Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [BH4-].[Na+].[CH2:3]([S:5][CH:6]([S:25][CH2:26][CH3:27])[C@@H:7]([C@H:9]([C@H:11]([CH:13](S(C1C=CC(C)=CC=1)(=O)=O)O)[OH:12])[OH:10])[OH:8])[CH3:4]>CS(C)=O>[CH2:26]([S:25][CH:6]([S:5][CH2:3][CH3:4])[C@@H:7]([C@H:9]([C@H:11]([CH3:13])[OH:12])[OH:10])[OH:8])[CH3:27]
Reactant: CCSC(SCC)[C@H](O)[C@@H](O)[C@@H](O)C(O)S(=O)(=O)c1ccc(C)cc1
Agent: [BH4-]
Agent: [Na+]
Solvent: CS(C)=O
Product: CCSC(SCC)[C@H](O)[C@@H](O)[C@H](C)O
Temperature: 90 °C

Procedure:
A 1000 ml round flask was charged with 4 g (105 mmoles) of NaBH4, and thereto 100 ml of DMSO was added. The mixture was stirred by magnetic stirrer until the mixture became an almost clear solution. To the solution there was slowly added 100 ml of DMSO containing 20 g (49 mmoles) of 5-tosyl-L-(+)-arabinose-diethylmercaptal for about 2 hours with stirring. After addition, the mixture was further stirred for half an hour at room temperature. Then, the mixture was heated on a water bath for one hour at 90° C with occasional stirring. After the mixture was evaporated to dryness on a water bath of 90° C. under vacuum (1 Torr), the mixture was cooled and the obtained residue was decomposed with ice water. A small amount of scum was filtered off and the obtained clear filtrate (pH>13) was made slightly acidic with 5% acetic acid. After the filtrate was thoroughly extracted with ether, the ether layer was dried with sodium sulfate and the solvent was evaporated from the ether layer to give 9.5 g of 5-deoxy-L-(+)-arabinose-diethylmercaptal as a white solid residue (yield: 81%).
Reaction SMILES: [C:1]([O:7][CH2:8][CH3:9])(=[O:6])[CH2:2][C:3]([CH3:5])=[O:4].[OH-].[Na+].[C:12]1([CH3:21])[CH:17]=C[CH:15]=[C:14](C(Cl)=O)[CH:13]=1.[Na].C1(C)C=CC=C(C(CC(=O)CC(OCC)=O)=O)C=1.[Cl-].[NH4+]>O.C1C=CC=CC=1>[C:12]1([CH3:21])[CH:13]=[CH:14][CH:15]=[C:5]([C:3]([CH2:2][C:1]([O:7][CH2:8][CH3:9])=[O:6])=[O:4])[CH:17]=1
Reactant: CCOC(=O)CC(C)=O
Reactant: Cc1cccc(C(=O)Cl)c1
Agent: CCOC(=O)CC(=O)CC(=O)c1cccc(C)c1
Agent: [Cl-]
Agent: [NH4+]
Solvent: O
Solvent: c1ccccc1
Product: CCOC(=O)CC(=O)c1cccc(C)c1
Yield: 17.5 %

Procedure:
To a cold (5° C.) mixture of 137.5 g (1.05 mole) of ethyl acetoacetate, 175 ml. of benzene, 325 ml. of water, and 45.8 ml. of 33% sodium hydroxide was added simultaneously 221.05 g (1.430 mole) of m-toluoyl chloride and 190 ml. of 33% sodium hydroxide as described in Example 4. The aqueous solution of sodium salt of ethyl m-toluoylacetoacetate was stirred with 56.3 g of ammonium chloride overnight and worked up as described in Example 4 to give 38.0 g (17%) of crude ethyl m-toluoylacetate after a Kugelrohr distillation (95°-98° C. at 0.05 mm Hg). A mixture of 20.6 g (0.1 mole) of crude ethyl m-toluoylacetate, 13.6 g (0.105 mole) of sulfuryl chloride, and 30 ml. of chloroform was held at reflux for 6 hours and worked up as described in Example 4 to give 25.0 g of ethyl 2-chloro-m-toluoylacetate, which was used directly as described below. A mixture of 22.5 g (0.1 mole) of ethyl 2-chloro-m-toluoylacetate, 7.6 g (0.1 mole) of thiourea and 100 ml. of ethanal was held at reflux for 2 hours and worked up as described in Example 4 to give 23.0 g of solid, which was recrystallized from ethanol to give 11.6 g (44%) of ethyl 2-amino-4-(m-tolyl)-5-thiazolecarboxylate, m.p. 185°-187° C. An additional 4.5 g (17%) of less pure ethyl 2-amino-4-(m-tolyl)-5-thiazolecarboxylate, m.p. 183°-184° C. was obtained by concentration of the mother liquor. To a cold (-5° C.) mixture of 10.5 g (0.04 mole) of ethyl 2-amino-4-(m-tolyl)-5-thiazolecarb and 80 ml. of 85% phosphoric acid was added 40 ml. of 70% nitric acid. To the vigorously stirred above mixture was added 3.0 g (0.0434 mole) of sodium nitrite in 20 minutes. The reaction mixture was stirred for 10 minutes and poured into a mixture of 4.0 g (0.04 mole) of cuprous chloride, 20 ml. of concentrated hydrochloric acid and 20 ml. of water. After the gas evolution had subsided the reaction mixture was extracted with ether, dried (MgSO4) and concentrated under reduced pressure to give 10 g of oil which was Kugelrohr distilled (135°-140° C. at 0.05 mm) to give 6.5 g of oil, which was crystallized from ethanol to give 3.9 g (34%) of the desired product as a white solid, m.p. 41°-42° C.
Reaction SMILES: C(OC([N:8]1[C:16]2[C:11](=[CH:12][C:13]([NH:17][C:18]([NH:20][CH2:21][CH2:22][C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([O:29][CH3:30])[CH:24]=3)=[O:19])=[CH:14][CH:15]=2)[C:10]([NH2:31])=[N:9]1)=O)(C)(C)C>Cl.O1CCOCC1>[NH2:31][C:10]1[C:11]2[C:16](=[CH:15][CH:14]=[C:13]([NH:17][C:18]([NH:20][CH2:21][CH2:22][C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([O:29][CH3:30])[CH:24]=3)=[O:19])[CH:12]=2)[NH:8][N:9]=1
Reactant: COc1cccc(CCNC(=O)Nc2ccc3c(c2)c(N)nn3C(=O)OC(C)(C)C)c1
Agent: Cl
Solvent: C1COCCO1
Product: COc1cccc(CCNC(=O)Nc2ccc3[nH]nc(N)c3c2)c1

Procedure:
6.2 700 mg of tert-butyl-3-amino-5-{3-[2-(3-methoxyphenyl)ethyl]-ureido}indazole-1-carboxylate (1.6 mmol) are stirred for 16 hours with 10 ml of HCl/dioxane (4 M). The batch is concentrated and evaporated three times with 10 ml of toluene each time in a rotary evaporator. The residue is purified by column chromatography on silica gel (eluent: dichloromethane:methanol 9:1). Drying gives 120 mg of “A20” (22%), MS-FAB (M+H+)=326,
Reaction SMILES: [Cl:1][C:2]1[CH:12]=[C:11]([C:13]([F:16])([F:15])[F:14])[CH:10]=[CH:9][C:3]=1[O:4][CH2:5][C:6]([OH:8])=O.[Cl:17][C:18]1[CH:19]=[C:20]([NH2:30])[CH:21]=[CH:22][C:23]=1[CH2:24][N:25]1[CH2:29][CH2:28][CH2:27][CH2:26]1>>[Cl:17][C:18]1[CH:19]=[C:20]([NH:30][C:6](=[O:8])[CH2:5][O:4][C:3]2[CH:9]=[CH:10][C:11]([C:13]([F:16])([F:15])[F:14])=[CH:12][C:2]=2[Cl:1])[CH:21]=[CH:22][C:23]=1[CH2:24][N:25]1[CH2:26][CH2:27][CH2:28][CH2:29]1
Reactant: O=C(O)COc1ccc(C(F)(F)F)cc1Cl
Reactant: Nc1ccc(CN2CCCC2)c(Cl)c1
Product: O=C(COc1ccc(C(F)(F)F)cc1Cl)Nc1ccc(CN2CCCC2)c(Cl)c1

Procedure:
The product was prepared according to general working method I from (2-chloro-4-trifluoromethyl-phenoxy)-acetic acid (Z2b) and 3-chloro-4-pyrrolidin-1-ylmethyl-phenylamine (140b).
Reaction SMILES: [CH:1]12[O:7][CH:6]1[CH2:5][CH2:4][N:3]([C:8]([O:10][CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)=[O:9])[CH2:2]2.[N-:18]=[N+:19]=[N-:20].[Na+].[Cl-].[NH4+]>CO.O>[N:18]([C@H:1]1[C@H:6]([OH:7])[CH2:5][CH2:4][N:3]([C:8]([O:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[O:9])[CH2:2]1)=[N+:19]=[N-:20]
Reactant: O=C(OCc1ccccc1)N1CCC2OC2C1
Reactant: [N-]=[N+]=[N-]
Agent: [Cl-]
Agent: [NH4+]
Agent: [Na+]
Solvent: O
Solvent: CO
Product: [N-]=[N+]=N[C@@H]1CN(C(=O)OCc2ccccc2)CC[C@H]1O
Temperature: 65 °C
Yield: 100.4 %

Procedure:
Benzyl 7-oxa-3-azabicyclo[4.1.0]heptane-3-carboxylate (6.78 g, 29.1 mmol), sodium azide (3.78 g, 2 equiv), and ammonium chloride (1.56 g, 1 equiv) were dissolved in methanol (100 mL) and water (20 mL). The mixture was heated at 65° C. for 18 h. The mixture was cooled to rt and methanol was removed under vacuum. The aqueous residue was extracted with ether (3×120 mL). The combined ether layers were washed with brine (30 mL) and dried over Na2SO4. Concentration afforded (3R,4R)-benzyl 3-azido-4-hydroxypiperidine-1-carboxylate (8.07 g, quant.) which was used for without further purification. LC-MS (3 min) tR=1.45 min., m/z 277 (M+1).
Reaction SMILES: Cl[C:2]1[N:3]=[C:4]([N:21]2[CH2:26][CH2:25][O:24][CH2:23][CH2:22]2)[C:5]2[S:10][C:9]([CH2:11][N:12]3[CH2:17][CH2:16][CH:15]([N:18]([CH3:20])[CH3:19])[CH2:14][CH2:13]3)=[CH:8][C:6]=2[N:7]=1.C([N:34]1[C:42]2[C:37](=[CH:38][CH:39]=[CH:40][CH:41]=2)[C:36](B(O)O)=[CH:35]1)(OC(C)(C)C)=O.C(=O)([O-])[O-].[Na+].[Na+]>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].C(#N)C>[NH:34]1[C:42]2[C:37](=[CH:38][CH:39]=[CH:40][CH:41]=2)[C:36]([C:2]2[N:3]=[C:4]([N:21]3[CH2:26][CH2:25][O:24][CH2:23][CH2:22]3)[C:5]3[S:10][C:9]([CH2:11][N:12]4[CH2:17][CH2:16][CH:15]([N:18]([CH3:20])[CH3:19])[CH2:14][CH2:13]4)=[CH:8][C:6]=3[N:7]=2)=[CH:35]1
Reactant: CC(C)(C)OC(=O)n1cc(B(O)O)c2ccccc21
Reactant: CN(C)C1CCN(Cc2cc3nc(Cl)nc(N4CCOCC4)c3s2)CC1
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: O=C([O-])[O-]
Solvent: CC#N
Product: CN(C)C1CCN(Cc2cc3nc(-c4c[nH]c5ccccc45)nc(N4CCOCC4)c3s2)CC1
Temperature: 140 °C
Yield: 26.8 %

Procedure:
A microwave vessel was charged with [1-(2-chloro-4-morpholin-4-yl-thieno[3,2-d]pyrimidin-6-ylmethyl)-piperidin-4-yl]-dimethyl-amine (0.500 g, 1.26 mmol), 1-BOC-indole-3-yl-boronic acid (363 mg, 1.39 mmol), 1 N sodium carbonate solution (3 mL), acetonitrile (9 mL) and Pd(dppf)Cl2 (103 mg. 0.126 mmol), then the mixture was degassed, sealed, and heated at 140° C. under microwave irradiation for 20 min. The reaction mixture was diluted with dichloromethane (100 mL) and 1 N sodium carbonate solution (10 mL) then the phases were separated. The organic phase was washed with saturated aqueous sodium bicarbonate solution (15 mL) then dried (MgSO4) and concentrated in vacuo. Purification by chromatography (silica, 0 to 15% of a 9.5:0.5 MeOH:NH4OH solution in dichloromethane) followed by trituration with hot ethanol afforded 101 (161 mg, 27%) as a cream powder. MS m/e 477 [M+H]+. 1H NMR (400 MHz, CHCl3-d) δ ppm 1.53-1.68 (m, 2H) 1.75 (br. s., 1H) 1.83 (d, J=11.6 Hz, 2H) 2.05-2.22 (m, 3H) 2.30 (s, 6H) 3.04 (d, J=12.1 Hz, 2H) 3.81 (s, 2H) 3.88-3.99 (m, 4H) 4.01-4.13 (m, 4H) 7.21-7.32 (m, 2H) 7.37-7.45 (m, 1H) 8.14 (d, J=2.5 Hz, 1H) 8.64-8.70 (m, 1H) 8.76 (br. s., 1H)
Reaction SMILES: [NH2:1][C:2]1[N:10]=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.C(P(=O)(OCC)OCC)#N.C(N(CC)CC)C.[CH3:28][O:29][C:30]1[CH:37]=[CH:36][C:33]([CH2:34][NH2:35])=[CH:32][CH:31]=1>CN(C)C=O>[NH2:1][C:2]1[N:10]=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([NH:35][CH2:34][C:33]1[CH:36]=[CH:37][C:30]([O:29][CH3:28])=[CH:31][CH:32]=1)=[O:6]
Reactant: Nc1ncccc1C(=O)O
Reactant: COc1ccc(CN)cc1
Agent: CCOP(=O)(C#N)OCC
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: COc1ccc(CNC(=O)c2cccnc2N)cc1
Yield: 100 %

Procedure:
2-Aminonicotinic acid (7.15 g) was suspended in N,N-dimethylformamide (100 ml) and 4-methoxybenzylamine (8.12 ml), diethyl cyanophosphonate (9.92 ml) and triethylamine (8.66 ml) were added sequentially with stirring and cooling on ice. The reaction mixture was stirred at room temperature for 15.5 hours, concentrated under reduced pressure, and extracted with ethyl acetate. The extract was washed with water, dried (Na2SO4) and then the solvent was distilled off under reduced pressure to give the title compound (15.9 g, about 100%). Recrystallization from ethyl acetate-ethyl ether yielded a colorless crystal, melting point 165 to 166° C.
Reaction SMILES: O[C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[C:4]([CH3:9])[C:3]=1[CH2:10][CH2:11][CH2:12][C:13]([CH3:16])([OH:15])[CH3:14].C1(C)C=CC(S(O)(=O)=O)=CC=1.O>C1C=CC=CC=1>[CH3:14][C:13]1([CH3:16])[CH2:12][CH2:11][CH2:10][C:3]2[C:4]([CH3:9])=[CH:5][C:6]([CH3:8])=[CH:7][C:2]=2[O:15]1
Reactant: Cc1cc(C)c(CCCC(C)(C)O)c(O)c1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: c1ccccc1
Solvent: O
Product: Cc1cc(C)c2c(c1)OC(C)(C)CCC2
Yield: 97.9 %

Procedure:
A solution of the diol (D) (100 mg, 0.45 mM) and p-toluenesulphonic acid (10 mg) in benzene (20 ml) was heated for 1 hour under reflux in an apparatus for the azeotropic removal of water. The reaction solution was cooled, and washed with aqueous sodium hydroxide (2M), followed by brine. The dried (Na2SO4) solution was concentrated in vacuo. The residual oil was purified by flash chromatography, eluting with toluene/hexane (1:1 v/v), to give 2,3,4,5-tetrahydro-2,2,6,8-tetramethyl-1-benzoxepin (E) as a colourless oil (90 mg, 98% yield); NMR: 1.25(6H,s), 1.63(4H,m), 2.23(3H,s), 2.25(3H,s), 2.73(2H,m), 6.57(1H,s), 6.69(1H,s).
Reaction SMILES: [Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[CH:4][C:3]=1[S:12]([CH2:15][CH2:16][NH:17][CH2:18][C:19]1O[CH:21]=[CH:22][CH:23]=1)(=[O:14])=[O:13].ClC1C2C(=CC=CC=2)C=CC=1SC[CH2:37][NH:38]CC1C=CC=CN=1>>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[CH:4][C:3]=1[S:12]([CH2:15][CH2:16][NH:17][CH2:18][C:19]1[CH:23]=[CH:22][CH:21]=[CH:37][N:38]=1)(=[O:14])=[O:13]
Reactant: O=S(=O)(CCNCc1ccco1)c1ccc2ccccc2c1Cl
Reactant: Clc1c(SCCNCc2ccccn2)ccc2ccccc12
Product: O=S(=O)(CCNCc1ccccn1)c1ccc2ccccc2c1Cl
Yield: 78 %

Procedure:
Prepared as described for compound 25 from 2-[(1-chloronaphthalen-2-yl)sulfanyl]-N-(pyridin-2-ylmethyl)ethanamine in 78% yield as yellow oil.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([C:9]#[C:10][CH:11]=[C:12]2[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]2)[CH:5]=[C:6]([F:8])[CH:7]=1.Cl[C:19]1[C:24]([N+:25]([O-:27])=[O:26])=[CH:23][CH:22]=[C:21]([O:28][CH3:29])[N:20]=1.C(=O)([O-])[O-].[K+].[K+].O>CN(C)C(=O)C>[F:1][C:2]1[CH:3]=[C:4]([C:9]#[C:10][CH:11]=[C:12]2[CH2:13][CH2:14][N:15]([C:19]3[C:24]([N+:25]([O-:27])=[O:26])=[CH:23][CH:22]=[C:21]([O:28][CH3:29])[N:20]=3)[CH2:16][CH2:17]2)[CH:5]=[C:6]([F:8])[CH:7]=1
Reactant: Fc1cc(F)cc(C#CC=C2CCNCC2)c1
Reactant: COc1ccc([N+](=O)[O-])c(Cl)n1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(=O)N(C)C
Solvent: O
Product: COc1ccc([N+](=O)[O-])c(N2CCC(=CC#Cc3cc(F)cc(F)c3)CC2)n1
Yield: 83.6 %

Procedure:
A solution of Compound 228b (0.046 mg, 0.197 mmol), 2-chloro-6-methoxy-3-nitropyridine (34.6 mg, 0.18 mmol), potassium carbonate (50.3 mg, 0.36 mmol) in N,N-dimethylacetamide was heated in a microwave oven at 165° C. for 3 min. Afterwards, the reaction mixture was cooled, poured into water and extracted with EtOAc. The combined organic layers were washed with brine, dried on Na2SO4 and evaporated to dryness in vacuo to afford a residue, which was purified by flash chromatography (EtOAc—Petroleum Ether 5:95) affording the title product (0.058 g).
Reaction SMILES: Cl[CH2:2][CH:3]1[CH2:8][N:7]([CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH2:6][CH2:5][N:4]1[CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.[C:23]1(=[O:33])[NH:27][C:26](=[O:28])[C:25]2=[CH:29][CH:30]=[CH:31][CH:32]=[C:24]12.[K].C(OCC)(=O)C>CN(C)C=O.C(OC(C)C)(C)C>[C:23]1(=[O:33])[N:27]([CH2:2][CH:3]2[CH2:8][N:7]([CH2:9][C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=3)[CH2:6][CH2:5][N:4]2[CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:26](=[O:28])[C:25]2=[CH:29][CH:30]=[CH:31][CH:32]=[C:24]12
Reactant: ClCC1CN(Cc2ccccc2)CCN1Cc1ccccc1
Reactant: O=C1NC(=O)c2ccccc21
Agent: [K]
Solvent: CC(C)OC(C)C
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: O=C1c2ccccc2C(=O)N1CC1CN(Cc2ccccc2)CCN1Cc1ccccc1
Temperature: 110 °C
Reaction time: 2 h
Yield: 32.9 %

Procedure:
A suspension of 15 g (47.6 mmol) of 2-chloromethyl-1,4-diphenylmethyl piperazine and 8.81 g (47.6 mmol) of potassium phtalimide in 7 ml anhydrous dimethyl formamide was stirred 2 hours at 110° C. After cooling the reaction mixture was taken up with 100 ml ethyl acetate. The mineral salts were filtered off. The solvent was removed, the residue was dissolved in 150 ml ethyl acetate, washed three times with water, dried over magnesium sulfate to give a srystalline product which was resrystallized in isopropyl ether to yield 6.67 g (33%) of title compound. M.P. 124° C.
Reaction SMILES: CN1C=C(CN(C)C(C2N(C3C=CC(F)=CC=3)C(S)=NC=2)=O)C(C)=N1.[F:26][C:27]1[CH:32]=[CH:31][C:30]([N:33]2[C:37]([C:38]([O:40]CC)=[O:39])=[CH:36][N:35]=[C:34]2[S:43][C:44]([C:47]2[C:52]([F:53])=[CH:51][CH:50]=[C:49]([F:54])[C:48]=2[F:55])([CH3:46])[CH3:45])=[CH:29][CH:28]=1.[OH-].[Li+].C1COCC1>O.CO>[F:26][C:27]1[CH:32]=[CH:31][C:30]([N:33]2[C:37]([C:38]([OH:40])=[O:39])=[CH:36][N:35]=[C:34]2[S:43][C:44]([C:47]2[C:52]([F:53])=[CH:51][CH:50]=[C:49]([F:54])[C:48]=2[F:55])([CH3:46])[CH3:45])=[CH:29][CH:28]=1
Reactant: CCOC(=O)c1cnc(SC(C)(C)c2c(F)ccc(F)c2F)n1-c1ccc(F)cc1
Agent: Cc1nn(C)cc1CN(C)C(=O)c1cnc(S)n1-c1ccc(F)cc1
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: CO
Solvent: C1CCOC1
Product: CC(C)(Sc1ncc(C(=O)O)n1-c1ccc(F)cc1)c1c(F)ccc(F)c1F

Procedure:
1-(4-Fluorophenyl)-2-((2-(2,3,6-trifluorophenyl)propan-2-yl)thio)-1H-imidazole-5-carboxylic acid (76) was prepared in a similar manner as that described for the synthesis of compound 7 using ethyl 1-(4-fluorophenyl)-2-((2-(2,3,6-trifluorophenyl)propaN-2-yl)thio)-1H-imidazole-5-carboxylate (75) (0.14 g, 3.5 mmol), lithium hydroxide (15 mg, 0.64 mmol), THF (5 mL), methanol (3 mL), and water (2 mL).
Reaction SMILES: [NH2:1][C:2]1[C:7]2[N:8]=[C:9]([CH2:31][CH2:32][CH3:33])[N:10]([CH2:11][CH2:12][CH2:13][CH2:14][N:15]([O:23]C(OC(C)(C)C)=O)C(=O)OC(C)(C)C)[C:6]=2[C:5]([CH3:34])=[C:4]([CH3:35])[N:3]=1.Cl.O1CCOCC1>ClCCl>[NH2:1][C:2]1[C:7]2[N:8]=[C:9]([CH2:31][CH2:32][CH3:33])[N:10]([CH2:11][CH2:12][CH2:13][CH2:14][NH:15][OH:23])[C:6]=2[C:5]([CH3:34])=[C:4]([CH3:35])[N:3]=1
Reactant: CCCc1nc2c(N)nc(C)c(C)c2n1CCCCN(OC(=O)OC(C)(C)C)C(=O)OC(C)(C)C
Agent: Cl
Solvent: C1COCCO1
Solvent: ClCCl
Product: CCCc1nc2c(N)nc(C)c(C)c2n1CCCCNO
Reaction time: 2 h

Procedure:
The preparation of tert-butyl 4-(4-amino-6,7-dimethyl-2-propyl-1H-imidazo[4,5-c]pyridin-1-yl)butyl[(tert-butoxycarbonyl)oxy]carbamate is described in Parts A-F of Example 14. A mixture of 4M hydrochloric acid in dioxane (2.25 mL, 9.0 mmol, 20 eq) was added to a solution of tert-butyl 4-(4-amino-6,7-dimethyl-2-propyl-1H-imidazo[4,5-c]pyridin-1-yl)butyl[(tert-butoxycarbonyl)oxy]carbamate (0.22 g, 0.45 mmol, 1 eq) in dichloromethane (5 mL) and stirred for 2 hours. The reaction mixture was concentrated under reduced pressure and the resulting white solid was concentrated from chloroform and dried under vacuum to provide N-[4-(4-amino-6,7-dimethyl-2-propyl-1H-imidazo[4,5-c]pyridin-1-yl)butyl]hydroxylamine.
Reaction SMILES: [OH:1][CH:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]([OH:12])[CH2:4][CH2:3]1.[CH3:13][O:14]C(Cl)Cl.Cl>ClCCl.[Ti](Cl)(Cl)(Cl)Cl>[OH:1][CH:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]([OH:12])[CH2:4][CH:3]1[CH:13]=[O:14]
Reactant: COC(Cl)Cl
Reactant: OC1CCC(O)c2ccccc21
Agent: Cl[Ti](Cl)(Cl)Cl
Agent: Cl
Solvent: ClCCl
Product: O=CC1CC(O)c2ccccc2C1O
Yield: 60 %

Procedure:
To a solution of 1,4-dihydroxytetralin (1.640 g, 10 mM), in dichloromethane (50 ml) was added titanium tetrachloride (5.69 g, 30 mM). Then 1,1-dichlorodimethyl ether (1.73 g, 15 mM) was added dropwise under vigorous stirring and the reaction mixture stirred for another 3 h at room temperature. Finally 5% hydrochloric acid (10 ml) was added under ice-cooling. The organic phase was separated and the residual aqueous phase repeatedly extracted with ether. The combined organic phases are washed with saturated saline solution, dried over sodium sulfate and evaporated under vacuum. The residue was crystallized from benzene or alternatively submitted to flash chromatography on silica gel with benzene ethylacetate 85:15, to afford pure title compound in about 60% yield (1.080 g), m.p. 145° C.
Reaction SMILES: CC(O)C.[Na].[N:6]12[CH2:13][CH2:12][CH:9]([CH2:10][CH2:11]1)[C@@H:8]([OH:14])[CH2:7]2.CC([O:18][C:19]([N:21]1[CH2:30][CH2:29][C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[C@@H:22]1[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)=O)C>CC(C)[O-].[Na+].CN(C=O)C.C1(C)C=CC=CC=1>[CH:34]1[CH:35]=[CH:36][C:31]([C@@H:22]2[N:21]([C:19]([O:14][C@@H:8]3[CH:9]4[CH2:12][CH2:13][N:6]([CH2:11][CH2:10]4)[CH2:7]3)=[O:18])[CH2:30][CH2:29][C:28]3[CH:27]=[CH:26][CH:25]=[CH:24][C:23]2=3)=[CH:32][CH:33]=1
Reactant: O[C@H]1CN2CCC1CC2
Reactant: CC(C)OC(=O)N1CCc2ccccc2[C@@H]1c1ccccc1
Agent: CC(C)[O-]
Agent: [Na+]
Agent: [Na]
Solvent: CN(C)C=O
Solvent: Cc1ccccc1
Solvent: CC(C)O
Product: O=C(O[C@H]1CN2CCC1CC2)N1CCc2ccccc2[C@@H]1c1ccccc1
Yield: 64.7 %

Procedure:
In a mixture of sodium isopropoxide prepared from 0.20 g of 2-propanol and 0.08 g of metallic sodium with 20 ml of toluene and 2.5 ml of DMF, 2.58 g of (R)-quinuclidin-3-ol was allowed to react with 5.00 g of (S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline-2-carboxylic acid propan-2-yl ester for 8 hours while evaporating the solvent, thereby obtaining 3.97 g of a solifenacin-containing composition.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([CH3:23])([CH3:22])[C:10](=[O:21])[C:11]([N:16]2[CH:20]=[N:19][CH:18]=[N:17]2)=[CH:12]N(C)C)=[CH:4][CH:3]=1.[CH2:24]([Mg]Br)[CH2:25][CH3:26].Cl>CCOCC>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][C:9]([CH3:22])([CH3:23])[C:10](=[O:21])[C:11]([N:16]2[CH:20]=[N:19][CH:18]=[N:17]2)=[CH:12][CH2:24][CH2:25][CH3:26])=[CH:6][CH:7]=1
Reactant: CCC[Mg]Br
Reactant: CN(C)C=C(C(=O)C(C)(C)Cc1ccc(Cl)cc1)n1cncn1
Agent: Cl
Solvent: CCOCC
Product: CCCC=C(C(=O)C(C)(C)Cc1ccc(Cl)cc1)n1cncn1
Reaction time: 1.5 h
Yield: 60.5 %

Procedure:
49.9 g (0.15 mol) of 1-(4-chlorophenyl)-2,2-dimethyl-5-dimethylamino-4-(1,2,4-triazol-1-yl)-4-penten-3-one are dissolved in 750 ml of ether, and a solution of 33.9 g (0.23 mol) of n-propyl-magnesium bromide in 100 ml of ether is added dropwise at -20° C. The reaction mixture is subsequently stirred for 1.5 hours, during which it warms to room temperature. The reaction mixture is adjusted to a pH value of 7 to 8 with dilute hydrochloric acid. The organic phase is then separated off, washed with water, dried over sodium sulphate and concentrated. The residue is purified by column chromatography (silica gel; ethyl acetate/cyclohexane=3:1). 30.1 g (60.5% of theory) of 1-(4-chlorophenyl)-2,2-dimethyl-4-(1,2,4-triazol-1-yl)-4-octen-3-one of refractive index nD20 1.5429 are obtained.
Reaction SMILES: [O:1]1[CH2:6][CH2:5][C:4](=[O:7])[CH2:3][CH2:2]1.[Br-].[Mg+2].[CH2:10]=[CH2:11].[Br-]>O1CCCC1.CO>[C:10]([C:4]1([OH:7])[CH2:5][CH2:6][O:1][CH2:2][CH2:3]1)#[CH:11]
Reactant: C=C
Reactant: O=C1CCOCC1
Agent: [Br-]
Agent: [Mg+2]
Solvent: CO
Solvent: C1CCOC1
Product: C#CC1(O)CCOCC1
Temperature: 25 °C
Reaction time: 4 h
Yield: 95.2 %

Procedure:
A solution of tetrahydro-4H-pyran-4-one (1.25 g, 12.5 mmol) in tetrahydrofuran (10 mL) was cooled to 0° C. and then treated with a 0.5M solution of ethylene magnesium bromide in tetrahydrofuran (40 mL, 20 mmol). The mixture was stirred at 0° C. for 2 h and at 25° C. for 4 h. The resulting mixture was cooled to 0° C. and then diluted with methanol (10 ml). The solvents were concentrated in vacuo, and the residue was extracted with a saturated aqueous ammonium chloride solution and ethyl acetate. The organic layer was washed with a saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was dried in vacuo to afford solid 4-ethynyl-tetrahydro-pyran-4-ol (1.2 g, 95.2%).
Reaction SMILES: Cl[C:2]([N:4]1[C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=2[C:8](=[O:15])[NH:7][C:6]2[CH:16]=[CH:17][CH:18]=[N:19][C:5]1=2)=[O:3].[CH2:20]([N:22]([CH2:33][CH3:34])[CH2:23][CH2:24][CH2:25][CH2:26][CH:27]1[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]1)[CH3:21]>>[CH2:33]([N:22]([CH2:20][CH3:21])[CH2:23][CH2:24][CH2:25][CH2:26][CH:27]1[CH2:28][CH2:29][N:30]([C:2]([N:4]2[C:10]3[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=3[C:8](=[O:15])[NH:7][C:6]3[CH:16]=[CH:17][CH:18]=[N:19][C:5]2=3)=[O:3])[CH2:31][CH2:32]1)[CH3:34]
Reactant: CCN(CC)CCCCC1CCNCC1
Reactant: O=C1Nc2cccnc2N(C(=O)Cl)c2ccccc21
Product: CCN(CC)CCCCC1CCN(C(=O)N2c3ccccc3C(=O)Nc3cccnc32)CC1
Yield: 62 %

Procedure:
Prepared analogously to Example 4 from 11-(chlorocarbonyl)-5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepin-6-one and 4-[4-(diethylamino)butyl]piperidine in a yield of 62% of theory. Colourless crystals, m.p. 126°-127° C.