Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1[CH:15]=[C:14]2[C:5]([S:6][C:7]3[CH:8]=[C:9]([C:17]([OH:19])=O)[CH:10]=[CH:11][C:12]=3[C:13]2=[O:16])=[CH:4][CH:3]=1.S(Cl)([Cl:22])=O.CN(C)C=O>C1(C)C=CC=CC=1>[CH3:1][C:2]1[CH:15]=[C:14]2[C:5]([S:6][C:7]3[CH:8]=[C:9]([C:17]([Cl:22])=[O:19])[CH:10]=[CH:11][C:12]=3[C:13]2=[O:16])=[CH:4][CH:3]=1
Reactant: O=S(Cl)Cl
Reactant: Cc1ccc2sc3cc(C(=O)O)ccc3c(=O)c2c1
Solvent: CN(C)C=O
Solvent: Cc1ccccc1
Product: Cc1ccc2sc3cc(C(=O)Cl)ccc3c(=O)c2c1
Temperature: 25 °C
Reaction time: 16 h
Yield: 85 %

Procedure:
The 7-methyl-9-oxothioxanthene-3-carboxylic acid (MTA), 50.0 g (0.185 mol), was dissolved in 350 ml of toluene and 415 ml (5.69 mol) of thionyl chloride using an overhead stirrer in a 2 liter 3-neck round bottom flask. N,N-Dimethylformamide (DMF), 2 ml, was added and the reaction was brought to reflux for 2 hours. After this time, the mixture was stirred at room temperature for 16 hours. The solvent was removed under vacuum and the product was azeotroped with 3×350 ml of toluene to remove the excess thionyl chloride. The product was recrystallized from 800 ml of chloroform and the resulting solid was placed in a vacuum oven for 16 hours at 45° C. to complete removal of solvent. The isolated product weighed 45.31 g (85% yield) and nuclear magnetic resonance spectroscopy (NMR) confirmed the desired structure. This product was used for the preparation of a photoreactive monomer as described in Example 2.
Reaction SMILES: [CH2:1]([C:8]1[CH:9]=[N:10][C:11]2[C:16]([C:17]=1[C:18]1[CH:19]=[C:20]([NH2:24])[CH:21]=[CH:22][CH:23]=1)=[CH:15][CH:14]=[CH:13][C:12]=2[C:25]([F:28])([F:27])[F:26])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Br:29][C:30]1[S:34][C:33]([CH:35]=O)=[CH:32][CH:31]=1>>[CH2:1]([C:8]1[CH:9]=[N:10][C:11]2[C:16]([C:17]=1[C:18]1[CH:19]=[C:20]([NH:24][CH2:35][C:33]3[S:34][C:30]([Br:29])=[CH:31][CH:32]=3)[CH:21]=[CH:22][CH:23]=1)=[CH:15][CH:14]=[CH:13][C:12]=2[C:25]([F:28])([F:26])[F:27])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: Nc1cccc(-c2c(Cc3ccccc3)cnc3c(C(F)(F)F)cccc23)c1
Reactant: O=Cc1ccc(Br)s1
Product: FC(F)(F)c1cccc2c(-c3cccc(NCc4ccc(Br)s4)c3)c(Cc3ccccc3)cnc12

Procedure:
This compound was prepared according to the procedure of example 66, substituting 3-(3-benzyl-8-trifluoromethyl-quinolin-4-yl)-phenylamine and 5-bromo-thiophene-2-carbaldehyde. MS (ESI) m/z 553.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:23]=[CH:22][CH:21]=[CH:20][C:4]=1[CH2:5][NH:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[O:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.[O-:24][C:25]#[N:26].[K+].O>C(O)(=O)C>[NH2:26][C:25]([N:6]([CH2:5][C:4]1[CH:20]=[CH:21][CH:22]=[CH:23][C:3]=1[O:2][CH3:1])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[O:13][C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1)=[O:24]
Reactant: N#C[O-]
Reactant: COc1ccccc1CNc1ccccc1Oc1ccccc1
Agent: [K+]
Solvent: O
Solvent: CC(=O)O
Product: COc1ccccc1CN(C(N)=O)c1ccccc1Oc1ccccc1
Temperature: 25 °C
Reaction time: 2.5 h
Yield: 96.2 %

Procedure:
In 20 ml of acetic acid was dissolved 1.54 g of N-(2-methoxybenzyl)-2-phenoxyaniline synthesized in the same manner as in Example 1(1), and then an aqueous potassium cyanate solution (1.23 g of potassium cyanate and 10 ml of water) was added dropwise to the solution, followed by stirring at room temperature for 2.5 hours. The reaction mixture was poured into water and extracted with ethyl acetate, and the extract was washed with a saturated aqueous sodium bicarbonate solution and a saturated sodium chloride solution and dried over anhydrous sodium sulfate. After removal of the drying agent by filtration, the solvent was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (eluent; ethyl acetate−hexane=1:3) to give 1.69 g of N-aminocarbonyl-N-(2-methoxybenzyl)-2-phenoxyaniline as an oil.
Reaction SMILES: [CH2:1]([O:9][C:10]1[CH:15]=[CH:14][C:13]([N:16]2[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]2)=[CH:12][CH:11]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8].C(=O)([O-])[O-].[K+].[K+].F[C:29]1[CH:36]=[CH:35][C:32]([C:33]#[N:34])=[CH:31][CH:30]=1.O>CN(C)C=O.C(OCC)(=O)C>[CH2:1]([O:9][C:10]1[CH:11]=[CH:12][C:13]([N:16]2[CH2:21][CH2:20][N:19]([C:29]3[CH:36]=[CH:35][C:32]([C:33]#[N:34])=[CH:31][CH:30]=3)[CH2:18][CH2:17]2)=[CH:14][CH:15]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8]
Reactant: N#Cc1ccc(F)cc1
Reactant: CCCCCCCCOc1ccc(N2CCNCC2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CCCCCCCCOc1ccc(N2CCN(c3ccc(C#N)cc3)CC2)cc1
Temperature: 160 °C
Reaction time: 5 h
Yield: 82.9 %

Procedure:
To a suspension of 1-(4-n-Octyloxyphenyl)piperazine (1 g) and potassium carbonate (0.476 g) in N,N-dimethyl-formamide (1 ml) was added p-fluorobenzonitrile (0.347 g), and stirred for 5 hours at 160° C. The reaction mixture was added to a mixture of water and ethyl acetate. The organic layer was taken, and dried over magnesium sulfate. The magnesium sulfate was filtered off, and the filtrate was evaporated under reduced pressure to give 4-[4-(4-n-Octyloxyphenyl)piperazin-1-yl]benzonitrile (0.93 g).
Reaction SMILES: [Cl:1][C:2]1[N:3]=[N:4][C:5]([CH3:9])=[C:6](Cl)[N:7]=1.[CH2:10]([O:17][C:18]1[CH:23]=[CH:22][C:21](B(O)O)=[CH:20][C:19]=1[O:27][CH3:28])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C(COC)OC.C(Cl)(Cl)Cl.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:10]([O:17][C:18]1[CH:23]=[CH:22][C:21]([C:6]2[N:7]=[C:2]([Cl:1])[N:3]=[N:4][C:5]=2[CH3:9])=[CH:20][C:19]=1[O:27][CH3:28])[C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1
Reactant: COc1cc(B(O)O)ccc1OCc1ccccc1
Reactant: Cc1nnc(Cl)nc1Cl
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=P([O-])([O-])[O-]
Agent: [K+]
Solvent: ClC(Cl)Cl
Solvent: COCCOC
Product: COc1cc(-c2nc(Cl)nnc2C)ccc1OCc1ccccc1
Temperature: 25 °C

Procedure:
A degassed solution of 3,5-dichloro-6-methyl-1,2,4-triazine (151 mg, 0.9 mmol), 4-(benzyloxy)-3-methoxybenzene boronic acid (236 g, 0.9 mmol), tetrakis(triphenylphosphine)palladium(0) (55 mg, 0.05 mmol) and tripotassium phosphate (249 mg, 1.2 mmol) in dimethoxyethane (5 mL) was heated at reflux for 24 h. Upon cooling to room temperature the solution was diluted with CHCl3 and filtered through Celite®. The filtrate was concentrated in vacuo and the product purified by column chromatography using ethyl acetate-hexane (25:75) as eluent to furnish (75 mg, 22%).
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][C:6]([NH:10][C:11]3[C:20]4[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=4)[N:14]=[C:13]([C:21]4[CH:22]=[C:23]([CH:29]=[CH:30][CH:31]=4)[O:24][CH2:25][C:26](O)=[O:27])[N:12]=3)=[CH:7][CH:8]=2)[CH:3]=[N:2]1.C1CN([P+](ON2N=[N:56][C:51]3[CH:52]=[CH:53][CH:54]=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.C1(CN)CC1>C(Cl)Cl.CN(C=O)C>[NH:1]1[C:9]2[C:4](=[CH:5][C:6]([NH:10][C:11]3[C:20]4[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=4)[N:14]=[C:13]([C:21]4[CH:22]=[C:23]([CH:29]=[CH:30][CH:31]=4)[O:24][CH2:25][C:26]([NH:56][CH2:51][CH:52]4[CH2:54][CH2:53]4)=[O:27])[N:12]=3)=[CH:7][CH:8]=2)[CH:3]=[N:2]1
Reactant: c1ccc2c(c1)nnn2O[P+](N1CCCC1)(N1CCCC1)N1CCCC1
Reactant: O=C(O)COc1cccc(-c2nc(Nc3ccc4[nH]ncc4c3)c3ccccc3n2)c1
Agent: F[P-](F)(F)(F)(F)F
Agent: NCC1CC1
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: O=C(COc1cccc(-c2nc(Nc3ccc4[nH]ncc4c3)c3ccccc3n2)c1)NCC1CC1
Reaction time: 0.5 h

Procedure:
A suspension of 2-(3-(4-(1H-indazol-5-ylamino)quinazolin-2-yl)phenoxy)acetic acid (80 mg, 0.16 mmol), PyBOP® (46 mg, 0.088 mmol), DIEA (28 μL, 0.16 mmol) in dry CH2Cl2:DMF (2:0.1 mL) was stirred at RT for 15 minutes. To this solution of activated acid was added cyclopropylmethanamine (7.1 mg, 0.10 mmol). After 30 minutes, 1.0 equivalent of DIEA and 0.55 equivalents of PyBOP® were added. After stirring the solution for 15 minutes, 0.65 equivalents of cyclopropylmethanamine were added and the mixture was stirred for an additional 30 minutes. The solvent was removed in vacuo and the crude product was purified using prep HPLC (20-45—90 mins) to afford 2-(3-(4-(1H-indazol-5-ylamino)quinazolin-2-yl)phenoxy)-N-(cyclopropylmethyl)acetamide. (60 mg, 0.13 mmol, 81%)
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][N:9]2[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]2)=[CH:4][C:3]=1[NH:15][C@@H:16]1[CH2:21][CH2:20][C@H:19]([C:22]([NH:24][CH:25]([CH3:27])[CH3:26])=[O:23])[CH2:18][CH2:17]1.[CH3:28][O:29][C:30]([NH:32][C:33](=NC(OC)=O)SC)=[O:31].O.C1(C)C=CC(S(O)(=O)=O)=CC=1.C(Cl)Cl>CO>[CH:25]([NH:24][C:22]([C@@H:19]1[CH2:20][CH2:21][C@H:16]([N:15]2[C:3]3[CH:4]=[C:5]([CH2:8][N:9]4[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14]4)[CH:6]=[CH:7][C:2]=3[N:1]=[C:33]2[NH:32][C:30](=[O:31])[O:29][CH3:28])[CH2:17][CH2:18]1)=[O:23])([CH3:27])[CH3:26]
Reactant: CC(C)NC(=O)[C@H]1CC[C@@H](Nc2cc(CN3CCCCC3)ccc2N)CC1
Reactant: COC(=O)N=C(NC(=O)OC)SC
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: ClCCl
Solvent: CO
Solvent: O
Product: COC(=O)Nc1nc2ccc(CN3CCCCC3)cc2n1[C@H]1CC[C@@H](C(=O)NC(C)C)CC1
Temperature: 80 °C

Procedure:
To a solution of cis-4-(2-amino-5-(piperidin-1-ylmethyl)phenylamino)-N-isopropylcyclohexanecarboxamide (0.300 g, 0.805 mmol) in MeOH (4.5 mL) was added 1,3-bis(methoxycarbonyl)-2-methyl-2-thiopseudourea (0.166 g, 0.805 mmol) and p-toluenesulfonic acid monohydrate (0.168 g, 0.886 mmol). The reaction mixture was heated at 80° C. for 2 hours and then concentrated under vacuum. The residue was dissolved in DCM and was washed with saturated aqueous NaHCO3. The organic layer was dried over sodium sulfate and concentrated under vacuum. The residue was purified by flash chromatography, eluting with 0-100% 90:10:1 DCM/MeOH/NH4OH:DCM to afford methyl 1-(cis-4-(isopropylcarbamoyl)cyclohexyl)-6-(piperidin-1-ylmethyl)-1H-benzo[d]imidazol-2-ylcarbamate (0.239 g, 65.1% yield). MS, m/z (C25H37N5O3); calcd, 455.59. found 456.2 [M+H]. 1H NMR (400 MHz, CDCl3) δ ppm 1.23 (d, J=6.55 Hz, 6H) 1.38-1.49 (m, 2H) 1.52-1.67 (m, 4H) 1.67-1.85 (m, 6H) 2.10-2.20 (m, 2H) 2.34-2.51 (m, 4H) 2.58-2.73 (m, 2H) 3.54-3.66 (m, 1H) 3.79 (s, 3H) 4.20 (dt, J=13.70, 6.70 Hz, 1H) 4.86 (tt, J=12.79, 4.47 Hz, 1H) 5.34 (br. d, J=7.20 Hz, 1H) 7.13-7.25 (m, 2H) 7.61 (br. s., 1H) 11.29 (br. s., 1H).
Reaction SMILES: [N:1]([C:4]1[CH:5]=[C:6]([CH:9]=[CH:10][CH:11]=1)[C:7]#[N:8])=[C:2]=[O:3].[Br:12][C:13]1[CH:18]=[CH:17][C:16]([CH2:19][CH2:20][CH2:21][NH:22][CH3:23])=[CH:15][CH:14]=1>C(Cl)Cl>[Br:12][C:13]1[CH:14]=[CH:15][C:16]([CH2:19][CH2:20][CH2:21][N:22]([CH3:23])[C:2]([NH:1][C:4]2[CH:11]=[CH:10][CH:9]=[C:6]([C:7]#[N:8])[CH:5]=2)=[O:3])=[CH:17][CH:18]=1
Reactant: N#Cc1cccc(N=C=O)c1
Reactant: CNCCCc1ccc(Br)cc1
Solvent: ClCCl
Product: CN(CCCc1ccc(Br)cc1)C(=O)Nc1cccc(C#N)c1
Reaction time: 8 h
Yield: 82.5 %

Procedure:
3-Isocyanatobenzonitrile (202 mg, 1.4 mmol) was added in one portion to a solution of 22B (320 mg, 1.4 mmol) in methylene chloride (10 mL). After stirring overnight the reaction mixture was concentrated in vacuo and purified by flash chromatography (0 to 100% EtOAc in hexanes) to yield 22C (430 mg, 88%) as a clear oil. MS (ESI) m/z 371.92/373.92 (M+H)+.
Reaction SMILES: [Cl:1][C:2]([Cl:45])([Cl:44])[C:3]([O:6][C:7]([N:9]1[CH:14]2[C:15]([C:34](O)=[O:35])=[C:16]([C:18]3[O:22][N:21]=[C:20]([CH2:23][CH2:24][CH2:25][O:26][Si:27]([C:30]([CH3:33])([CH3:32])[CH3:31])([CH3:29])[CH3:28])[CH:19]=3)[CH2:17][CH:10]1[CH2:11][N:12]([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[CH2:13]2)=[O:8])([CH3:5])[CH3:4].[CH:46]1([NH:49][CH2:50][C:51]2[CH:56]=[CH:55][CH:54]=[C:53]([Cl:57])[C:52]=2[Cl:58])[CH2:48][CH2:47]1.CCN(C(C)C)C(C)C.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl>CN(C1C=CN=CC=1)C.C(Cl)Cl>[Cl:44][C:2]([Cl:1])([Cl:45])[C:3]([O:6][C:7]([N:9]1[CH:14]2[C:15]([C:34](=[O:35])[N:49]([CH:46]3[CH2:47][CH2:48]3)[CH2:50][C:51]3[CH:56]=[CH:55][CH:54]=[C:53]([Cl:57])[C:52]=3[Cl:58])=[C:16]([C:18]3[O:22][N:21]=[C:20]([CH2:23][CH2:24][CH2:25][O:26][Si:27]([C:30]([CH3:33])([CH3:32])[CH3:31])([CH3:29])[CH3:28])[CH:19]=3)[CH2:17][CH:10]1[CH2:11][N:12]([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[CH2:13]2)=[O:8])([CH3:4])[CH3:5]
Reactant: Clc1cccc(CNC2CC2)c1Cl
Reactant: CC(C)(C)OC(=O)N1CC2CC(c3cc(CCCO[Si](C)(C)C(C)(C)C)no3)=C(C(=O)O)C(C1)N2C(=O)OC(C)(C)C(Cl)(Cl)Cl
Agent: CCN=C=NCCCN(C)C
Agent: CN(C)c1ccncc1
Agent: Cl
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: CC(C)(C)OC(=O)N1CC2CC(c3cc(CCCO[Si](C)(C)C(C)(C)C)no3)=C(C(=O)N(Cc3cccc(Cl)c3Cl)C3CC3)C(C1)N2C(=O)OC(C)(C)C(Cl)(Cl)Cl
Temperature: 25 °C
Yield: 35.2 %

Procedure:
A mixture of compound D3 (355 mg, 0.500 mmol), cyclopropyl-(2,3-dichlorobenzyl)-amine (prepared from 2,3-dichlorobenzaldehyde and cyclopropylamine by reductive amination, 324 mg, 1.50 mmol), DIPEA (0.342 mL, 2.00 mmol), DMAP (15.3 mg, 0.125 mmol), HOBt (101 mg, 0.75 mmol) and EDC.HCl (288 mg, 1.50 mmol) in CH2Cl2 (7 mL) was stirred at rt for 2 weeks. The mixture was diluted with more CH2Cl2, and washed with aq. 1M HCl (3×) and aq. sat. NaHCO3 (1×). The org. extracts were dried over MgSO4, filtered, and the solvents were removed under reduced pressure. Purification of the residue by FC (EtOAc/heptane 1:9→2:8 3:7→4:6→1:1) yielded the title compound (160 mg, 35%). LC-MS: tR=1.34 min, ES+: 909.35.
Reaction SMILES: [OH:1][CH2:2][C@@:3]12[C@@H:20]3[C@H:11]([C@H:12]4[C@@:16]([CH2:18][CH2:19]3)([CH3:17])[CH2:15][CH2:14][CH2:13]4)[CH2:10][CH2:9][C:8]1=[CH:7][C:6](=[O:21])[CH2:5][CH2:4]2.[BH4-].[K+].O.C(O)(=[O:27])C>C(O)C>[OH:27][C@H:15]1[CH2:14][CH2:13][C@H:12]2[C@H:11]3[C@H:20]([CH2:19][CH2:18][C@:16]12[CH3:17])[C@:3]1([CH2:2][OH:1])[C:8](=[CH:7][C:6](=[O:21])[CH2:5][CH2:4]1)[CH2:9][CH2:10]3
Reactant: CC(=O)O
Reactant: C[C@@]12CCC[C@H]1[C@@H]1CCC3=CC(=O)CC[C@]3(CO)[C@H]1CC2
Agent: [BH4-]
Agent: [K+]
Solvent: CCO
Solvent: O
Product: C[C@]12CC[C@H]3[C@@H](CCC4=CC(=O)CC[C@@]43CO)[C@@H]1CC[C@@H]2O
Temperature: 0 °C
Reaction time: 1 h

Procedure:
A solution of 150 g of 19-hydroxyandrost-4-en-3-one in 6 liters of ethanol is cooled in an ice bath. To this cold solution is added 13.5 g of potassium borohydride, and the reaction mixture is stirred for two hours at about 0 ° C after which a second 13.5 g or potassium borohydride is added. Two hours later a third 13.5 g portion of potassium borohydride is added to the reaction mixture which is stirred for an additional 1 hour then poured into 11 liters of water which 70 ml of acetic acid is added. The ethanol is distilled off under reduced pressure and the aqueous residue cooled to 0° C. The solid which separates is filtered off, dried and dissolved in 25 liters of hot chloroform after which the temperature is adjusted to 25° C. To the chloroform solution is added 250 g of manganese dioxide, and the mixture is stirred for 2 hours then filtered and the solvents removed under reduced pressure. The solid residue is recrystallized from acetonitrile to give 17β,19-dihydroxyandrost-4-en-3-one. M.P. 205°-207° C.
Reaction SMILES: [CH2:1]([N:8]1[CH:12]=[CH:11][N:10]=[C:9]1[C:13]1[CH:14]=[N:15][CH:16]=[CH:17][CH:18]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:19]([C:21]1[CH:22]=[N:23][CH:24]=[CH:25][CH:26]=1)#[N:20].B(O)(O)[C:28]1[CH:33]=CC=[C:30](F)[CH:29]=1>ClCCl.CO>[C:25]1([C:24]2[N:20]=[CH:19][C:21]([C:12]3[NH:8][C:9]([C:13]4[CH:14]=[N:15][CH:16]=[CH:17][CH:18]=4)=[N:10][CH:11]=3)=[CH:22][N:23]=2)[CH:26]=[CH:30][CH:29]=[CH:28][CH:33]=1.[CH2:1]([N:8]1[CH:12]=[CH:11][N:10]=[C:9]1[C:13]1[CH:14]=[N:15][CH:16]=[CH:17][CH:18]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: OB(O)c1cccc(F)c1
Reactant: N#Cc1cccnc1
Agent: c1ccc(Cn2ccnc2-c2cccnc2)cc1
Solvent: ClCCl
Solvent: CO
Product: c1ccc(-c2ncc(-c3cnc(-c4cccnc4)[nH]3)cn2)cc1

Procedure:
The title compound was prepared by the method described in Example 1, except that 3-(1-benzyl-1H-imidazol-2-yl)pyridine was used instead of 1-benzyl-2-phenyl-1H-imidazole in Step C. 3-(1-Benzyl-1H-imidazol-2-yl)pyridine was prepared by the method described in Example 8, Steps A and B except the commercially available 3-cyanopyridine was used instead of 3-fluorobenzonitrile; Rf 0.25 with 95:5 v/v dichloromethane-methanol; melting point 308° C; 1H-NMR (400 MHz; DMSO-d6) δ 9.32 (s, 2H), 9.20 (d, 1H), 8.58 (dd, 1H), 8.44-8.31 (m, 3H), 8.12 (m, 1H), 7.57-7.46 (m, 4H); MS (ESI+) m/z 300.1 (M+1); H-PGDS FPBA IC50: 0.079 μM; H-PGDS inhibitor EIA IC50: 0.021 μM.
Reaction SMILES: [C:1]([O:7][CH3:8])(=[O:6])[CH2:2][C:3]([O-])=O.[K+].[C:10]([C:13]1[CH:20]=[CH:19][C:16](C=O)=[CH:15][CH:14]=1)([OH:12])=[O:11].N1CCCCC1.C(=O)=O.Cl>N1C=CC=CC=1>[CH3:8][O:7][C:1]([CH:2]=[CH:3][C:16]1[CH:19]=[CH:20][C:13]([C:10]([OH:12])=[O:11])=[CH:14][CH:15]=1)=[O:6]
Reactant: COC(=O)CC(=O)[O-]
Reactant: O=Cc1ccc(C(=O)O)cc1
Agent: Cl
Agent: O=C=O
Agent: [K+]
Solvent: c1ccncc1
Solvent: C1CCNCC1
Product: COC(=O)C=Cc1ccc(C(=O)O)cc1
Temperature: 0 °C

Procedure:
18.74 g (0.12 mol) of potassium monomethyl malonate were suspended in 18 ml of pyridine. 15.01 g (0.1 mol) of 4-carboxybenzaldehyde and 0.85 g (0.01 mol) of piperidine were added at room temperature with stirring and the mixture was boiled under reflux until the evolution of carbon dioxide had ceased (about 2 h). A further 60 ml of pyridine were added and the mixture was stirred under reflux for a further 1 h. The reaction mixture was treated with stirring with 500 ml of ice and 110 ml of concentrated hydrochloric acid. After the addition was complete, the mixture was stirred for a further 20 min, and the product was filtered off with suction, washed with water and recrystallized from isopropanol. Yield: 12.85 g (62%).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH:14]2[O:23][C:17]3=[CH:18][N:19]=[C:20](Cl)[CH:21]=[C:16]3[CH2:15]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:24][O:25][C:26]1[CH:31]=[C:30](B(O)O)[CH:29]=[CH:28][N:27]=1>>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH:14]2[O:23][C:17]3=[CH:18][N:19]=[C:20]([C:30]4[CH:29]=[CH:28][N:27]=[C:26]([O:25][CH3:24])[CH:31]=4)[CH:21]=[C:16]3[CH2:15]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)OC(=O)N1CCC(C2Cc3cc(Cl)ncc3O2)CC1
Reactant: COc1cc(B(O)O)ccn1
Product: COc1cc(-c2cc3c(cn2)OC(C2CCN(C(=O)OC(C)(C)C)CC2)C3)ccn1

Procedure:
The title compound is prepared from 4-(5-chloro-2,3-dihydro-furo[2,3-c]pyridin-2-yl)-piperidine-1-carboxylic acid tert-butyl ester and 2-methoxypyridine-4-boronic acid following a procedure analogous to that described in Example 28. LC (method 10): tR=1.76 min; Mass spectrum (ESI+): m/z=412 [M+H]+.
Reaction SMILES: CC(C)([O-])C.[K+].[CH3:7][O:8][C:9]1[C:20]([O:21][CH3:22])=[CH:19][C:12]2[CH2:13][C:14](=[O:18])[NH:15][CH:16]=[CH:17][C:11]=2[CH:10]=1.[CH2:23]([N:30]1[CH2:36][CH2:35][CH2:34][CH2:33][CH:32]([CH2:37]Br)[CH2:31]1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>CS(C)=O.C(OCC)(=O)C>[CH2:23]([N:30]1[CH2:36][CH2:35][CH2:34][CH2:33][CH:32]([CH2:37][N:15]2[C:14](=[O:18])[CH2:13][C:12]3[CH:19]=[C:20]([O:21][CH3:22])[C:9]([O:8][CH3:7])=[CH:10][C:11]=3[CH:17]=[CH:16]2)[CH2:31]1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1
Reactant: BrCC1CCCCN(Cc2ccccc2)C1
Reactant: COc1cc2c(cc1OC)CC(=O)NC=C2
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: CS(C)=O
Solvent: CCOC(C)=O
Product: COc1cc2c(cc1OC)CC(=O)N(CC1CCCCN(Cc3ccccc3)C1)C=C2
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
2.3 g (0.02 mol) of potassium tert.butoxide are added to a solution of 4.4 g (0.02 mol) of 7,8-dimethoxy-1,3-dihydro-2H-3-benzazepin-2-one in 100ml of absolute dimethylsulphoxide. After stirring for 30 minutes at ambient temperature, 5.6 g (0.020 mol) of 1-benzyl-3-bromomethyl-hexahydro-azepine are added and the resulting mixture is stirred for 2 hours at ambient temperature. The reaction mixture is dissolved in ethyl acetate and extracted several times with water. The organic phase is dried over magnesium sulphate and evaporated down in vacuo. The residue is purified by column chromatography over aluminium oxide N (activity II, eluant: methylene chloride, methylene chloride+0.3% ethanol). Yield: 4.2 g (50% of theory), IR spectrum (methylene chloride): 1655 cm-1 (CO).
Reaction SMILES: [O:1]([C:8]1[CH:9]=[C:10]([CH:14]=[CH:15][CH:16]=1)[CH2:11][C:12]#[N:13])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:17](Cl)[CH2:18][CH2:19][CH3:20].[OH-].[Na+]>[Br-].C([N+](CC)(CC)CC)C.O>[O:1]([C:8]1[CH:9]=[C:10]([CH:11]([CH2:17][CH2:18][CH2:19][CH3:20])[C:12]#[N:13])[CH:14]=[CH:15][CH:16]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: N#CCc1cccc(Oc2ccccc2)c1
Reactant: CCCCCl
Agent: CC[N+](CC)(CC)CC
Agent: [Br-]
Agent: [Na+]
Solvent: O
Product: CCCCC(C#N)c1cccc(Oc2ccccc2)c1
Yield: 54.8 %

Procedure:
Into a three-necked 500 ml round-bottom flask are charged 35 g (0.17 mole) of m-phenoxybenzyl cyanide, 16.3 g (0.17 mole) of butyl chloride 4 g of tetraethylammonium bromide. To this mixture is added 27 g (0.34 mole) of 50% sodium hydroxide solution dropwise with stirring. The reaction mixture is heated at 90° for three hours. It is then poured into water and extracted with hexane. The combined hexane extracts are washed with water and dried over MgSO4. Solvent is evaporated to give 39 g of crude product. Vacuum distillation (149°-155°/0.2 mm) provides 24.7 g of pure product.
Reaction SMILES: [OH:1][CH2:2][CH:3]1[CH2:9][C:8]2[CH:10]=[C:11]3[O:16][CH2:15][O:14][C:12]3=[CH:13][C:7]=2[C:6]([C:17]2[CH:22]=[CH:21][C:20]([N+:23]([O-:25])=[O:24])=[CH:19][CH:18]=2)=[N:5][NH:4]1.C(N(CC)CC)C.[C:33](Cl)(Cl)=[O:34]>C1(C)C=CC=CC=1>[N+:23]([C:20]1[CH:21]=[CH:22][C:17]([C:6]2[C:7]3[CH:13]=[C:12]4[O:14][CH2:15][O:16][C:11]4=[CH:10][C:8]=3[CH2:9][CH:3]3[CH2:2][O:1][C:33](=[O:34])[N:4]3[N:5]=2)=[CH:18][CH:19]=1)([O-:25])=[O:24]
Reactant: O=C(Cl)Cl
Reactant: O=[N+]([O-])c1ccc(C2=NNC(CO)Cc3cc4c(cc32)OCO4)cc1
Solvent: Cc1ccccc1
Solvent: CCN(CC)CC
Product: O=C1OCC2Cc3cc4c(cc3C(c3ccc([N+](=O)[O-])cc3)=NN12)OCO4
Yield: 67 %

Procedure:
A solution of 1.0 g (2.93 mmol) of 8-hydroxymethyl-5-(4-nitrophenyl)-8,9-dihydro-7H-1,3-dioxolo[4,5-h][2,3]benzodiazepine is mixed in succession with 0.98 ml (7.03 mmol) of triethylamine and 2.23 ml (3.52 mmol) of a 15.6% phosgene solution in toluene while being stirred and cooled. Then, the reaction mixture is heated for 3 hours to 25° C. The precipitate of the crude product is separated, the filtrate is concentrated by evaporation and the residue is treated with water. The combined residues are boiled with ethanol, and after suctioning-off, 0.72 g (67%) of the title compound with a melting point >250° C. (decomposition) is obtained.