CH3:24][CH2:23][O:25][CH2:26][CH2:27][O:19][C:12]1[C:13]2[C:18](=[CH:17][CH:16]=[CH:15][CH:14]=2)[C:9]2[C:8]3[CH:7]=[C:6]([Cl:20])[CH:5]=[CH:4][C:3]=3[N:2]([CH3:1])[C:10]=2[N:11]=1
Reactant: CCOCCBr
Reactant: Cn1c2ccc(Cl)cc2c2c3ccccc3c(=O)[nH]c21
Agent: [H-]
Agent: [Na+]
Product: CCOCCOc1nc2c(c3ccccc13)c1cc(Cl)ccc1n2C

Procedure:
5-β-Ethoxyethyloxy-7-methyl-10-chloro-7H-indolo(2,3-c)isoquinoline (melting point 93.5°-95.5° C.) is prepared from 7-methyl-10-chloro-7H-indolo(2,3-c)isoquinolin-5(6H)-one, sodium hydride and β-ethoxyethyl bromide by the method described in Example 8.
Reaction SMILES: N[C:2]1[CH:13]=[CH:12][C:5]2[N:6]([CH3:11])[C:7](=[O:10])[CH2:8][O:9][C:4]=2[CH:3]=1.S(=O)(=O)(O)[OH:15].N([O-])=O.[Na+]>O>[OH:15][C:2]1[CH:13]=[CH:12][C:5]2[N:6]([CH3:11])[C:7](=[O:10])[CH2:8][O:9][C:4]=2[CH:3]=1
Reactant: O=S(=O)(O)O
Reactant: CN1C(=O)COc2cc(N)ccc21
Agent: O=N[O-]
Agent: [Na+]
Solvent: O
Product: CN1C(=O)COc2cc(O)ccc21
Temperature: 0 °C
Reaction time: 0.17 h
Yield: 32 %

Procedure:
To a cooled (0° C.) solution of 7-amino-4-methyl-2H-1,4-benzoxazin-3(4H)-one (10.0 g, 56 mmol) in water (80 mL) was added concentrated sulfuric acid (17 mL). After stirring at 0° C. for 10 min, a solution of sodium nitrite (4.1 g, 59 mmol) in water (10 mL) was added dropwise. After stirring for 0.5 h, the reaction mixture was added dropwise to a solution of cupric sulfate (50 g) in water (300 mL) at reflux. Once the addition was complete, the reaction mixture was allowed to cool to ambient temperature and was extracted with ethyl acetate (5×200 mL). The combined organic solution was dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was purified by trituration with ice-cold ethyl acetate (25 mL) and the solid was collected by vacuum filtration, air-dried and dried under high vacuum to afford 7-hydroxy-4-methyl-2H-1,4-benzoxazin-3(4H)-one (3.22 g, 32%) as a tan solid: 1H NMR (300 MHz, DMSO-d6) δ9.40 (s, 1H), 6.95 (d, J=8.7 Hz, 1H), 6.45 (dd, J=8.7, 2.6 Hz, 1H), 6.40 (d, J=2.6 Hz, 1H), 4.56 (s, 2H), 3.21 (s, 3H); MS (ES+) m/z 180.1 (M+1).
Reaction SMILES: [Al].[C:2]([C:6]1[CH:11]=[C:10]([C:12]([CH3:15])([CH3:14])[CH3:13])[C:9](=[O:16])[C:8](O)([C:17]([F:20])([F:19])[F:18])[CH:7]=1)([CH3:5])([CH3:4])[CH3:3]>O>[C:12]([C:10]1[CH:11]=[C:6]([C:2]([CH3:3])([CH3:4])[CH3:5])[CH:7]=[C:8]([C:17]([F:19])([F:20])[F:18])[C:9]=1[OH:16])([CH3:13])([CH3:14])[CH3:15]
Reactant: CC(C)(C)C1=CC(O)(C(F)(F)F)C(=O)C(C(C)(C)C)=C1
Agent: [Al]
Solvent: O
Product: CC(C)(C)c1cc(C(C)(C)C)c(O)c(C(F)(F)F)c1
Temperature: 25 °C
Yield: 72.2 %

Procedure:
A strip of aluminum foil weighing 293 mg (11 mmol) was amalgamated by immersion in a solution of 2% mercuric chloride in water for 15 sec., washed with absolute ethanol followed by diethyl ether, cut into small pieces, and added to a solution of 315 mg (1.1 mmol) of 4,6-di-tert-butyl-2-hydroxy-2-trifluoromethyl-3,5-cyclohexadien-1-one in 25 mL of 10% water--90% tetrahydrofuran. The resulting mixture was heated at 60°-70° C. for 2 hours, allowed to cool to room temperature, and filtered. The filter cake was washed with diethyl ether. Concentration of the combined filtrates gave a residue which was poured into 10 mL of water. The aqueous mixture was extracted with three 10 mL portions of dichloromethane. Combination, drying, and concentration of the organic layers gave a residue which was purified by PTLC (one 2 mm silica gel plate eluted with petroleum ether), affording 218 mg (73% yield) of 2,4-di-tert-butyl-6-trifluoromethylphenol.
Reaction SMILES: C(OC([N:8]1[CH2:13][CH2:12][C@H:11]([CH2:14][N:15]=[N+:16]=[N-:17])[C@H:10]([OH:18])[CH2:9]1)=O)(C)(C)C>ClCCl.Cl>[N:15]([CH2:14][C@H:11]1[CH2:12][CH2:13][NH:8][CH2:9][C@H:10]1[OH:18])=[N+:16]=[N-:17]
Reactant: CC(C)(C)OC(=O)N1CC[C@H](CN=[N+]=[N-])[C@H](O)C1
Agent: Cl
Solvent: ClCCl
Product: [N-]=[N+]=NC[C@H]1CCNC[C@H]1O

Procedure:
A solution of cis-4-azidomethyl-3-hydroxy-piperidine-1-carboxylic acid tert-butyl ester (1.4 mmol, 360 mg) in dichloromethane (1 mL) and 4N HCl (2 mL) was stirred at room temperature for 2 h. Solvent was evaporated to give cis-4-azidomethyl-piperidin-3-ol and was used without further purification.
Reaction SMILES: Br[C:2]1[CH:33]=[C:32]([F:34])[C:5]([CH2:6][S:7][C:8]2[N:9]([C:25]3[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=3)[C:10]([C:13]([C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[C:18]([O:23][CH3:24])[CH:17]=3)([CH3:15])[CH3:14])=[CH:11][N:12]=2)=[C:4]([F:35])[CH:3]=1.[CH3:36][N:37]([CH3:41])[CH2:38][C:39]#[CH:40].N1CCCC1>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].[Cu]I>[Cl:22][C:19]1[CH:20]=[CH:21][C:16]([C:13]([C:10]2[N:9]([C:25]3[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=3)[C:8]([S:7][CH2:6][C:5]3[C:32]([F:34])=[CH:33][C:2]([C:40]#[C:39][CH2:38][N:37]([CH3:41])[CH3:36])=[CH:3][C:4]=3[F:35])=[N:12][CH:11]=2)([CH3:15])[CH3:14])=[CH:17][C:18]=1[O:23][CH3:24]
Reactant: COc1cc(C(C)(C)c2cnc(SCc3c(F)cc(Br)cc3F)n2-c2ccc(F)cc2)ccc1Cl
Reactant: C#CCN(C)C
Agent: Cl[Pd]Cl
Agent: [Cu]I
Agent: [Fe+2]
Solvent: C1CCNC1
Product: COc1cc(C(C)(C)c2cnc(SCc3c(F)cc(C#CCN(C)C)cc3F)n2-c2ccc(F)cc2)ccc1Cl
Temperature: 80 °C
Yield: 94.8 %

Procedure:
To a solution of 2-(4-bromo-2,6-difluorobenzylthio)-5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazole (250 mg, 0.43 mmol, 1.0 eq), N,N-dimethylprop-2-yn-1-amine (0.07 mL, 0.64 mmol, 1.5 eq) and pyrrolidine (0.05 mL, 0.64 mmol, 1.5 eq) in dry, degassed DMF (2 mL) were added PdCl2(dppf)2 (16 mg, 0.022 mmol, 5 mol %) and CuI (8 mg, 0.043 mmol, 10 mol %). The reaction mixture was heated at 80° C. for 16 h, at which time LCMS showed complete consumption of starting material. The mixture was diluted with EtOAc, washed with brine, dried and concentrated. Purification by column chromatography (0 to 15% MeOH/DCM) furnished 238 mg (95% yield) of 3-(4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluorophenyl)-N,N-dimethylprop-2-yn-1-amine as a brown oil: MS (EI): 584 (MH+).
Reaction SMILES: [C:1]([NH:4][CH2:5][C@@H:6]1[O:10][C:9](=[O:11])[N:8]([C:12]2[CH:17]=[C:16]([F:18])[C:15]([N:19]3[CH2:24][CH2:23][C:22]([O:28][P:29](=[O:32])([OH:31])[OH:30])([CH2:25][O:26][CH3:27])[CH2:21][CH2:20]3)=[C:14]([F:33])[CH:13]=2)[CH2:7]1)(=[O:3])[CH3:2].[OH-].[Mg+2:35].[OH-]>O>[Mg+2:35].[C:1]([NH:4][CH2:5][C@@H:6]1[O:10][C:9](=[O:11])[N:8]([C:12]2[CH:17]=[C:16]([F:18])[C:15]([N:19]3[CH2:24][CH2:23][C:22]([O:28][P:29](=[O:30])([O-:31])[O-:32])([CH2:25][O:26][CH3:27])[CH2:21][CH2:20]3)=[C:14]([F:33])[CH:13]=2)[CH2:7]1)(=[O:3])[CH3:2]
Reactant: COCC1(OP(=O)(O)O)CCN(c2c(F)cc(N3C[C@H](CNC(C)=O)OC3=O)cc2F)CC1
Agent: [Mg+2]
Agent: [OH-]
Solvent: O
Product: COCC1(OP(=O)([O-])[O-])CCN(c2c(F)cc(N3C[C@H](CNC(C)=O)OC3=O)cc2F)CC1
Temperature: 7.5 °C
Reaction time: 2 h
Yield: 92 %

Procedure:
To a solution of phosphoric acid mono-(1-{4-[(S)-5-(acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2,6-difluorophenyl}-4-methoxymethyl-piperidin-4-yl)ester (5.0 g, 0.010mol) anhydrous methanol (50 ml) at 0-5° C., under argon, was added powdered anhydrous magnesium hydroxide (0.585 g, 0.010 mol) and water (5 ml) simultanously. The reaction mixture was stirred at 5-10° C. for 2 hours. The ice-bath was removed and the stirring continued further at 30-35° C. for 1 hour. The reaction mixture was filtered and the filtrate evaporated under reduced pressure. Acetone (25 ml) was added to the residue and triturated. The solvent was decanted. This procedure was repeated twice with acetone (50 ml). Acetone after the third trituration was decanted and the residue dried under reduced pressure to obtain the product as white solid, 4.9 g, in 92% yield, Mp>200° C. (dec); MF: C19H24F2MgN3O8P. Aqueous solubility at pH 7 was ˜2 mg/ml.
Reaction SMILES: [Cl:1][C:2]1[CH:21]=[CH:20][CH:19]=[C:18]([Cl:22])[C:3]=1[C:4]([NH:6][C:7]1[CH:8]=[CH:9][CH:10]=[C:11]2[C:16]=1[N:15]=[CH:14][C:13]([CH3:17])=[CH:12]2)=[O:5].BrN1C(=O)CCC1=O.N(C(C)(CC(C)(OC)C)C#N)=NC(C)(CC(OC)(C)C)C#N.BrCC1C=[N:57][C:58]2C(C=1)=CC=C[C:59]=2[NH:65][C:66](=O)C1C(Cl)=CC=CC=1Cl.N1C=CN=C1>C(Cl)(Cl)(Cl)Cl.C(Cl)CCl>[Cl:1][C:2]1[CH:21]=[CH:20][CH:19]=[C:18]([Cl:22])[C:3]=1[C:4]([NH:6][C:7]1[CH:8]=[CH:9][CH:10]=[C:11]2[C:16]=1[N:15]=[CH:14][C:13]([CH2:17][N:57]1[CH:58]=[CH:59][N:65]=[CH:66]1)=[CH:12]2)=[O:5]
Reactant: O=C(Nc1cccc2cc(CBr)cnc12)c1c(Cl)cccc1Cl
Reactant: Cc1cnc2c(NC(=O)c3c(Cl)cccc3Cl)cccc2c1
Agent: COC(C)(C)CC(C)(C#N)N=NC(C)(C#N)CC(C)(C)OC
Agent: O=C1CCC(=O)N1Br
Agent: c1c[nH]cn1
Solvent: ClCCCl
Solvent: ClC(Cl)(Cl)Cl
Product: O=C(Nc1cccc2cc(Cn3ccnc3)cnc12)c1c(Cl)cccc1Cl
Temperature: 60 °C
Reaction time: 2.5 h

Procedure:
A mixture of 8-(2,6-dichlorobenzoylamino)-3-methylquinoline (104 mg), N-bromosuccinimide (67.1 mg) and 2,2'-azobis(2,4-dimethyl-4-methoxyvaleronitrile) (20.1 mg) in carbon tetrachloride (3 ml) was refluxed for 2 hours. After cooling, the mixture was washed with water, saturated sodium bicarbonate solution and brine, dried over magnesium sulfate and evaporated in vacuo to give a residue containing 3-bromomethyl-8-(2,6-dichlorobenzoylamino)quinoline. The residue was dissolved in ethylene chloride, and imidazole (64.1 mg) was added thereto. After stirring for 2.5 hours at 60° C., the mixture was washed with water and brine, dried over magnesium sulfate and evaporated in vacuo. The residue was purified by column chromatography on silica gel (ethyl acetate-dichloromethane) to give 8-(2,6-dichlorobenzoylamino)-3-(imidazol-1-ylmethyl)quinoline (36.2 mg).
Reaction SMILES: [C:1]([N:4]1[C:8](=[O:9])[CH:7]=[CH:6][C:5]1=[O:10])(=[O:3])[NH2:2].[C:11]([O:16][CH2:17][CH2:18][OH:19])(=[O:15])[C:12]([CH3:14])=[CH2:13]>C(#N)C.[Cl-].[Zn+2].[Cl-]>[C:5]([OH:10])(=[O:15])/[CH:6]=[CH:7]\[C:8](=[O:9])[NH:4][C:1](=[O:3])[NH2:2].[C:11]([O:16][CH2:17][CH2:18][OH:19])(=[O:15])[C:12]([CH3:14])=[CH2:13]
Reactant: NC(=O)N1C(=O)C=CC1=O
Agent: C=C(C)C(=O)OCCO
Agent: [Cl-]
Agent: [Zn+2]
Solvent: CC#N
Product: NC(=O)NC(=O)/C=C\C(=O)O
Reaction time: 6 h
Yield: 138.8 %

Procedure:
A mixture of 140 g of N-carbamylmaleimide (1 mole), 130 g of 2-hydroxyethyl methacrylate (1 mole) and 1.36 g of zinc chloride (0.01 moles) in 200 mL of acetonitrile was heated to reflux. After 6 hours, the acetonitrile was evaporated and 500 mL of H2O was added. The solid was filtered and dried to afford 200 g (74% yield) of 2-hydroxyethyl methacrylate maleurate. M.P.: 62°-4° C. (dec.); 1H NMR (CDCl3): δ10.5 (br s, 1H), 8.2 (br s, 1H), 6.4 (m, 2H), 6.1 (m, 1H), 5.8 (br s, 1H), 5.6 (m, 1H), 4.4 (A2B2, 4H), 2.0 (m, 3H); 13C (CDCl3): δ167.1, 165.24, 165.23, 155.1, 135.8, 132.9, 129.6, 126.2, 63.2, 62.0, 18.2; HPLC (20% CH3CN/H2O, C18): Rt=3.5 minutes.
Reaction SMILES: FC(F)(F)C(O)=O.C(OC(=O)[NH:14][CH2:15][CH:16]1[CH2:21][CH2:20][N:19]([C:22]2[CH:27]=[CH:26][C:25]([C:28]([F:31])([F:30])[F:29])=[CH:24][CH:23]=2)[CH2:18][CH2:17]1)(C)(C)C>ClCCl>[F:30][C:28]([F:29])([F:31])[C:25]1[CH:24]=[CH:23][C:22]([N:19]2[CH2:20][CH2:21][CH:16]([CH2:15][NH2:14])[CH2:17][CH2:18]2)=[CH:27][CH:26]=1
Reactant: CC(C)(C)OC(=O)NCC1CCN(c2ccc(C(F)(F)F)cc2)CC1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: NCC1CCN(c2ccc(C(F)(F)F)cc2)CC1
Temperature: 25 °C
Reaction time: 3 h
Yield: 123.5 %

Procedure:
A mixture of trifluoroacetic acid (10 ml) and dichloromethane (10 ml) was added to tert-butyl({1-[4-(trifluoromethyl)phenyl]piperidin-4-yl}methyl)carbamate (1.36 g). This mixture was stirred at room temperature for 3 h. The sample was concentrated and taken up in dichloromethane (20 ml) and saturated aqueous sodium bicarbonate. The mixture was extracted and the organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo to provide the title compound (1.21 g, 86%). Mass spectrum (ESI) 242.1 (M+1).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:9](=NC2CCCCC2)[CH:10]=[C:11]2[CH2:15][CH2:14][CH2:13][NH:12]2)[CH:5]=[CH:6][C:7]=1[Cl:8].C([O-])(=O)/C=C/C([O-])=[O:27]>C(O)(C)C.CCOCC>[Cl:1][C:2]1[CH:3]=[C:4]([C:9](=[O:27])[CH:10]=[C:11]2[CH2:15][CH2:14][CH2:13][NH:12]2)[CH:5]=[CH:6][C:7]=1[Cl:8]
Reactant: O=C([O-])/C=C/C(=O)[O-]
Reactant: Clc1ccc(C(C=C2CCCN2)=NC2CCCCC2)cc1Cl
Solvent: CCOCC
Solvent: CC(C)O
Product: O=C(C=C1CCCN1)c1ccc(Cl)c(Cl)c1

Procedure:
With the use of 76.8 g (0.3 mole) of 3',4'-dichloro-2-(2-pyrrolidinylidene)-acetophenone, there is obtained in an analogous manner 2-[2-(3,4-dichlorophenyl)-2-(cyclohexylimino)-ethylidene]-pyrrolidine-(1:1)-fumarate, m.p. 208°-209° (from isopropanol/ether).
Reaction SMILES: [Cl:1][C:2]1[C:10]2[N:9]=[C:8]3[CH:11]([C:16]4[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][C:17]=4[Cl:23])[O:12][CH2:13][CH2:14][CH2:15][N:7]3[C:6]=2[C:5]([C:24]([CH:26]2[CH2:28][CH2:27]2)=[O:25])=[CH:4][CH:3]=1.[CH:29]1([Mg]Br)[CH2:31][CH2:30]1.C(OCC)(=O)C.[Cl-].[NH4+]>O1CCCC1>[Cl:1][C:2]1[C:10]2[N:9]=[C:8]3[CH:11]([C:16]4[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][C:17]=4[Cl:23])[O:12][CH2:13][CH2:14][CH2:15][N:7]3[C:6]=2[C:5]([C:24]([CH:29]2[CH2:31][CH2:30]2)([CH:26]2[CH2:28][CH2:27]2)[OH:25])=[CH:4][CH:3]=1
Reactant: Br[Mg]C1CC1
Reactant: O=C(c1ccc(Cl)c2nc3n(c12)CCCOC3c1ccc(Cl)cc1Cl)C1CC1
Agent: [Cl-]
Agent: [NH4+]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: OC(c1ccc(Cl)c2nc3n(c12)CCCOC3c1ccc(Cl)cc1Cl)(C1CC1)C1CC1
Reaction time: 0.25 h
Yield: 65 %

Procedure:
To a stirred solution of [10-chloro-1-(2,4-dichlorophenyl)-4,5-dihydro-1H,3H-[1,4]oxazepino[4,3-a]benzimidazol-7-yl](cyclopropyl)methanone (67.1 mg, 0.154 mmol) in tetrahydrofuran (1 mL) was added a solution of cyclopropyl magnesium bromide in tetrahydrofuran (1.0 M, 4.62 mL, 4.62 mmol) at 0° C. After 15 min, the reaction mixture was poured into a mixture of ethyl acetate and aqueous ammonium chloride. The organic phase was washed with brine, dried over sodium sulfate, filtrated, and concentrated in vacuo. The residue was purified by flash column chromatography on NH silica gel eluting with a 0-25% ethyl acetate/n-hexane gradient mixture to give the title compound as a colorless solid (48.2 mg, 0.101 mmol, 65%).
Reaction SMILES: [CH3:1][CH:2]1[CH2:18][CH2:17][O:16][C:14](=[O:15])[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][CH2:6][O:5][CH2:4][CH2:3]1.[CH3:19]C1CCOC(=O)CCCCCCOCC1.CC1CCOC(=O)CCCCCCCOCC1>>[CH3:1][C:2]1([CH3:19])[CH2:18][CH2:17][O:16][C:14](=[O:15])[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][CH2:6][O:5][CH2:4][CH2:3]1
Reactant: CC1CCOCCCCCCCCC(=O)OCC1
Reactant: CC1CCOCCCCCCC(=O)OCC1
Agent: CC1CCOCCCCCCCC(=O)OCC1
Product: CC1(C)CCOCCCCCCCCC(=O)OCC1

Procedure:
Odorant: relatively weak, fruity-musk like, reminiscent of ambrettone.--IR (film): ν=1734 cm-1 (νC=O), 1118/1150 cm-1 (νasO--C--C), 1242 cm-1 (νasC--C(=O), 1365 cm-1 (d CH3), 1055 cm-1 (νC--O--C).--1H-NMR (CDCl3): δ=0.95 (s, 6H, 13-Me2), 1.33-1.40 (m, 8H, 4-H2 -7-H2), 1.49-1.55 (m, 4H, 8-,12-H2), 1.62 (mc, 2H, 3-H2), 1.76 (t, J=8.0 Hz, 2H, 14-H2), 2.32 (t, J=6.4 Hz, 2H, 2-H2), 3.38 (t, J=5.2 Hz, 2H, 11-H2), 3.47 (t, J=5.8 Hz, 2H, 9-H2), 4.16 (t, J=8.0 Hz, 2H, 15-H2). --13C-NMR (CDCl3): δ=23.94/24.56 (t, C-3,-7), 25.84/26.36/26.52 (t, C-4,-5,-6), 28.04 (2q, 13-Me2), 29.23 (t, C-8), 31.79 (s, C-13), 34.53 (t, C-2), 39.02 (t, C-14), 41.28 (t, C-12), 61.98 (t, C-15), 67.82/70.49 (t, C-9,-11), 173.83 (s, C-1). --MS (EI): m/z (%)=55 (100) [C4H7⊕ ]69 (92) [C5H9⊕ ], 113 (39) ]C8H17⊕ ], 139 (29) [M⊕ --C7H15O2 ], 155 (18) [M⊕ --C7H15O2 ], 197 (3) [M⊕ --CO--C2H4O], 241 (2) [M⊕ --CO], 270 (1) [M⊕].--C16H30O3 (270.41): calculated C 71.07, H 11.18; found C 70.89, H 11.11.
Reaction SMILES: C(O[C:4](=[O:6])C)=O.[CH3:7][C:8]([N:15]([CH3:17])[CH3:16])([CH2:11][CH2:12][CH2:13][CH3:14])[CH2:9][NH2:10].[OH-].[Na+].CO>CCOCC>[CH3:7][C:8]([N:15]([CH3:16])[CH3:17])([CH2:11][CH2:12][CH2:13][CH3:14])[CH2:9][NH:10][CH:4]=[O:6]
Reactant: CC(=O)OC=O
Reactant: CCCCC(C)(CN)N(C)C
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: CCOCC
Product: CCCCC(C)(CNC=O)N(C)C
Reaction time: 8 h

Procedure:
To a solution of acetic formic anhydride (2.9 mls., 20 mmole) (prepared by stirring acetic anhydride [2.04 ml.] and formic acid [0.86 ml.] on a water bath at 50°-60° for two hrs. and cooling), was added dropwise, with stirring, 2-methyl-2-dimethylamino-hexylamine (2.37 g.,) at such a rate that the temperature never rose above 40°C. The solution was stirred for 30 mins. ether (6 ml) was added, and stirring continued at room temperature overnight. The mixture was diluted with ether (50 ml.), basified with 2N sodium hydroxide solution and extracted with ether (4 × 100 ml.). Evaporation of the washed (2 × 100 ml.), dried (Na2SO4) extracts gave a colourless oil (2.2 g.). T.L.C. (silica, methanol) showed two spots: RF 0.5 and RF 0.0. The oil was chromatographed on a column of silica (20 × 3.0 cm.) eluting with methanol and fractions (6 × 100 ml.) were collected. Fractions 2-5 were combined and evaporated affording N-[2-methyl-2-dimethylamino-hexyl]formamide as a colourless oil (1.427 g., 51%).
Reaction SMILES: [CH3:1][C:2]1[CH:13]=[C:12]2[C:5]([NH:6][CH:7]=[C:8]2[CH2:9][CH2:10][NH2:11])=[CH:4][CH:3]=1.[C:14](Cl)(=[O:16])[CH3:15]>>[CH3:1][C:2]1[CH:13]=[C:12]2[C:5](=[CH:4][CH:3]=1)[NH:6][CH:7]=[C:8]2[CH2:9][CH2:10][NH:11][C:14](=[O:16])[CH3:15]
Reactant: Cc1ccc2[nH]cc(CCN)c2c1
Reactant: CC(=O)Cl
Product: CC(=O)NCCc1c[nH]c2ccc(C)cc12

Procedure:
Working in the same manner as for the amidation reaction of Example 1, but using 5-methyltryptamine (Preparation 6) and acetyl chloride as reactants, the title compound is obtained.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[S:8]([N:11]1[C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=2[C:15](=[O:22])[CH2:14][CH2:13][CH2:12]1)(=[O:10])=[O:9].C(O[CH:28](N(C)C)[N:29]([CH3:31])[CH3:30])(C)(C)C>ClCCl>[CH3:28][N:29]([CH:31]=[C:14]1[C:15](=[O:22])[C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[N:11]([S:8]([C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=2[CH3:1])(=[O:10])=[O:9])[CH2:12][CH2:13]1)[CH3:30]
Reactant: Cc1ccccc1S(=O)(=O)N1CCCC(=O)c2ccccc21
Reactant: CN(C)C(OC(C)(C)C)N(C)C
Solvent: ClCCl
Product: Cc1ccccc1S(=O)(=O)N1CCC(=CN(C)C)C(=O)c2ccccc21

Procedure:
A mixture of 1.89 g of 1,2,3,4-tetrahydro-1-[(2-methylphenyl)sulfonyl]-5H-1-benzazepin-5-one and 2.47 ml of tert-butoxy-bis(dimethylamino)methane (Bredericks reagent) in 10 ml of dichloromethane is heated under argon on a steam bath for 16 hours. The mixture is concentrated to dryness under vacuum and the residue dissolved in CH2Cl2. The solution is filtered through a thin pad of hydrous magnesium silicate and the pad washed with 5% ethyl acetate in CH2Cl2. The filtrate is concentrated to dryness and the residue (1.96 g) crystallized from CH2Cl2 -hexane to give 0.85 g of crystals, m.p. 180°-185° C. A second crop of crystals (0.85 g) is recovered from the mother liquors and an additional 0.30 g is recovered from washing the pad of hydrous magnesium silicate with ethyl acetate.
Reaction SMILES: [CH2:1]([O:3][C:4]1[CH:10]=[CH:9][C:7]([NH2:8])=[CH:6][CH:5]=1)[CH3:2].[Cl:11][C:12]1[C:20]([N+:21]([O-:23])=[O:22])=[CH:19][C:18]([N+:24]([O-:26])=[O:25])=[C:17](Cl)[C:13]=1[C:14]([OH:16])=[O:15].C(N(CC)C(C)C)(C)C>C(#N)C>[Cl:11][C:12]1[C:20]([N+:21]([O-:23])=[O:22])=[CH:19][C:18]([N+:24]([O-:26])=[O:25])=[C:17]([NH:8][C:7]2[CH:9]=[CH:10][C:4]([O:3][CH2:1][CH3:2])=[CH:5][CH:6]=2)[C:13]=1[C:14]([OH:16])=[O:15]
Reactant: O=C(O)c1c(Cl)c([N+](=O)[O-])cc([N+](=O)[O-])c1Cl
Reactant: CCOc1ccc(N)cc1
Solvent: CCN(C(C)C)C(C)C
Solvent: CC#N
Product: CCOc1ccc(Nc2c([N+](=O)[O-])cc([N+](=O)[O-])c(Cl)c2C(=O)O)cc1
Temperature: 25 °C
Reaction time: 5 h

Procedure:
A solution of 10.5 g of 4-ethoxyaniline in 250 ml acetonitrile was added over a 1.5 hour period to a solution of 20 g of 2,6-dichloro-3,5-dinitrobenzoic acid and 11 g of N,N-diisopropylethylamine in 400 ml of acetonitrile and stirred at room temperature for five hours. After the solvent was removed in vacuo, the residue was dissolved in 500 ml of chloroform and extracted with several portions of 5% ammonium hydroxide. The aqueous extracts were washed with chloroform and acidified with dilute acid. The resulting solid was collected by filtration and was washed with water to provide 2-chloro-6-[(4-ethoxyphenyl)amino]-3,5-dinitrobenzoic acid, mp 202°-206° C.