Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([NH:8][C:9]1[C:14]([N+:15]([O-])=[O:16])=[CH:13][C:12]([Cl:18])=[C:11]([C:19]([F:22])([F:21])[F:20])[CH:10]=1)([C:3](OCC)=[O:4])=[O:2].Cl>CN(C)C=O.[Pt]>[Cl:18][C:12]1[CH:13]=[C:14]2[C:9]([NH:8][C:1](=[O:2])[C:3](=[O:4])[N:15]2[OH:16])=[CH:10][C:11]=1[C:19]([F:22])([F:21])[F:20]
Reactant: CCOC(=O)C(=O)Nc1cc(C(F)(F)F)c(Cl)cc1[N+](=O)[O-]
Agent: [Pt]
Agent: Cl
Solvent: CN(C)C=O
Product: O=c1[nH]c2cc(C(F)(F)F)c(Cl)cc2n(O)c1=O

Procedure:
A solution of 2.0 g (5.9 mmol) N-ethoxalyl-4-chloro-6-nitro-3-trifluoromethylaniline in 50 ml dimethylformamide was hydrogenated at atm. pressure by using 200 mg 5% Pt-C as a catalyst. The reaction mixture was stirred with 4N hydrochloric acid and the crude product was filtered off. The crude product was dissolved in 25 ml 1N potassium hydroxide and the solution was acidified with concentrated hydrochloric acid. The precipitate was filtered off to give 310 mg 19%) of 7-chloro-1-hydroxy-6-trifluoromethylquinoxaline-2,3(1H,4H)-dione. M.p. decomp. MS (m/e): 280, 1H-NMR (DMSO-d6): 12.2 (1H, broad s), 7.6 (2H, m).
Reaction SMILES: [O:1]=[C:2]([N:7]1[CH2:10][CH2:9][C@H:8]1[C:11]1[N:15]([CH2:16][CH2:17][CH2:18][C:19]2[CH:20]=[N:21][CH:22]=[CH:23][CH:24]=2)[N:14]=[N:13][N:12]=1)[C:3](=[O:6])OC.[CH3:25][C:26]([Mg]Cl)([CH3:29])[CH2:27][CH3:28].[Cl-].[NH4+].CO>O1CCCC1.ClCCl>[O:1]=[C:2]([N:7]1[CH2:10][CH2:9][C@H:8]1[C:11]1[N:15]([CH2:16][CH2:17][CH2:18][C:19]2[CH:20]=[N:21][CH:22]=[CH:23][CH:24]=2)[N:14]=[N:13][N:12]=1)[C:3](=[O:6])[C:26]([CH3:29])([CH3:25])[CH2:27][CH3:28]
Reactant: CCC(C)(C)[Mg]Cl
Reactant: COC(=O)C(=O)N1CC[C@H]1c1nnnn1CCCc1cccnc1
Agent: [Cl-]
Agent: [NH4+]
Solvent: C1CCOC1
Solvent: ClCCl
Solvent: CO
Product: CCC(C)(C)C(=O)C(=O)N1CC[C@H]1c1nnnn1CCCc1cccnc1
Temperature: -78 °C
Reaction time: 3 h
Yield: 8 %

Procedure:
(2S)-1-(1,2-Dioxo-2-methoxyethyl)-2-(1-[3-(3-pyridyl)-1-propyl]-1H-tetrazol-5-yl)azetidine from Reference Example 19 (95.8 mg, 0.290 mmol, 1.0 eq) was dissolved in dry tetrahydrofuran (THF) (1.0 mL) and cooled to about −78° C. under an argon atmosphere. To this solution, 1,1-dimethylpropylmagnesium chloride in THF (380 μL of 1M, 0.380 mmol, 1.3 eq) was introduced via syringe. After stirring the resulting homogeneous mixture at about −78° C. for about 3 hours, the mixture was poured into saturated ammonium chloride and extracted into ethyl acetate. The organic phase was washed with water, dried over sodium sulfate and concentrated. Flash chromatography of the residue (0-10% methanol in dichloromethane) afforded 8.7 mg (8% yield) of the product as a colorless semisolid along with 30.3 mg recovered starting material (32% yield). 1H NMR (CDCl3) δ 0.78 (t, 3H, J=6.9); 0.97-1.18 (series of s, 6H); 1.54 and 3.17 (series of m, 8H); 3.82-4.66 (series of m, 4H); 5.33-5.90 (series of dd, 1H); 7.21-7.31 (m, 1H); 7.57 (d, 1H, J=7.7); 8.49 (s, 2H).
Reaction SMILES: [Cl:1][C:2]1[CH:17]=[CH:16][C:5]2[O:6][CH2:7][O:8][C:9]3[CH:15]=[CH:14][CH:13]=[CH:12][C:10]=3[NH:11][C:4]=2[CH:3]=1.Br[CH2:19][CH2:20][CH2:21][Cl:22].[OH-].[Na+].C(C(C)=O)C>C1C=CC=CC=1>[Cl:1][C:2]1[CH:17]=[CH:16][C:5]2[O:6][CH2:7][O:8][C:9]3[CH:15]=[CH:14][CH:13]=[CH:12][C:10]=3[N:11]([CH2:19][CH2:20][CH2:21][Cl:22])[C:4]=2[CH:3]=1
Reactant: ClCCCBr
Reactant: Clc1ccc2c(c1)Nc1ccccc1OCO2
Agent: [Na+]
Agent: [OH-]
Solvent: CCC(C)=O
Solvent: c1ccccc1
Product: ClCCCN1c2ccccc2OCOc2ccc(Cl)cc21
Temperature: 20 °C
Reaction time: 10 h

Procedure:
A mixture of 14.9 g. (0.06 moles) of 2-chloro-12H-dibenzo[d,g][1,3,6]dioxazocine, 37.8 g. (0.24 moles) of 1-bromo-3-chloropropane, 19.6 g. (0.48 moles) of sodium hydroxide and 180 ml. of methyl ethyl ketone is stirred under reflux for 10 hours. Thereafter further 19.6 g. (0.48 moles) of sodium hydroxide are added and the stirring under reflux continued for 10 hours. The reaction mixture is cooled to 20° C. and poured to 300 g. of broken ice under stirring. 100 ml. of benzene are added, the organic phase is separated and the solvent is removed in vacuo. The residue is subjected to vacuum destillation. There are obtained 14.3 g. of a yellow viscous liquid, b.p./0.3 mmHg: 165° to 171° C. This liquid solidifies upon trituration with petrol ether. Recrystallization from isopropanol affords 12.5 g. (64.0%) of a white product, melting at 105° to 108° C.
Reaction SMILES: [Br:1][C:2]1[CH:10]=[CH:9][C:5]([CH2:6][CH2:7][OH:8])=[CH:4][CH:3]=1.[CH3:11][C:12](OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=[O:13].C(O)CO>C(Cl)Cl.C1(C)C=CC=CC=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>[Br:1][C:2]1[CH:10]=[CH:9][C:5]([CH2:6][CH:7]2[O:13][CH2:12][CH2:11][O:8]2)=[CH:4][CH:3]=1
Reactant: CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21
Reactant: OCCc1ccc(Br)cc1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: O
Solvent: ClCCl
Solvent: OCCO
Product: Brc1ccc(CC2OCCO2)cc1
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 48.8 %

Procedure:
To a cooled (0° C.) solution of 4-bromophenethylalcohol (3.9 g, 19.4 mmol) in DCM (50 mL), was added the Dess-Martin reagent (8.22 g, 19.4 mmol). After 10 minutes, the coolant was removed, and the reaction mixture was stirred at ambient temperature for 2 hours. The reaction mixture was quenched with 10% aqueous potassium carbonate, and the mixture was separated. The aqueous phase was extracted with further DCM (×2), and the combined organic phases were dried with anhydrous magnesium sulphate, and the solvent evaporated at reduced pressure. The crude material was purified by silica gel chromatography eluting with 100% iso-hexane to 50% ethyl acetate in iso-hexane to afford a oil. The oil was dissolved in toluene (35 mL), para-toluenesulfonic acid—monohydrate (0.1 g, 0.52 mmol) and ethylene glycol (5.3 mL, 94.2 mmol) was added, and the mixture heated at reflux under Dean and Stark conditions for 2 hours. The solvent was evaporated at reduced pressure and the residue dissolved in ethyl acetate. The solution was washed with 10% aqueous potassium carbonate, dried with anhydrous magnesium sulfate, and the solvent evaporated at reduced pressure. The crude material was purified by silica gel chromatography eluting with 100% iso-hexane to 50% ethyl acetate in iso-hexane to afford an oil (2.3 g, 49%).
Reaction SMILES: ClN1[C:6](=[O:7])[CH2:5]CC1=O.Br[C:10]1[C:24]2=[C:25]3[C:13]([N:14]([Si](C(C)(C)C)(C)C)[CH:15]=[C:16]3[CH2:17][C@@H:18]3[C@@H:23]2[CH2:22][C@H:21]([NH:26][C:27](=[O:33])[N:28]([CH2:31][CH3:32])[CH2:29][CH3:30])[CH2:20][N:19]3[CH3:34])=[CH:12][CH:11]=1>>[C:6]([C:11]1[CH:12]=[C:13]2[C:25]3[C:16]([CH2:17][C@@H:18]4[C@@H:23]([C:24]=3[CH:10]=1)[CH2:22][C@H:21]([NH:26][C:27](=[O:33])[N:28]([CH2:29][CH3:30])[CH2:31][CH3:32])[CH2:20][N:19]4[CH3:34])=[CH:15][NH:14]2)(=[O:7])[CH3:5]
Reactant: O=C1CCC(=O)N1Cl
Reactant: CCN(CC)C(=O)N[C@H]1C[C@@H]2c3c(Br)ccc4c3c(cn4[Si](C)(C)C(C)(C)C)C[C@H]2N(C)C1
Product: CCN(CC)C(=O)N[C@H]1C[C@@H]2c3cc(C(C)=O)cc4[nH]cc(c34)C[C@H]2N(C)C1

Procedure:
With N-chlorosuccinimide and 3-(12-bromo-1-tert-butyldimethylsilyl-6-methyl-8α-ergolinyl)-1,1-diethylurea:
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[C:9]([N+:10]([O-])=O)=[CH:8][NH:7][N:6]=1)=[O:4]>CCO.[Pd]>[CH3:1][O:2][C:3]([C:5]1[C:9]([NH2:10])=[CH:8][NH:7][N:6]=1)=[O:4]
Reactant: COC(=O)c1n[nH]cc1[N+](=O)[O-]
Agent: [Pd]
Solvent: CCO
Product: COC(=O)c1n[nH]cc1N
Reaction time: 20 h

Procedure:
A mixture of 4-nitro-1H-pyrazole-3-carboxylic acid methyl ester (34.6 mmol) and 10% Pd/C (650 mg) in EtOH (150 ml) is stirred under an atmosphere of hydrogen for 20 hours. The mixture is filtered through a plug of Celite, reduced in vacuo and dried through azeotrope with toluene to afford 4-amino-1H-pyrazole-3-carboxylic acid methyl ester
Reaction SMILES: [CH:1]1([C:8]2[CH:17]=[CH:16][C:11]3[NH:12][C:13](=[O:15])[O:14][C:10]=3[CH:9]=2)[CH2:6][CH2:5][C:4](=O)[CH2:3][CH2:2]1.[C:18]1([CH2:24][CH2:25][CH2:26][NH2:27])[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.[BH4-].[Na+]>CC(O)C>[C:18]1([CH2:24][CH2:25][CH2:26][NH:27][C@H:4]2[CH2:5][CH2:6][C@H:1]([C:8]3[CH:17]=[CH:16][C:11]4[NH:12][C:13](=[O:15])[O:14][C:10]=4[CH:9]=3)[CH2:2][CH2:3]2)[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1
Reactant: O=C1CCC(c2ccc3[nH]c(=O)oc3c2)CC1
Reactant: NCCCc1ccccc1
Agent: [BH4-]
Agent: [Na+]
Solvent: CC(C)O
Product: O=c1[nH]c2ccc([C@H]3CC[C@H](NCCCc4ccccc4)CC3)cc2o1
Reaction time: 4 h

Procedure:
To a solution of ketone 5 (0.50 g, 2.0 mmol) in 2-propanol (30 mL) was added 3 Å molecular sieves and 3-phenyl-1-propylamine 10 (0.39 g, 2.0 mmol). The reaction mixture was stirred for 4 hours. Sodium borohydride (0.11 g, 2.83 mmol) was added, and the reaction mixture was stirred overnight, quenched with MeOH, and concentrated under reduced pressure. Purification by flash chromatography (silica, 9.5:5:1 CH2Cl2:MeOH:NH4OH) gave 6-[trans-4-(3-phenylpropylamino)-cyclohexyl]-3H-benzoxazol-2-one (0.30 g, 42%): mp 166-170° C.; IR (KBr): 2933, 1761, 1653, 1582 cm−1; 1H NMR (500 MHz, DMSO-d6): δ 9.09 (s, 1H), 7.30-7.19 (m, 6H), 7.03 (d, J=9 Hz, 1H), 6.68 (d, J=9 Hz, 1H), 2.66 (m, 1H), 2.55 (t, J=8 Hz, 2H), 2.37 (tt, J=10, 2 Hz, 1H), 1.98 (d, J=10 Hz, 1H), 1.96 (d, J=10 Hz, 1H), 1.76 (d, J=3 Hz, 1H), 1.56 (m, 1H), 1.45 (m, 1H), 1.39 (m, 1H), 1.18-1.05 (m, 6H); CI-MS (methane) (m/z): 351 [M+H]+; HRMS-API (m/z): [M+H]+ calcd for C22H26N2O2, 351.2072; found, 351.2178; HPLC: method A, 7.66 minutes (96.9%); method B, 14.14 minutes (97.7%); Anal. Calcd for C22H26N2O2.H2O: C, 71.71; H, 7.66; N, 7.60. Found: C, 71.70; H, 7.62; N, 7.20.
Reaction SMILES: C([O:3][C:4]([C:6]1[CH:11]=[CH:10][C:9]([C@@H:12]([NH:14][S@@](C(C)(C)C)=O)[CH3:13])=[C:8]([F:21])[CH:7]=1)=[CH2:5])C.Cl>CO>[NH2:14][C@H:12]([C:9]1[CH:10]=[CH:11][C:6]([C:4](=[O:3])[CH3:5])=[CH:7][C:8]=1[F:21])[CH3:13]
Reactant: C=C(OCC)c1ccc([C@H](C)N[S@](=O)C(C)(C)C)c(F)c1
Agent: Cl
Solvent: CO
Product: CC(=O)c1ccc([C@H](C)N)c(F)c1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 103.7 %

Procedure:
To a round bottom flask containing (R)—N—((S)-1-(4-(1-ethoxyvinyl)-2-fluorophenyl)ethyl)-2-methylpropane-2-sulfinamide (600 mg, 1.91 mmol) was added MeOH (19 mL). To this homogenous solution was then added HCl (aq) (3.2 mL, 19.1 mmol, 3 M). Resulting reaction mixture was stirred at room temperature for 30 min. Volatiles were then removed. Residue triturated with Et2O to provide (S)-1-(4-(1-aminoethyl)-3-fluorophenyl)ethanone (0.43 g, 1.98 mmol, 103% yield) as a HCl salt. 1H NMR (400 MHz, D2O) δ 1.67 (d, J=6.99 Hz, 3H) 2.64 (s, 3H) 4.80-4.87 (m, 1H) 7.61 (t, J=7.73 Hz, 1H) 7.77 (dd, J=11.30, 1.66 Hz, 1H) 7.87 (dd, J=8.09, 1.64 Hz, 1H). LCMS m/z 182.0 (M+H)+, Rt 0.36 min.
Reaction SMILES: C([NH:4][N:5]1[CH2:10][C:9]([CH3:11])=[N:8][NH:7][C:6]1=[O:12])(=O)C.Cl.C([O-])(=O)C.[Na+]>CO>[NH2:4][N:5]1[CH2:10][C:9]([CH3:11])=[N:8][NH:7][C:6]1=[O:12]
Reactant: CC(=O)NN1CC(C)=NNC1=O
Agent: CC(=O)[O-]
Agent: Cl
Agent: [Na+]
Solvent: CO
Product: CC1=NNC(=O)N(N)C1
Temperature: 50 °C
Reaction time: 4 h

Procedure:
A mixture of 17 g of 4-acetylamino-6-methyl-3-oxo-2,3,4,5-tetrahydro-1,2,4-triazine, 63 ml of hydrochloric acid (37%) and 250 ml of methanol is stirred for 4 hours at 50° C. After cooling to 15° C., 82 g of sodium acetate are added, the mixture is stirred for a further 15 minutes, and the solvent is removed by evaporation. The residue is taken up in 100 ml of ethanol, and the solvent is removed again in vacuo. The residue is taken up in 1200 ml of acetonitrile, undissolved salt precipitates are filtered off, the filtrate is evaporated to dryness, the residue is caused to crystallise by adding 50 ml of acetic acid ethyl ester at ambient temperature, and the crystals are filtered off and dried yielding 54.6 g (85% of the theoretical amount) of the title compound having a melting point of 113°-118° C.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Cl:20])[C:7]=1[S:8][C:9]1[S:13][C:12]([C:14](Cl)=[O:15])=[CH:11][C:10]=1[N+:17]([O-:19])=[O:18].[CH3:21][S:22]([C:25]1[CH:31]=[CH:30][C:28]([NH2:29])=[CH:27][CH:26]=1)(=[O:24])=[O:23]>>[Cl:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Cl:20])[C:7]=1[S:8][C:9]1[S:13][C:12]([C:14]([NH:29][C:28]2[CH:27]=[CH:26][C:25]([S:22]([CH3:21])(=[O:24])=[O:23])=[CH:31][CH:30]=2)=[O:15])=[CH:11][C:10]=1[N+:17]([O-:19])=[O:18]
Reactant: CS(=O)(=O)c1ccc(N)cc1
Reactant: O=C(Cl)c1cc([N+](=O)[O-])c(Sc2c(Cl)cncc2Cl)s1
Product: CS(=O)(=O)c1ccc(NC(=O)c2cc([N+](=O)[O-])c(Sc3c(Cl)cncc3Cl)s2)cc1

Procedure:
Prepared according to the procedure described for example 50 from 5-[(3,5-dichloro-4-pyridyl)sulfanyl]-4-nitro-thiophene-2-carbonyl chloride (120 mg, 0.33 mmol) and 4-methylsulfonylaniline (66 mg, 0.39 mmol). The title compound was obtained as a yellow solid (60 mg, 37% yield). 1H NMR (400 MHz, d6-DMSO) δ: 10.88 (1H, m), 9.01 (2H, s), 8.87 (1H, s), 7.96 (4H, s), 3.20 (3H, s). MS m/z: 502.04, 503.99 [M+H]+.
Reaction SMILES: [F:1][C:2]([F:20])([F:19])[C:3]1[CH:4]=[CH:5][C:6]2[CH2:12][CH2:11][CH:10]([N:13]([CH2:16][CH3:17])[CH:14]=O)[CH2:9][CH2:8][C:7]=2[CH:18]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-].O.[OH-].[Na+]>CCOCC>[F:1][C:2]([F:19])([F:20])[C:3]1[CH:4]=[CH:5][C:6]2[CH2:12][CH2:11][CH:10]([N:13]([CH2:16][CH3:17])[CH3:14])[CH2:9][CH2:8][C:7]=2[CH:18]=1
Reactant: CCN(C=O)C1CCc2ccc(C(F)(F)F)cc2CC1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: O
Solvent: CCOCC
Product: CCN(C)C1CCc2ccc(C(F)(F)F)cc2CC1
Yield: 55.3 %

Procedure:
A solution of 285.3 g of 2-trifluoromethyl-7-(N-ethyl-N-formylamino)-6,7,8,9-tetrahydro-[5H]-benzocycloheptene in 3700 ml of anhydrous ether is introduced over a period of one hour into a suspension of 56 g of lithium aluminum hydride in 4700 ml of anydrous ether while stirring (a gentle reflux is observed). The whole is then heated at the boil for 5 hours. After cooling, the reaction mixture is hydrolysed in succession with 56 ml of water, 56 ml of a solution of 4N sodium hydroxide and 170 ml of water. After filtration and washing with ether, the organic layer is concentrated in vacuo and the residue is distilled off. 150 g of 2-trifluoromethyl-7-(N-ethyl-N-methylamino)-6,7,8,9-tetrahydro-[5H]-benzocycloheptene are obtained, b.p./10 mm =135°-140° C.
Reaction SMILES: [C:1]1(=[O:7])[CH2:5][CH2:4][C:3](=[O:6])[CH2:2]1.C1(C)C=CC=CC=1.C([O-])(=O)C.C([O-])(=O)C.C([O-])(=O)C.[Br:27][C:28]1[CH:29]=[CH:30][C:31]([CH:35]2[CH2:37][CH2:36]2)=[C:32]([Pb+3])[CH:33]=1>CN(C)C1C=CN=CC=1.C(Cl)(Cl)Cl.ClCCl.Cl>[Br:27][C:28]1[CH:33]=[CH:32][C:31]([CH:35]2[CH2:37][CH2:36]2)=[C:30]([CH:2]2[C:3](=[O:6])[CH2:4][CH2:5][C:1]2=[O:7])[CH:29]=1
Reactant: Brc1ccc(C2CC2)c([Pb+3])c1
Reactant: O=C1CCC(=O)C1
Agent: CC(=O)[O-]
Agent: CN(C)c1ccncc1
Agent: Cl
Solvent: Cc1ccccc1
Solvent: ClC(Cl)Cl
Solvent: ClCCl
Product: O=C1CCC(=O)C1c1cc(Br)ccc1C1CC1
Temperature: 80 °C

Procedure:
To a solution of cyclopentane-1,3-dione (0.57 g, 0.0058 mol) and 4-dimethylaminopyridine (3.64 g, 0.030 mol) in chloroform (33 ml) is added toluene (9 ml) then 5-bromo-2-cyclopropylphenyl lead triacetate (3.77 g, 0.0065 mol). This solution is heated at 80° C. for 20 hours then cooled to room temperature and diluted with dichloromethane and 2M aqueous hydrochloric acid. The resulting biphasic suspension is filtered through diatomaceous earth and the two phases are separated. The organic layer is further washed with 2M aqueous hydrochloric acid and the aqueous phase is extracted again with dichloromethane. All organic fractions are combined, washed with brine, dried over magnesium sulfate then concentrated in vacuo. The crude product is finally purified by flash column chromatography on silica gel (isohexane/ethyl acetate eluant) to afford 2-(5-bromo-2-cyclopropylphenyl)cyclopentane-1,3-dione as a pale yellow solid.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([O:15][CH2:16][C:17]2[C:22]([F:23])=[CH:21][CH:20]=[CH:19][C:18]=2[F:24])[C:5]2[N:6]([C:8]([C:12](O)=[O:13])=[C:9]([CH3:11])[N:10]=2)[CH:7]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN1CCOCC1.[NH2:56][CH2:57][CH:58]([NH:62][C:63](=[O:69])[O:64][C:65]([CH3:68])([CH3:67])[CH3:66])[CH:59]([CH3:61])[CH3:60].O.C(O)(C(F)(F)F)=O>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([O:15][CH2:16][C:17]2[C:18]([F:24])=[CH:19][CH:20]=[CH:21][C:22]=2[F:23])[C:5]2[N:6]([C:8]([C:12]([NH:56][CH2:57][CH:58]([NH:62][C:63](=[O:69])[O:64][C:65]([CH3:67])([CH3:66])[CH3:68])[CH:59]([CH3:61])[CH3:60])=[O:13])=[C:9]([CH3:11])[N:10]=2)[CH:7]=1
Reactant: Cc1nc2c(OCc3c(F)cccc3F)cc(Cl)cn2c1C(=O)O
Reactant: CC(C)C(CN)NC(=O)OC(C)(C)C
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: O=C(O)C(F)(F)F
Solvent: O
Solvent: CN1CCOCC1
Product: Cc1nc2c(OCc3c(F)cccc3F)cc(Cl)cn2c1C(=O)NCC(NC(=O)OC(C)(C)C)C(C)C
Temperature: 25 °C
Reaction time: 8 h

Procedure:
200 mg (0.57 mmol) of 6-chloro-8-[(2,6-difluorobenzyl)oxy]-2-methylimidazo[1,2-a]pyridine-3-carboxylic acid Example 16A, 191 mg (0.60 mmol) of HATU and 0.19 ml (1.70 mmol) of 4-methylmorpholine in DMF (3.6 ml) were stirred at RT for 20 min. 126 mg (0.62 mmol) of rac-tert-butyl (1-amino-3-methylbutan-2-yl)carbamate were then added and the reaction mixture was stirred at RT overnight. Water/TFA were then added and the mixture was purified by preparative RP-HPLC (acetonitrile/water gradient with addition of 0.1% TFA). The product fractions were concentrated and the residue was taken up in dichloromethane and washed twice with saturated aqueous sodium bicarbonate solution. The aqueous phase was extracted twice with dichloromethane and the combined organic phases were dried over sodium sulphate, filtered off and concentrated. This gave 264 mg (87% of theory, purity 100%) of the target compound.
Reaction SMILES: [Mg].[CH3:2][O:3][C:4]1[C:5]([O:18]COC)=[C:6](Br)[C:7]([CH3:16])=[C:8]([O:12]COC)[C:9]=1[O:10][CH3:11].C(Br)C.[C:25]([C:29]1[C:30](=[O:40])[C:31]([C:36]([CH3:39])([CH3:38])[CH3:37])=[CH:32][C:33](=O)[CH:34]=1)([CH3:28])([CH3:27])[CH3:26].[OH-].[Al+3].[Li+].[OH-].[OH-].[OH-].Cl>C(OC(=O)C)C>[C:36]([C:31]1[CH:32]=[C:33]([C:6]2[C:5](=[O:18])[C:4]([O:3][CH3:2])=[C:9]([O:10][CH3:11])[C:8](=[O:12])[C:7]=2[CH3:16])[CH:34]=[C:29]([C:25]([CH3:28])([CH3:27])[CH3:26])[C:30]=1[OH:40])([CH3:39])([CH3:38])[CH3:37]
Reactant: CC(C)(C)C1=CC(=O)C=C(C(C)(C)C)C1=O
Reactant: COCOc1c(C)c(Br)c(OCOC)c(OC)c1OC
Agent: Cl
Agent: [Al+3]
Agent: [Li+]
Solvent: CCOC(C)=O
Solvent: CCBr
Product: COC1=C(OC)C(=O)C(c2cc(C(C)(C)C)c(O)c(C(C)(C)C)c2)=C(C)C1=O
Reaction time: 2 h

Procedure:
A mixture was prepared by mixing 0.52 g of magnesium, 7.5 g of 3,4-dimethoxy-2,5-bismethoxymethoxy-6-methylbromobenzen and 0.2 ml of ethyl bromide into 30 ml of tetrahydrofurananhydride. The mixture was refluxed by heating until magnesium in the mixture disappears. The reaction mixture was cooled, 4.4 g 2,6-di-tert-butyl-p-benzoquinone was added thereinto, stirred for 2 hours, 1.5 g of lithium aluminium hydroxide was added thereinto, and stirred overnight at room temperature. An excess of hydrides in the reaction mixture was decomposed with ethylacetate, wherein 20 ml of 10% hydrochloric acid was added. The reaction mixture was stirred for 4 hours at room temperature, refluxed by heating for futher 2hours, cooled and extracted with diethylether. The extract was washed with 10% water solution of sodium hydrogencarbonate and an aqueous solution saturated with NaCl in turn, dried with sodium sulfate and concentrated. The concentrate was injected into a silica gel column-chromatography. The fraction eluted with the solvent (n-hexane:ethyl acetate=20:1) was concentrated, dissolved into 30 ml of methanol and stirred in addition of water solution of ferric chloride for 1hour, and then methanol in the reaction mixture was removed. The reactant was extracted with diethylether, and the extract was washed with an aqueous solution saturated with NaCl, dried with sodium sulfate and concentrate. The concentrated was recrystallized from ethylacetate/n-hexane to yield 0.5 g of reddish orange prism 2-(3,5-di-tert-butyl-4-hydroxyphenyl-5,6-dimethoxy-3-methyl-p-benzoquinone having a mp of 147.0°-148.0° C.
Reaction SMILES: [Si:1]([O:8][CH2:9][C:10]1[N:15]=[CH:14][C:13]2[N:16]([C:19]3[S:23][C:22]([C:24]([O:26]C)=O)=[C:21]([O:28][CH:29]([C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=4[Cl:37])[CH3:30])[CH:20]=3)[CH:17]=[N:18][C:12]=2[CH:11]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[NH3:38]>CO>[Si:1]([O:8][CH2:9][C:10]1[N:15]=[CH:14][C:13]2[N:16]([C:19]3[S:23][C:22]([C:24]([NH2:38])=[O:26])=[C:21]([O:28][CH:29]([C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=4[Cl:37])[CH3:30])[CH:20]=3)[CH:17]=[N:18][C:12]=2[CH:11]=1)([C:4]([CH3:5])([CH3:7])[CH3:6])([CH3:2])[CH3:3]
Reactant: N
Reactant: COC(=O)c1sc(-n2cnc3cc(CO[Si](C)(C)C(C)(C)C)ncc32)cc1OC(C)c1ccccc1Cl
Solvent: CO
Product: CC(Oc1cc(-n2cnc3cc(CO[Si](C)(C)C(C)(C)C)ncc32)sc1C(N)=O)c1ccccc1Cl

Procedure:
In a similar manner as described for example A7, 15.69 g of methyl 5-[6-({[tert-butyl(dimethyl)silyl]oxy}methyl)-3H-imidazo[4,5-c]pyridin-3-yl]-3-[-1-(2-chlorophenyl)ethoxy]thiophene-2-carboxylate and 1.4 l of a saturated solution of ammonia in methanol yield the title compound.
Reaction SMILES: [CH:1]12[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[C:2]1=[C:11]1[CH:18]3[CH2:19][CH:14]4[CH2:15][CH:16]([CH2:20][CH:12]1[CH2:13]4)[CH2:17]3)[CH2:8]2.[Cl:21]N1C(=O)CCC1=O.C1(C=CC(O)=CC=1)O>C(Cl)Cl>[Cl:21][C:1]12[CH2:8][CH:7]3[CH2:6][CH:5]([CH2:4][CH:3]([CH2:9]3)[C:2]1=[C:11]1[CH:12]3[CH2:20][CH:16]4[CH2:15][CH:14]([CH2:19][CH:18]1[CH2:17]4)[CH2:13]3)[CH2:10]2
Reactant: C1C2CC3CC1CC(C2)C3=C1C2CC3CC(C2)CC1C3
Reactant: O=C1CCC(=O)N1Cl
Agent: Oc1ccc(O)cc1
Solvent: ClCCl
Product: ClC12CC3CC(CC(C3)C1=C1C3CC4CC(C3)CC1C4)C2
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a solution of 1 mmol (268 mg) adamantylidene adamantane having the formula 19 in 20 cm3CH2Cl2, 1.05 mmoles (140 mg) N-chlorosuccinimide was added. The reaction mixture was stirred at room temperature for 1 hour, diluted with CH2Cl2, and washed twice with water. The organic layer was dried with MgSO4 and evaporated. The yield of 4-eq.-chloroadamantylideneadamantane was 300 mg (98%), melting point: 142°-143° C. (literature: 144°-145° C.). 1H NMR (CDCl3): δ 4.15 (br s, 1H); 3.05 (br s 1H); 2.8 (br s, 3H); 2.6-1.15 (br m, 22H) ppm. When 0.1 mmol hydroquinone was added to the solution, exactly the same reaction occurred, and the product could be isolated in virtually the same quantitative yield.
Reaction SMILES: [CH2:1]([OH:3])[CH3:2].[F:4][C:5]1[CH:10]=[CH:9][C:8]([P:11]([C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=2)Cl)=[CH:7][CH:6]=1.N>>[F:19][C:16]1[CH:17]=[CH:18][C:13]([P:11]([C:8]2[CH:9]=[CH:10][C:5]([F:4])=[CH:6][CH:7]=2)[O:3][CH2:1][CH3:2])=[CH:14][CH:15]=1
Reactant: CCO
Reactant: Fc1ccc(P(Cl)c2ccc(F)cc2)cc1
Agent: N
Product: CCOP(c1ccc(F)cc1)c1ccc(F)cc1
Temperature: 25 °C
Yield: 83.8 %

Procedure:
87 g (1.90 mol) of absolute ethanol are cooled to -15° C. under a nitrogen atmosphere. 67 g (0.26 mol) of bis-(4-fluorophenyl)chlorophosphine are then added dropwise at this temperature in 50 minutes with vigorous stirring. 5.2 g (0.31 mol) of ammonia gas are then introduced at this temperature. The mixture is then further stirred until room temperature is reached and stirred for a further 16 hours. The mixture is then filtered by suction and rinsed out with ethanol. The filtrate is freed from ethanol and excess ammonia in vacuo. The remaining residue is distilled at 0.45 mbar at an overhead temperature of 102° C. 58 g of ethyl bis-(4-fluorophenyl)-phosphinite are obtained. This corresponds to a yield of 84% of theory.