Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: FC(F)(F)S(O[C:7]1[CH:12]=[CH:11][C:10]([CH2:13][O:14][C:15]2([CH3:18])[CH2:17][CH2:16]2)=[C:9]([CH:19]([CH3:21])[CH3:20])[CH:8]=1)(=O)=O.[CH3:24][Si:25]([C:28]#[CH:29])([CH3:27])[CH3:26]>C(N(CC)CC)C.CN(C=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH:19]([C:9]1[CH:8]=[C:7]([C:29]#[C:28][Si:25]([CH3:27])([CH3:26])[CH3:24])[CH:12]=[CH:11][C:10]=1[CH2:13][O:14][C:15]1([CH3:18])[CH2:17][CH2:16]1)([CH3:21])[CH3:20]
Reactant: CC(C)c1cc(OS(=O)(=O)C(F)(F)F)ccc1COC1(C)CC1
Reactant: C#C[Si](C)(C)C
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: CC(C)c1cc(C#C[Si](C)(C)C)ccc1COC1(C)CC1
Temperature: 95 °C
Yield: 107.7 %

Procedure:
Using General Procedure D; 3-isopropyl-4-(1-methyl-cyclopropoxymethyl)-phenyl 1,1,1-trifluoromethanesulfonate (Intermediate 164, 120.0 mg, 0.34 mmol) in triethylamine (2 mL) and anhydrous DMF (5 mL) was sparged with argon for 5 minutes. Trimethylsilyl acetylene (700.0 mg, 0.71 mmol) was then added followed by dichlorobis(triphenylphosphine)palladium(II) (24.0 mg, 0.03 mmol). The resulting reaction mixture was heated to 95° C. for 60 hours. The title compound 110.0 mg, (99%) was isolated by chromatography (0-1% EtOAc-hexanes).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[CH:4][C:5]2[O:10][CH2:9][C:8](=[O:11])[NH:7][C:6]=2[CH:12]=1.Cl[CH2:14][C:15]([N:17]1[CH2:22][CH2:21][CH:20]([CH2:23][C:24]2[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=2)[CH2:19][CH2:18]1)=[O:16]>C(OCC)C>[F:30][C:27]1[CH:28]=[CH:29][C:24]([CH2:23][CH:20]2[CH2:21][CH2:22][N:17]([C:15](=[O:16])[CH2:14][NH:1][C:2]3[CH:3]=[CH:4][C:5]4[O:10][CH2:9][C:8](=[O:11])[NH:7][C:6]=4[CH:12]=3)[CH2:18][CH2:19]2)=[CH:25][CH:26]=1
Reactant: O=C(CCl)N1CCC(Cc2ccc(F)cc2)CC1
Reactant: Nc1ccc2c(c1)NC(=O)CO2
Solvent: CCOCC
Product: O=C1COc2ccc(NCC(=O)N3CCC(Cc4ccc(F)cc4)CC3)cc2N1

Procedure:
The title compound is prepared from 6-amino-4H-benzo[1,4]oxazin-3-one and 2-chloro-1-[4-(4-fluoro-benzyl)-piperidin-1-yl]-ethanone (Example 197a) according to the method described in Example 142b. Melting Point: 220-223° C. (diethylether)
Reaction SMILES: C(O)C.[OH-].[K+].C([O:9][C:10]1[CH:15]=[C:14]([O:16][CH2:17][CH2:18][CH2:19][CH3:20])[CH:13]=[CH:12][C:11]=1[O:21][CH2:22][CH2:23][CH2:24][CH3:25])(=O)C>O>[CH2:22]([O:21][C:11]1[CH:12]=[CH:13][C:14]([O:16][CH2:17][CH2:18][CH2:19][CH3:20])=[CH:15][C:10]=1[OH:9])[CH2:23][CH2:24][CH3:25]
Reactant: CCCCOc1ccc(OCCCC)c(OC(C)=O)c1
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: CCCCOc1ccc(OCCCC)c(O)c1
Reaction time: 1 h

Procedure:
23 [ml] of ethanol, 51.1 [g] of potassium hydroxide and 53.0 [g] of 2-acetoxy-1,4-di-n-butoxybenzene were added to 255 [ml] of water, and the mixture was reacted at 80° C. while stirring for 1 hour. After cooling the reaction liquor, it was neutralized and extracted twice with 200 [ml] of ethyl acetate. The extraction solution (i.e. the ethyl acetate solution) was washed with water, and concentrated by evaporating off the ethyl acetate as solvent under reduced pressure. Concentration of the extraction solution was continued until there was effectively no further evaporation of ethyl acetate (i.e., effectively no further ethyl acetate remained in the extraction solution). The separated crystals were filtered using filter paper, washed with a small amount of ethyl acetate, and dried to obtain 35.1 [g] of 2,5-di-n-butoxyphenol.
Reaction SMILES: [C:1]12([C:11]3[CH:12]=[C:13]([C:19]4([CH3:32])[C:23]5[CH:24]=[CH:25][C:26]([C:28]([O:30]C)=[O:29])=[CH:27][C:22]=5[O:21][CH2:20]4)[CH:14]=[CH:15][C:16]=3[O:17][CH3:18])[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2.[OH-].[Na+].[OH-].[Li+]>>[C:1]12([C:11]3[CH:12]=[C:13]([C:19]4([CH3:32])[C:23]5[CH:24]=[CH:25][C:26]([C:28]([OH:30])=[O:29])=[CH:27][C:22]=5[O:21][CH2:20]4)[CH:14]=[CH:15][C:16]=3[O:17][CH3:18])[CH2:10][CH:5]3[CH2:4][CH:3]([CH2:9][CH:7]([CH2:6]3)[CH2:8]1)[CH2:2]2
Reactant: COC(=O)c1ccc2c(c1)OCC2(C)c1ccc(OC)c(C23CC4CC(CC(C4)C2)C3)c1
Agent: [Li+]
Agent: [Na+]
Agent: [OH-]
Product: COc1ccc(C2(C)COc3cc(C(=O)O)ccc32)cc1C12CC3CC(CC(C3)C1)C2

Procedure:
A mixture of methyl 3-[3-(1-adamantyl)-4-methoxyphenyl]-3-methyl-2H-1-benzofuran-6-carboxylate (62 mg, 0.14 mmol), sodium hydroxide (0.012 g, 0.3 mmol) and lithium hydroxide (0.012 g, 0.28 mmol) is refluxed for 6 h. The mixture is concentrated on a rotary evaporator under vacuum at 40° C. 10 ml of water and 10 ml of ethyl acetate are added. The mixture is acidified with concentrated hydrochloric acid solution to pH=1. After separation of the phases by settling, the organic phase is washed twice with 10 ml of water, dried over magnesium sulphate and concentrated on a rotary evaporator under vacuum at 40° C. The product is purified by flash chromatography on a column of silica (50% CH2Cl2 50% EtOAc).
Reaction SMILES: [CH2:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][NH:2]1.[CH3:10][O:11][C:12]1[CH:17]=[CH:16][C:15]([N:18]=[C:19]=[O:20])=[C:14]([CH3:21])[CH:13]=1>O1CCOCC1>[CH3:10][O:11][C:12]1[CH:17]=[CH:16][C:15]([NH:18][C:19]([N:2]2[CH2:3][C:4]3[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=3)[CH2:1]2)=[O:20])=[C:14]([CH3:21])[CH:13]=1
Reactant: c1ccc2c(c1)CNC2
Reactant: COc1ccc(N=C=O)c(C)c1
Solvent: C1COCCO1
Product: COc1ccc(NC(=O)N2Cc3ccccc3C2)c(C)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 104.5 %

Procedure:
To a solution of isoindoline (576 mg, 4.0 mmol) in dry 1,4-dioxane (20 mL) was added 4-methoxy-2-methylphenyl isocyanate (815 mg, 5.0 mmol) under argon at room temperature. The reaction mixture was then stirred at RT overnight. The solvent was evaporated under reduced pressure, and the residue was purified by chromatography on silica gel (EtOAc/hexanes: 1:1) to give the title compound (1.18 g, 84%) as a white solid.
Reaction SMILES: [BH4-].[Na+].C(O)(=O)[C@H]([C@@H](C(O)=O)O)O.[CH3:13][O:14][C:15](=[O:33])[CH2:16][C:17](=[O:32])[C@@H:18]([O:26][SiH2:27][C:28]([CH3:31])([CH3:30])[CH3:29])[CH:19]=[CH:20][CH2:21][CH2:22][CH2:23][CH2:24][CH3:25].Cl.[Cl-].[Na+]>C1COCC1.C(OCC)(=O)C>[OH:32][C@@H:17]([C@@H:18]([O:26][SiH2:27][C:28]([CH3:29])([CH3:31])[CH3:30])[CH:19]=[CH:20][CH2:21][CH2:22][CH2:23][CH2:24][CH3:25])[CH2:16][C:15]([O:14][CH3:13])=[O:33]
Reactant: CCCCCC=C[C@H](O[SiH2]C(C)(C)C)C(=O)CC(=O)OC
Agent: Cl
Agent: O=C(O)[C@@H](O)[C@H](O)C(=O)O
Agent: [BH4-]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: CCCCCC=C[C@H](O[SiH2]C(C)(C)C)[C@H](O)CC(=O)OC
Temperature: -20 °C
Reaction time: 40 h
Yield: 93 %

Procedure:
NaBH4 (2.42 g, 64 mmol) was added in portions to a solution of D-tartaric acid (9.6 g, 64 mmol) in dry THF (150 ml), and the suspension thus obtained was heated at reflux temperature for 2.5 h and then cooled to −20° C. A solution of (4S)-methyl-3-oxo-4-tert-butylsilyloxyundec-5-enoate (7.54 g, 16 mmol) in dry THF (75 ml) was then added dropwise, the temperature remaining at −20° C. After 40 h, hydrochloric acid (1M, 150 ml) was added to the reaction mixture, on account of which the temperature increased to room temperature. The mixture was stirred for a further 15 minutes. Ethyl acetate (500 ml), followed by solid sodium chloride, was then introduced until the saturation point was reached. The aqueous phase was separated off and extracted with a further 200 ml of ethyl acetate. The organic phases were combined, washed twice with 150 ml in each case of saturated sodium bicarbonate solution and then with 100 ml of a saturated sodium chloride solution, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by column chromatography (90:10 to 80:20), petroleum ether:ethyl acetate), by means of which methyl (3R, 4S)-3-hydroxy-4-tert-butylsilyloxyundec-5-enoate was obtained as a colorless oil in a yield of 93% (6.97 g, 14.7 mmol).
Reaction SMILES: [OH:1][CH2:2][C@H:3]1[CH2:8][CH2:7][C@H:6]([CH2:9][OH:10])[CH2:5][CH2:4]1.C(N(CC)CC)C.[Si:18](Cl)([C:21]([CH3:24])([CH3:23])[CH3:22])([CH3:20])[CH3:19].C(OCC)(=O)C>CN(C)C=O>[Si:18]([O:1][CH2:2][C@H:3]1[CH2:8][CH2:7][C@H:6]([CH2:9][OH:10])[CH2:5][CH2:4]1)([C:21]([CH3:24])([CH3:23])[CH3:22])([CH3:20])[CH3:19]
Reactant: CC(C)(C)[Si](C)(C)Cl
Reactant: OC[C@H]1CC[C@H](CO)CC1
Solvent: CCOC(C)=O
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: CC(C)(C)[Si](C)(C)OC[C@H]1CC[C@H](CO)CC1

Procedure:
In 250 ml of dry dimethylformamide were dissolved 10.0 g of trans-1,4-dihydroxymethylcyclohexane and 14.5 ml of triethylamine, and a solution of 10.24 g of t-butyldimethylsilyl chloride dissolved in 50 ml of dry dimethylformamide was added dropwise thereto with stirring under ice-cooling, and the resulting mixture was stirred under ice-cooling for 1 hour. To the reaction mixture were added 200 ml of ethyl acetate, the precipitated triethylamine hydrochloride was removed by filtration, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography employing cyclohexane-ethyl acetate (2:1) as an eluting solvent to obtain 11.9 g of the desired compound as a colorless oil.
Reaction SMILES: [C:1]([N:5]1[C:9](=[O:10])[C:8](Cl)=[C:7]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[S:6]1(=[O:19])=[O:18])([CH3:4])([CH3:3])[CH3:2].[CH3:20][O:21][C:22]1[CH:27]=[CH:26][C:25]([NH2:28])=[CH:24][CH:23]=1>CC#N>[C:1]([N:5]1[C:9](=[O:10])[C:8]([NH:28][C:25]2[CH:26]=[CH:27][C:22]([O:21][CH3:20])=[CH:23][CH:24]=2)=[C:7]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[S:6]1(=[O:19])=[O:18])([CH3:4])([CH3:3])[CH3:2]
Reactant: COc1ccc(N)cc1
Reactant: CC(C)(C)N1C(=O)C(Cl)=C(c2ccccc2)S1(=O)=O
Solvent: CC#N
Product: COc1ccc(NC2=C(c3ccccc3)S(=O)(=O)N(C(C)(C)C)C2=O)cc1
Temperature: 140 °C
Yield: 39.3 %

Procedure:
A mixture of 2-tert-butyl-4-chloro-5-phenylisothiazol-3(2H)-one 1,1-dioxide (0.300 g, 1.001 mmol), (4-methoxyphenyl)amine (0.136 g, 1.101 mmol) and TEA (0.140 ml, 1.001 mmol) in MeCN (3 ml) was heated in a microwave reactor at 120° C. for 20 mins, 130° C. for 30 mins, 140° C. for 30 mins and then using an oil bath at 120° C. for 24 h. The mixture was evaporated and the residue was purified by silica gel column chromatography using a 17% EtOAc in petroleum ether 40-60° C. as eluent, to give the title compound (0.152 g, 39%). 1H NMR (500 MHz, CDCl3): δ 7.24-7.14 (m, 1H), 7.12-7.08 (m, 1H), 7.07 (bs, 1H), 6.62 (d, 2H), 6.50 (d, 2H), 3.67 (s, 3H), 1.77 (s, 9H); 13C NMR (125 MHz CDCl3): δ 160.2, 157.2, 131.2, 129.6, 129.4, 128.9, 128.1, 125.1, 123.9, 113.8, 109.9, 61.9, 55.7, 27.9; Mass Spectrum: M+H+ 387.
Reaction SMILES: Cl[C:2]1[C:7]([CH2:8][C:9]([O:11][CH3:12])=[O:10])=[C:6]([N:13]([CH3:15])[CH3:14])[N:5]=[CH:4][N:3]=1.[C:16]([C:20]1[CH:21]=[C:22]([OH:26])[CH:23]=[CH:24][CH:25]=1)([CH3:19])([CH3:18])[CH3:17].C(=O)([O-])[O-].[K+].[K+].C1OCCOCCOCCOCCOCCOC1>CN(C)C=O.C(OCC)C>[C:16]([C:20]1[CH:21]=[C:22]([CH:23]=[CH:24][CH:25]=1)[O:26][C:2]1[C:7]([CH2:8][C:9]([O:11][CH3:12])=[O:10])=[C:6]([N:13]([CH3:15])[CH3:14])[N:5]=[CH:4][N:3]=1)([CH3:19])([CH3:17])[CH3:18]
Reactant: COC(=O)Cc1c(Cl)ncnc1N(C)C
Reactant: CC(C)(C)c1cccc(O)c1
Agent: C1COCCOCCOCCOCCOCCO1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOCC
Solvent: CN(C)C=O
Product: COC(=O)Cc1c(Oc2cccc(C(C)(C)C)c2)ncnc1N(C)C
Yield: 87.4 %

Procedure:
A mixture of methyl 4-chloro-6-dimethylamino-pyrimidin-5-yl-acetate (22.9 g, 100 mmol), 3-tert.butylphenol (15.0 g, 100 mmol), potassium carbonate (20.7 g, 150 mmol) and a catalytic amount of 18-crown-6 is heated in dimethylformamide (50 ml) at +130° C. for 6 hours. The reaction mixture is diluted with diethyl ether, washed with 2 n NaOH and brine, dried (MgSO4) and evaporated to give methyl 4-(3-tert.butylphenoxy)-6-dimethylamino-pyrimidin-5-yl-acetate as a yellow oil (30 g).
Reaction SMILES: C([BH3-])#N.[Na+].[CH2:5]1[N:10]2C3CCNCC=3[C:13]3=[CH:14][CH:15]=[CH:16][C:8](=[C:9]23)[O:7][CH2:6]1.Cl.[OH-].[Na+]>FC(F)(F)C(O)=O>[O:7]1[C:8]2[CH:16]=[CH:15][CH:14]=[CH:13][C:9]=2[N:10]=[CH:5][CH2:6]1
Reactant: c1cc2c3c(c1)c1c(n3CCO2)CCNC1
Agent: Cl
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: O=C(O)C(F)(F)F
Product: C1=Nc2ccccc2OC1

Procedure:
Powdered sodium cyanoborohydride (25 g) is added, in small portions, to a well-stirred and cooled (5°) solution of 1,2,7,8,9,10-hexahydropyrido[3', 4': 4,5]pyrrolo[1,2,3-de][1,4]benzoxazine (20 g) in trifluoroacetic acid (250 ml) at such a rate that excessive frothing is avoided. After the addition is complete, the mixture is stirred at room temperature for 2 hours, treated with 6N hydrochloric acid (150 ml), and refluxed for 30 minutes. It is then cooled and basified with 25% sodium hydroxide and extracted thrice with chloroform. The combined chloroform extracts are washed thoroughly with water, dried over magnesium sulfate, and stripped of the solvent under reduced pressure to furnish a crystalline solid which is recrystallized from hexane to yield the title compound, m.p. 112°-113°.
Reaction SMILES: CC(O)C.Cl.C(OC([NH:13][CH:14]([CH2:27][O:28][C:29]([NH:31][CH3:32])=[O:30])[CH2:15][O:16][C:17]1[C:21]2[CH:22]=[C:23]([Cl:26])[CH:24]=[CH:25][C:20]=2[O:19][N:18]=1)=O)(C)(C)C>CO>[ClH:26].[NH2:13][CH:14]([CH2:27][O:28][C:29]([NH:31][CH3:32])=[O:30])[CH2:15][O:16][C:17]1[C:21]2[CH:22]=[C:23]([Cl:26])[CH:24]=[CH:25][C:20]=2[O:19][N:18]=1
Reactant: CNC(=O)OCC(COc1noc2ccc(Cl)cc12)NC(=O)OC(C)(C)C
Agent: Cl
Solvent: CC(C)O
Solvent: CO
Product: CNC(=O)OCC(N)COc1noc2ccc(Cl)cc12

Procedure:
In 10 ml of methanol is dissolved 3-(2-tert-butoxycarbonylamino-3-methylaminocarbonyloxypropoxy)-5-chloro-1,2-benzoisoxazole, and to this solution is added 9.6 ml of a 2-propanol solution (7.5N) of hydrogen chloride, and they are subjected to reaction at 20°-25° C. for 4.5 hours. The solvent is removed from the reaction mixture by distillation under reduced pressure, and to the residue obtained is added 5 ml of 2-propanol, after which the crystals precipitated are collected by filtration, to obtain 0.30 g of colorless, crystalline 3-(2-amino-3-methylaminocarbonyloxypropoxy)-5-chloro-1,2-benzoisoxazole hydrochloride having a melting point of 206°-209° C.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[S:9]([NH:12][C:13]1[C:18]([CH3:19])=[CH:17][C:16]([CH3:20])=[CH:15][N:14]=1)(=[O:11])=[O:10].[CH3:21][C:22](N=C(N(C)C)N(C)C)([CH3:24])[CH3:23].BrCC(C)C>C(#N)C>[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[S:9]([N:12]([C:13]1[C:18]([CH3:19])=[CH:17][C:16]([CH3:20])=[CH:15][N:14]=1)[CH2:21][CH:22]([CH3:24])[CH3:23])(=[O:10])=[O:11]
Reactant: CN(C)C(=NC(C)(C)C)N(C)C
Reactant: Cc1cnc(NS(=O)(=O)c2ccc(F)cc2Cl)c(C)c1
Solvent: CC#N
Solvent: CC(C)CBr
Product: Cc1cnc(N(CC(C)C)S(=O)(=O)c2ccc(F)cc2Cl)c(C)c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 6.1 %

Procedure:
To a solution of 2-chloro-N-(3,5-dimethylpyridin-2-yl)-4-fluorobenzenesulfonamide (117 mg, 0.372 mmol) in acetonitrile (4 mL) stirred at room temperature, was added N″-(1,1-dimethylethyl)-N,N,N′,N′-tetramethylguanidine (127 mg, 0.743 mmol). The reaction mixture was stirred at room temperature for 1 hour, then 1-bromo-2-methylpropane (0.081 mL, 0.743 mmol) was added. The reaction vessel was sealed and heated under microwaves at 150° C. for 30 minutes. The solvent was evaporated in vacuo and the crude was purified by mass directed autoprep (ammonium carbonate modifier) to give the title compound (8.4 mg). LCMS (2 min, High pH) Rt 1.45 min, m/z (ES+) 371 (M+H).
Reaction SMILES: [CH2:1]([NH2:19])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18].[S:20](N)([NH2:23])(=[O:22])=[O:21]>C1COCC1>[CH2:1]([NH:19][S:20]([NH2:23])(=[O:22])=[O:21])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18]
Reactant: NS(N)(=O)=O
Reactant: CCCCCCCCCCCCCCCCCCN
Solvent: C1CCOC1
Product: CCCCCCCCCCCCCCCCCCNS(N)(=O)=O
Yield: 17.2 %

Procedure:
0.270 g, (1.0 mmol) of N-octadecylamine and 0.100 g (1.0 mmol) of sulfamide in 50 ml of THF (50 mL) are stirred and refluxed for 51 h. The solvent is evaporated and the crude is purified in a chromatography column, using CH2Cl2:MeOH/NH3 9:1 as eluyent. 0.06 g of white solid are obtained. Yield 18%; mp=105-107° C.;
Reaction SMILES: C[O:2][P:3]([O:6][CH3:7])[O:4][CH3:5].Cl[C:9]([O:11][C:12]1[CH:17]=[CH:16][C:15]([Cl:18])=[C:14]([Cl:19])[CH:13]=1)=[O:10]>>[Cl:19][C:14]1[CH:13]=[C:12]([CH:17]=[CH:16][C:15]=1[Cl:18])[O:11][C:9]([P:3](=[O:2])([O:6][CH3:7])[O:4][CH3:5])=[O:10]
Reactant: COP(OC)OC
Reactant: O=C(Cl)Oc1ccc(Cl)c(Cl)c1
Product: COP(=O)(OC)C(=O)Oc1ccc(Cl)c(Cl)c1

Procedure:
From 10.3 g (85 mmole) of trimethylphosphite and 13.5 g (60 mmole) of 3,4-dichlorophenyl chloroformate (100°, 2 hours). Yield 11.4 g (64%) B.p.0.04 164° C. nD20 1.5271. Solidifies to colourless crystals m.p. 58°-9° C.
Reaction SMILES: [OH:1][C:2]1[C:7]([CH2:8][CH2:9][CH3:10])=[C:6]([OH:11])[CH:5]=[CH:4][C:3]=1[C:12](=O)[CH3:13].Cl.[NH2:16][OH:17].C([O-])(=O)C.[Na+].O>CCO>[OH:1][C:2]1[C:7]([CH2:8][CH2:9][CH3:10])=[C:6]([OH:11])[CH:5]=[CH:4][C:3]=1[C:12](=[N:16][OH:17])[CH3:13]
Reactant: NO
Reactant: CCCc1c(O)ccc(C(C)=O)c1O
Agent: CC(=O)[O-]
Agent: Cl
Agent: [Na+]
Solvent: CCO
Solvent: O
Product: CCCc1c(O)ccc(C(C)=NO)c1O
Temperature: 25 °C
Yield: 95.3 %

Procedure:
1-(2,4-dihydroxy-3-propylphenyl)ethanone (1.50 g, 7.72 mmol), hydroxylamine hydrochloride (1.61 g, 23.2 mmol), and anhydrous sodium acetate (1.90 g, 23.2 mmol) were combined in EtOH (30 mL) and stirred under reflux for 15 h. After cooling to rt, water (20 mL) was added, the EtOH was removed under reduced pressure and the aqueous phase was extracted with EtOAc (2×). The combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced pressure to give 1.54 g (95%) of the title compound as a light-green solid. 1H NMR (400 MHz, CDCl3): δ 0.93 (t, 3H), 1.52 (m, 2H), 2.23 (s, 3H), 2.60 (t, 2H), 6.32 (d, 2H), 7.12 (d, 2H).
Reaction SMILES: [CH3:1][NH:2][C:3](=[O:6])[CH:4]=[CH2:5].[CH3:7][O:8][C:9]1[CH:10]=[C:11]([CH:14]=[C:15]([O:17][CH3:18])[CH:16]=1)[CH2:12][NH2:13]>C(O)C>[CH3:18][O:17][C:15]1[CH:14]=[C:11]([CH2:12][NH:13][CH2:5][CH2:4][C:3]([NH:2][CH3:1])=[O:6])[CH:10]=[C:9]([O:8][CH3:7])[CH:16]=1
Reactant: COc1cc(CN)cc(OC)c1
Reactant: C=CC(=O)NC
Solvent: CCO
Product: CNC(=O)CCNCc1cc(OC)cc(OC)c1
Temperature: 140 °C

Procedure:
N-methylacrylamide (ABCR; 500 mg, 5.87 mmol) and 3,5-dimethoxybenzylamine (Aldrich; 0.98 mL, 6.46 mmol) were dissolved in ethanol (4 mL) and heated in a microwave at 140° C. for 45 minutes. The mixture was poured onto a 20 g SCX-2 column, washed with methanol and eluted with 3.5N NH3 in methanol. The product fractions were evaporated to the title compound as a yellow oil (1.3 g, 88%).
Reaction SMILES: [C:1]([O:5][C:6](=[O:12])[NH:7][CH2:8][CH2:9][CH2:10][NH2:11])([CH3:4])([CH3:3])[CH3:2].[N:13]1[C:22]2[C:21](=O)[CH2:20][CH2:19][CH2:18][C:17]=2[CH:16]=[CH:15][CH:14]=1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C(Cl)Cl>[C:1]([O:5][C:6](=[O:12])[NH:7][CH2:8][CH2:9][CH2:10][NH:11][CH:21]1[C:22]2[N:13]=[CH:14][CH:15]=[CH:16][C:17]=2[CH2:18][CH2:19][CH2:20]1)([CH3:4])([CH3:2])[CH3:3]
Reactant: O=C1CCCc2cccnc21
Reactant: CC(C)(C)OC(=O)NCCCN
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: ClCCl
Product: CC(C)(C)OC(=O)NCCCNC1CCCc2cccnc21

Procedure:
Using General Procedure B, reaction of (3-amino-propyl)-carbamic acid tert-butyl ester, 6,7-dihydro-5H-quinolin-8-one and NaBH(OAc)3 in CH2Cl2 gave [3-(5,6,7,8-tetrahydro-quinolin-8-ylamino)-propyl]-carbamic acid tert-butyl ester as a light brown oil plus 15% impurity. 1H NMR (CDCl3) δ 1.43 (s, 9H), 1.77 (m, 4H), 2.00 (m, 2H), 2.80 (m, 4H), 3.24 (m, 2H), 3.74 (t, 1H, J=7.5 Hz), 5.36 (br, 1H(NH)), 7.06 (m, 1H), 7.37 (d, 1H, J=7.5 Hz), 8.39 (d, 1H, J=4.5 Hz).
Reaction SMILES: Br[C:2]1[C:3]([CH3:21])=[CH:4][C:5]2[S:9][CH2:8][CH:7]([C:10]3[CH:15]=[CH:14][C:13]([CH:16]([CH3:18])[CH3:17])=[CH:12][CH:11]=3)[C:6]=2[C:19]=1[CH3:20].[C:22](=[NH:35])([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O>[C:29]1([C:22]([C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)=[N:35][C:2]2[C:3]([CH3:21])=[CH:4][C:5]3[S:9][CH2:8][CH:7]([C:10]4[CH:15]=[CH:14][C:13]([CH:16]([CH3:18])[CH3:17])=[CH:12][CH:11]=4)[C:6]=3[C:19]=2[CH3:20])[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1
Reactant: Cc1cc2c(c(C)c1Br)C(c1ccc(C(C)C)cc1)CS2
Reactant: N=C(c1ccccc1)c1ccccc1
Agent: [Pd]
Agent: CC(C)(C)[O-]
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Solvent: Cc1ccccc1
Solvent: O
Product: Cc1cc2c(c(C)c1N=C(c1ccccc1)c1ccccc1)C(c1ccc(C(C)C)cc1)CS2
Reaction time: 0.25 h

Procedure:
To a solution of 5-bromo-3-(4-isopropylphenyl)-4,6-dimethyl-2,3-dihydro-1-benzothiophene obtained in Reference Example 259 (870 mg, 2.41 mmol) and benzophenone imine (0.76 mL, 2.89 mmol) in toluene (15 mL) were added tris(dibenzylideneacetone)dipalladium (22 mg, 0.024 mmol) and BINAP (45 mg, 0.072 mmol) at room temperature, and the mixture was stirred under argon atmosphere for 15 minutes. To the reaction solution was added sodium tert-butoxide (324 mg, 3.37 mmol) at room temperature, and the mixture was heated under reflux under argon stream for 16 hours. Water was added to the reaction solution, which was extracted with ethyl acetate, and the organic layer was washed with water and a saturated brine, was dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure to obtain the crude product of N-(diphenylmethylene)-3-(4-isopropylphenyl)-4,6-dimethyl-2,3-dihydro-1-benzothien-5-amine. This compound was dissolved in THF (10 mL), to which 1 N hydrochloric acid (2 mL) was added, and the mixture then was heated under reflux for 30 minutes. The solvent was concentrated under reduced pressure to obtain the residue, which was neutralized with 1 N aqueous sodium hydroxide solution. The product was extracted with ethyl acetate. The combined extract was washed with water, dried over magnesium sulfate, and then concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:10) to obtain 521 mg (yield 73%) of the title compound. Melting point: 121-122° C. (hexane-ethyl acetate).