Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(OC([N:8]([S:60]([C:63]1[CH:68]=[CH:67][C:66]([CH3:69])=[CH:65][CH:64]=1)(=[O:62])=[O:61])[CH2:9][CH2:10][CH2:11][CH2:12][N:13]([C:52](=[O:59])[C:53]1[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=1)[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][N:21]([C:44](=[O:51])[C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1)[CH2:22][CH2:23][CH2:24][CH2:25][N:26](C(OC(C)(C)C)=O)[S:27]([C:30]1[CH:35]=[CH:34][C:33]([CH3:36])=[CH:32][CH:31]=1)(=[O:29])=[O:28])=O)(C)(C)C>Cl>[CH3:36][C:33]1[CH:32]=[CH:31][C:30]([S:27]([NH:26][CH2:25][CH2:24][CH2:23][CH2:22][N:21]([C:44](=[O:51])[C:45]2[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=2)[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16][CH2:15][CH2:14][N:13]([C:52](=[O:59])[C:53]2[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=2)[CH2:12][CH2:11][CH2:10][CH2:9][NH:8][S:60]([C:63]2[CH:64]=[CH:65][C:66]([CH3:69])=[CH:67][CH:68]=2)(=[O:62])=[O:61])(=[O:28])=[O:29])=[CH:35][CH:34]=1
Reactant: Cc1ccc(S(=O)(=O)N(CCCCN(CCCCCCCN(CCCCN(C(=O)OC(C)(C)C)S(=O)(=O)c2ccc(C)cc2)C(=O)c2ccccc2)C(=O)c2ccccc2)C(=O)OC(C)(C)C)cc1
Agent: Cl
Product: Cc1ccc(S(=O)(=O)NCCCCN(CCCCCCCN(CCCCNS(=O)(=O)c2ccc(C)cc2)C(=O)c2ccccc2)C(=O)c2ccccc2)cc1

Procedure:
Dissolve 1,19-Bis(tert-butyloxycarbonyl)-1,19-bis[(4-methylphenyl)sulfonyl]-6,14-bis(benzoyl)-1,6,14,19-tetraazanonadecane (9.76 g, 10 mmol) in saturated methanolic hydrochloric acid (100 mL). Stir for several hours and evaporate the solvent in vacuo. Dissolve the residue in water and neutralize with saturated sodium hydrogen carbonate and extract with ethyl acetate. Dry (MgSO4) and evaporate the solvent in vacuo. Purify by silica gel chromatography to give the title compound.
Reaction SMILES: Br[C:2]1[C:10]2[C:5](=[CH:6][C:7]([C:11]3[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=3)=[CH:8][CH:9]=2)[N:4]([C:19]2[N:24]=[CH:23][N:22]=[C:21]([NH:25][CH3:26])[CH:20]=2)[CH:3]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].CC1(C)C(C)(C)OB([C:43]2[CH:51]=[C:50]3[C:46]([CH:47]=[CH:48][NH:49]3)=[CH:45][CH:44]=2)O1.C(OCC)(=O)C>CN(C)C=O.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.O>[CH3:18][O:17][C:14]1[CH:15]=[CH:16][C:11]([C:7]2[CH:6]=[C:5]3[C:10]([C:2]([C:43]4[CH:51]=[C:50]5[C:46]([CH:47]=[CH:48][NH:49]5)=[CH:45][CH:44]=4)=[CH:3][N:4]3[C:19]3[N:24]=[CH:23][N:22]=[C:21]([NH:25][CH3:26])[CH:20]=3)=[CH:9][CH:8]=2)=[CH:12][CH:13]=1
Reactant: CNc1cc(-n2cc(Br)c3ccc(-c4ccc(OC)cc4)cc32)ncn1
Reactant: CC1(C)OB(c2ccc3cc[nH]c3c2)OC1(C)C
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: CN(C)C=O
Solvent: O
Solvent: CCOC(C)=O
Product: CNc1cc(-n2cc(-c3ccc4cc[nH]c4c3)c3ccc(-c4ccc(OC)cc4)cc32)ncn1
Temperature: 120 °C
Reaction time: 3 h

Procedure:
6-(3-Bromo-6-(4-methoxyphenyl)-1H-indol-1-yl)-N-methylpyrimidin-4-amine (50 mg, 0.074 mmol), K3PO4 (47.1 mg, 0.222 mmol) and 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole (27 mg, 0.111 mmol) were dissolved in dimethylformamide (2 mL) and then Pd(PPh3)4 (12.83 mg, 0.011 mmol) was added. After stirring at 120° C. for 3 hours, followed by addition of ethyl acetate and water, the reaction solution was filtered using a diatomite pad. The aqueous layer was extracted with ethyl acetate and the collected organic layer was washed with brine and then concentrated under reduced pressure by drying with magnesium sulfate. The residue was purified by chromatography (silica gel, EtOAc:hexane=1:10→1:4→1:2). The target compound was obtained as brown solid.
Reaction SMILES: CCN(C(C)C)C(C)C.[F:10][C:11]1[CH:19]=[CH:18][C:17]([F:20])=[CH:16][C:12]=1[C:13]([OH:15])=O.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.[O:43]=[C:44]([N:61]1[CH2:66][CH2:65][NH:64][CH2:63][CH2:62]1)[CH2:45][NH:46][C:47]([C:49]1[CH:54]=[CH:53][C:52]([C:55]2[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=2)=[CH:51][CH:50]=1)=[O:48]>CN(C=O)C.O>[F:10][C:11]1[CH:19]=[CH:18][C:17]([F:20])=[CH:16][C:12]=1[C:13]([N:64]1[CH2:63][CH2:62][N:61]([C:44](=[O:43])[CH2:45][NH:46][C:47]([C:49]2[CH:54]=[CH:53][C:52]([C:55]3[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=3)=[CH:51][CH:50]=2)=[O:48])[CH2:66][CH2:65]1)=[O:15]
Reactant: O=C(O)c1cc(F)ccc1F
Reactant: O=C(NCC(=O)N1CCNCC1)c1ccc(-c2ccccc2)cc1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Solvent: O
Solvent: CCN(C(C)C)C(C)C
Product: O=C(NCC(=O)N1CCN(C(=O)c2cc(F)ccc2F)CC1)c1ccc(-c2ccccc2)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 46.5 %

Procedure:
DIPEA (149.8 mg, 1.15 mmol) was added to a stirred solution of 2,5-difluoro-benzoic acid (40.7 mg, 0.26 mmol) in DMF (3 mL), HOBt (38.2 mg, 0.28 mmol) and EDCI.HCl (123.4 mg, 0.64 mmol) at room temperature. After 2 minutes biphenyl-4-carboxylicacid (2-oxo-2-piperazin-1-yl-ethyl)-amide (100 mg, 0.31 mmol) was added and the resulting mixture was stirred at room temperature overnight. Cold water was then added, and the resulting precipitate was filtered. The residue was purified by column chromatography (using 60-120 mesh silica gel and 50% EtOAc in hexane as eluent) to afford 56 mg (46.9% yield) of biphenyl-4-carboxylicacid {2-[4-(2,5-difluoro-benzoyl)-piperazin-1-yl]-2-oxo-ethyl}-amide, LC-MS purity: 97.42%, 1H NMR: (CDCl3) δ 7.98-7.88 (d, 2H), 7.74-7.58 (dd, 4H), 7.54-7.34 (m, 3H), 7.2-7.08 (s, 3H), 4.4-4.26 (d, 2H), 3.94-3.78 (m, 3H), 3.76-3.56 (d, 3H), 3.54-3.38 (d, 3H).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([CH:8]=[C:9]([C:11]3[CH:12]=[CH:13][C:14]([C:18]([F:21])([F:20])[F:19])=[C:15]([CH:17]=3)[NH2:16])[N:10]=2)[CH:7]=1.C(#N)C.[CH3:25][C:26]([CH3:31])([CH3:30])[C:27](Cl)=[O:28]>N1C=CC=CC=1>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([CH:8]=[C:9]([C:11]3[CH:12]=[CH:13][C:14]([C:18]([F:21])([F:20])[F:19])=[C:15]([NH:16][C:27](=[O:28])[C:26]([CH3:31])([CH3:30])[CH3:25])[CH:17]=3)[N:10]=2)[CH:7]=1
Reactant: CC(C)(C)C(=O)Cl
Reactant: Nc1cc(-c2cn3cc(Br)ccc3n2)ccc1C(F)(F)F
Solvent: CC#N
Solvent: c1ccncc1
Product: CC(C)(C)C(=O)Nc1cc(-c2cn3cc(Br)ccc3n2)ccc1C(F)(F)F
Temperature: 80 °C
Reaction time: 0.33 h
Yield: 37 %

Procedure:
A 20 mL vial is charged with 5-(6-bromoimidazo[1,2-a]pyridin-2-yl)-2-(trifluoromethyl)aniline (0.463 g, 0.0013 mol), acetonitrile (7 mL) and pyridine (0.210 mL). The mixture is added trimethylacetyl chloride (0.320 mL, 2.6 mmol) and stirred for 20 min at 80° C. The solution is concentrated, taken into EtOAc (10 mL) and washed once with HCl (10 mL, 1M) and NaOH (10 mL, 1M). Organics are dried, concentrated, and purified on silica (0-100% EtOAc in Hexanes) to give the title compound (212 mg, 37% yield). LCMS m/z=440.4 [M+H]+, tR=2.67 min.
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][C:6]([CH2:9][CH2:10][CH:11](/[CH:21]=[CH:22]/[C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=2[O:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[CH2:12][CH2:13][CH2:14][CH2:15][C:16]([O:18][CH2:19][CH3:20])=[O:17])=[CH:5][CH:4]=1)#[N:2].C[Si]([N:45]=[N+:46]=[N-:47])(C)C.C([Sn](=O)CCCC)CCC>C1(C)C=CC=CC=1>[C:35]1([CH2:34][CH2:33][CH2:32][CH2:31][CH2:30][O:29][C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=2/[CH:22]=[CH:21]/[CH:11]([CH2:10][CH2:9][C:6]2[CH:7]=[CH:8][C:3]([C:1]3[NH:47][N:46]=[N:45][N:2]=3)=[CH:4][CH:5]=2)[CH2:12][CH2:13][CH2:14][CH2:15][C:16]([O:18][CH2:19][CH3:20])=[O:17])[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=1
Reactant: CCOC(=O)CCCCC(/C=C/c1ccccc1OCCCCCc1ccccc1)CCc1ccc(C#N)cc1
Reactant: C[Si](C)(C)N=[N+]=[N-]
Agent: CCCC[Sn](=O)CCCC
Solvent: Cc1ccccc1
Product: CCOC(=O)CCCCC(/C=C/c1ccccc1OCCCCCc1ccccc1)CCc1ccc(-c2nnn[nH]2)cc1
Temperature: 80 °C

Procedure:
A solution of 128 mg (0.24 mmol) of ethyl (7E)-6-[2-(4-cyanophenyl)ethyl]-8-{2-[(5-phenylpentyl)oxy]phenyl}oct-7-enoate in 10 ml of toluene is mixed with 0.47 ml (3.57 mmol) of trimethylsilyl azide and 88.9 mg (0.36 mmol) of di-n-butyltin oxide and heated at 80° C. for 12 hours. After cooling to room temperature, the mixture is washed with saturated sodium bicarbonate solution. The organic phase is separated off, washed with saturated sodium chloride solution and dried over sodium sulfate. After filtration, the filtrate is concentrated to dryness. The resulting crude product is purified by preparative HPLC. 62 mg (0.11 mmol, 44.8% of theory) of a colorless foam are obtained.
Reaction SMILES: [CH2:1]([C:8]1([N:15]([CH3:17])[CH3:16])[CH2:13][CH2:12][C:11](=[O:14])[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl-].[NH4+]>O1CCCC1.C([Mg]Cl)CC1C=CC=CC=1>[CH2:1]([C:8]1([N:15]([CH3:16])[CH3:17])[CH2:9][CH2:10][C:11]([CH2:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)([OH:14])[CH2:12][CH2:13]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CN(C)C1(Cc2ccccc2)CCC(=O)CC1
Agent: Cl[Mg]CCc1ccccc1
Agent: [Cl-]
Agent: [NH4+]
Solvent: C1CCOC1
Product: CN(C)C1(Cc2ccccc2)CCC(O)(CCc2ccccc2)CC1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
25.0 g 4-benzyl-4-dimethylaminocyclohexanone were dissolved in 150 ml analytical grade tetrahydrofuran, 151 ml 1.0 molar phenethylmagnesium chloride solution in THF were added under a nitrogen atmosphere, while cooling in an ice-bath, and the mixture was stirred overnight at room temperature. For working up, 150 ml ammonium chloride solution (20 per cent by weight) were added, while cooling with ice, the phases were separated, the aqueous phase was extracted three times with 80 ml diethyl ether each time, the combined organic phases were extracted three times with 70 ml dilute hydrochloric acid (5 per cent by weight) each time, the combined aqueous extracts were washed with 50 ml diethyl ether, adjusted to pH 9 with ammonia solution (25 per cent by weight) and extracted three times with 80 ml methylene chloride each time, the combined methylene chloride extracts were dried over sodium sulfate, filtered and concentrated and the residue was largely freed from solvent residues in vacuo. The crude product obtained (32.6 g) was chromatographed over silica gel with diethyl ether/hexane (v/v=1:1). 3.5 g of the nonpolar diastereoisomer of 4-benzyl-4-dimethylamino-1-phenethylcyclohexanol obtained were dissolved in 28 ml 2-butanone, 103 μl water followed by 1.44 ml trimethylchlorosilane were added at room temperature and the mixture was stirred over night at room temperature. The white solid which had precipitated out was filtered with suction, washed with diethyl ether and dried in an oil pump vacuum. 2.47 g of the hydrochloride of the nonpolar diastereoisomer of 4-benzyl-4-dimethylamino-1-phenethylcyclohexanol were obtained.
Reaction SMILES: C([O:3][C:4](=[O:47])[CH2:5][CH2:6][CH2:7][O:8][C:9]1[C:14]([C:15]2[CH:20]=[C:19]([CH3:21])[CH:18]=[C:17]([CH3:22])[CH:16]=2)=[CH:13][C:12]([C:23](=[O:38])[NH:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)=[CH:11][C:10]=1[C:39]1[CH:44]=[C:43]([CH3:45])[CH:42]=[C:41]([CH3:46])[CH:40]=1)C.[OH-].[K+]>CO.Cl.O>[CH3:22][C:17]1[CH:16]=[C:15]([C:14]2[CH:13]=[C:12]([C:23](=[O:38])[NH:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)[CH:11]=[C:10]([C:39]3[CH:44]=[C:43]([CH3:45])[CH:42]=[C:41]([CH3:46])[CH:40]=3)[C:9]=2[O:8][CH2:7][CH2:6][CH2:5][C:4]([OH:47])=[O:3])[CH:20]=[C:19]([CH3:21])[CH:18]=1
Reactant: CCOC(=O)CCCOc1c(-c2cc(C)cc(C)c2)cc(C(=O)NCCCCCCCc2ccccc2)cc1-c1cc(C)cc(C)c1
Agent: Cl
Agent: [K+]
Agent: [OH-]
Solvent: CO
Solvent: O
Product: Cc1cc(C)cc(-c2cc(C(=O)NCCCCCCCc3ccccc3)cc(-c3cc(C)cc(C)c3)c2OCCCC(=O)O)c1
Yield: 45.1 %

Procedure:
To a suspension of 4-[3,5,3″,5″-Tetramethyl-5′-(7-phenyl-heptylcarbamoyl)-[1,1′;3′,1″]terphenyl-2′-yloxy]-butyric acid ethyl ester (170 mg, 0.256 mmol) in 4 mL MeOH/1 mL H2O was added solid KOH (12 mg, 0.213 mmol). The reaction mixture was refluxed for 2 d and then the reaction mixture was diluted with 2N HCl and water. The aqueous solution was extracted with EtOAc (3×) and the combined organic extracts were dried over Na2SO4. The solvent was removed in vacuo to give an oil that was flash chromatographed (10% EtOAc:90% Hexanes) on silica gel to yield 70 mg, 43% of the acid as an oily white foam. mp 64-66° C.; 1H NMR (DMSO-d6) δ 1.29-1.30 (m, 6H); 1.32-1.39 (m, 2H); 1.46-1.48 (m, 4H); 1.86 (t, J=7.47 Hz, 2H); 2.33 (s, 12H); 2.53 (t, J=7.58 Hz, 2H); 3.19-3.31 (m, 4H); 7.01 (s, 2H); 7.12-7.16 (m, 3H); 7.17-7.19 (m, 4H); 7.21-7.24 (m, 2H) 7.71 (s, 2H); 8.48 (t, J=7.00 Hz, 1H); 11.86 (s, 1H); IR 3325, 2925, 2875, 1710, 1630, 1600, 1535, 1450, 1290, 1225, 1210, 850, and 700 cm−1; mass spectrum [(+)APCI], m/z 606 [M+H]+; Anal Calcd. for C40H47NO4: C, 79.30; H, 7.82; N, 2.31; Found: C, 78.65; H, 7.86; N, 1.87.
Reaction SMILES: Br[C:2]1[CH:24]=[C:23]([Cl:25])[C:5]([C:6]([C:8]2[C:16]3[C:11](=[C:12]([NH:17][C:18]([CH:20]4[CH2:22][CH2:21]4)=[O:19])[N:13]=[CH:14][CH:15]=3)[NH:10][CH:9]=2)=[O:7])=[C:4]([Cl:26])[CH:3]=1.[CH3:27][C:28]1[C:32](B(O)O)=[C:31]([CH3:36])[O:30][N:29]=1.O1CCOCC1.C(=O)([O-])[O-].[K+].[K+]>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].O>[Cl:25][C:23]1[CH:24]=[C:2]([C:32]2[C:28]([CH3:27])=[N:29][O:30][C:31]=2[CH3:36])[CH:3]=[C:4]([Cl:26])[C:5]=1[C:6]([C:8]1[C:16]2[C:11](=[C:12]([NH:17][C:18]([CH:20]3[CH2:22][CH2:21]3)=[O:19])[N:13]=[CH:14][CH:15]=2)[NH:10][CH:9]=1)=[O:7]
Reactant: O=C(c1c(Cl)cc(Br)cc1Cl)c1c[nH]c2c(NC(=O)C3CC3)nccc12
Reactant: Cc1noc(C)c1B(O)O
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: O=C([O-])[O-]
Solvent: O
Solvent: C1COCCO1
Product: Cc1noc(C)c1-c1cc(Cl)c(C(=O)c2c[nH]c3c(NC(=O)C4CC4)nccc23)c(Cl)c1
Temperature: 90 °C
Reaction time: 0.08 h
Yield: 16 %

Procedure:
A mixture of N-[3-(4-bromo-2,6-dichlorobenzoyl)-1H-pyrrolo[2,3-c]pyridin-7-yl]cyclopropanecarboxamide (0.1 g, 0.2 mmol) and (3,5-dimethyl-1,2-oxazol-4-yl)boronic acid (0.037 g, 0.26 mmol) was taken in a vial. To the reaction mixture, 1,4dioxane (3 mL), potassium carbonate (0.091 g, 0.6 mmol) and water (0.5 mL) were added. The whole reaction mixture was stirred with argon gas for about five minutes. Finally dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II) (0.018 g, 0.02 mmol) was added to the reaction mixture, the vial was sealed properly and heated at 90° C. for about 4 hours. The reaction mixture was cooled to room temperature, followed by addition of water (25 mL), extracted with ethyl acetate (2×50 mL). The organic layer was dried over anhydrous sodium sulphate and concentrated under vacuum to get the crude. The crude was purified by preparative thin layer chloromatography using methanol (6%) in dichloromethane to obtain N-{3-[2,6-dichloro-4-(3,5-dimethyl-1,2-oxazol-4-yl)benzoyl]-1H-pyrrolo[2,3-c]pyridin-7-yl}cyclopropanecarboxamide (0.015 g, 15%).
Reaction SMILES: OS(O)(=O)=O.[NH2:6][C:7]1[CH:8]=[C:9]([CH:13]=[CH:14][C:15]=1[O:16][CH3:17])[C:10]([OH:12])=[O:11].[CH3:18]O>>[CH3:18][O:11][C:10](=[O:12])[C:9]1[CH:13]=[CH:14][C:15]([O:16][CH3:17])=[C:7]([NH2:6])[CH:8]=1
Reactant: CO
Reactant: COc1ccc(C(=O)O)cc1N
Agent: O=S(=O)(O)O
Product: COC(=O)c1ccc(OC)c(N)c1
Temperature: 25 °C

Procedure:
Concentrated H2SO4 (9 mL) was added in portions to a stirred solution of 3-amino-4-methoxybenzoic acid (20.06 g, 110.4 mmol) in methanol (280 mL). The mixture was heated to reflux overnight then cooled to room temperature, and the solvent was removed in vacuo. The residue was shaken with 10% aqueous potassium carbonate then extracted with ethyl acetate three times. The combined extracts were washed with saturated sodium bicarbonate, dried (MgSO4), filtered, and stripped of solvent under reduced pressure. The residual solid was triturated with hexane and filtered to yield the product (10.82 g); m.p. 75-77° C.
Reaction SMILES: C[Si]([C:5]#[C:6][C:7]1[CH:12]=[CH:11][C:10]([Si:13]([C:28]2[CH:33]=[CH:32][C:31]([C:34]#[C:35][Si](C)(C)C)=[CH:30][CH:29]=2)([CH3:27])[O:14][Si:15]([CH3:26])([CH3:25])[O:16][Si:17]([CH3:24])([CH3:23])[O:18][Si:19]([CH3:22])([CH3:21])[CH3:20])=[CH:9][CH:8]=1)(C)C.CO.C1COCC1>CO.C1COCC1.N.O>[C:6]([C:7]1[CH:8]=[CH:9][C:10]([Si:13]([C:28]2[CH:29]=[CH:30][C:31]([C:34]#[CH:35])=[CH:32][CH:33]=2)([CH3:27])[O:14][Si:15]([CH3:26])([CH3:25])[O:16][Si:17]([CH3:23])([CH3:24])[O:18][Si:19]([CH3:20])([CH3:21])[CH3:22])=[CH:11][CH:12]=1)#[CH:5]
Reactant: C[Si](C)(C)C#Cc1ccc([Si](C)(O[Si](C)(C)O[Si](C)(C)O[Si](C)(C)C)c2ccc(C#C[Si](C)(C)C)cc2)cc1
Agent: N
Solvent: C1CCOC1
Solvent: O
Solvent: CO
Product: C#Cc1ccc([Si](C)(O[Si](C)(C)O[Si](C)(C)O[Si](C)(C)C)c2ccc(C#C)cc2)cc1
Reaction time: 24 h
Yield: 61 %

Procedure:
Tetramethylsilane (TMS) was deprotonated through a reaction with an ammonia solution to produce the target monomer bis-(4-ethynylphenyl)-octamethyltetrasiloxane. Specifically, 1.00 g bis-(4-trimethylsilylethynylphenyl)-octamethyltetrasiloxane in MeOH/THF/NH3—H2O mixture (generally 1:1:1, but sometimes it is necessary to adjust MeOH/THF ratio to obtain transparent reaction mixture) was placed in a round-bottomed flask equipped with a magnetic stirring bar. The flask was placed in an ice-water bath and stirred for 24 h (monitored by TLC). Then, the reaction was stopped, and the mixture was extracted via DCM and water. After removing the solvent of the organic layer, Bis-(4-ethynylphenyl)-octamethyltetrasiloxane was obtained in a 61% yield as a light yellow liquid by running silica column with hexane/DCM (10:1) as eluent.
Reaction SMILES: [CH2:1]([O:8][C:9]([N:11]1[CH2:27][CH2:26][C:15]2[C:16]3[CH:17]([OH:25])[C:18]([F:24])([F:23])[CH2:19][C:20]=3[CH:21]=[CH:22][C:14]=2[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[BH4-].[Na+].[CH3:30]I>C1COCC1.O>[CH2:1]([O:8][C:9]([N:11]1[CH2:27][CH2:26][C:15]2[C:16]3[CH:17]([O:25][CH3:30])[C:18]([F:23])([F:24])[CH2:19][C:20]=3[CH:21]=[CH:22][C:14]=2[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=C(OCc1ccccc1)N1CCc2ccc3c(c2CC1)C(O)C(F)(F)C3
Reactant: CI
Agent: [BH4-]
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Product: COC1c2c(ccc3c2CCN(C(=O)OCc2ccccc2)CC3)CC1(F)F
Reaction time: 0.17 h
Yield: 73.7 %

Procedure:
To a stirred solution of the product from step (c) (0.13 g, 0.35 mmol) dissolved in THF (2 ml) at 0° C. was added NaH (0.046, 0.86 mmol). The reaction mixture was allowed to stir for 10 minutes followed by the addition of methyl iodide (0.053 mL, 0.86 mmol). The reaction mixture was stirred at RT for 24 hours. The reaction mixture was diluted with water and extracted with ethyl acetate (3×). The combined ethyl acetate extracts were washed with brine, dried (Na2SO4), and solvent evaporated in vacuo to give the sub-titled compound as a yellow oil (0.10 g). MS: ESI (positive): 388 (M+H).
Reaction SMILES: Cl.[N:2]1([NH:11][C:12](=[NH:15])SC)[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3]1.Cl.[NH2:17][OH:18].[O-]CC.[K+]>C(O)C>[OH:18][NH:17][C:12]([NH:11][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3]1)=[NH:15]
Reactant: NO
Reactant: CSC(=N)NN1CCc2ccccc21
Agent: CC[O-]
Agent: Cl
Agent: [K+]
Solvent: CCO
Product: N=C(NO)NN1CCc2ccccc21

Procedure:
10 g of 1-(indolin-1-yl)-2-methylisothiourea hydrochloride and 11.4 g of hydroxylamine hydrochloride were suspended in 240 ml of ethanol and were heated to the boil for one hour upon the addition of 6.9 g of potassium ethoxide. Upon cooling, the potassium chloride and the excess hydroxylamine hydrochloride were filtered off with suction and the filtrate was evaporated to dryness. The evaporation residue was partitioned between concentrated aqueous ammonia solution and methylene choride. The methylene chloride solution was dried over magnesium sulphate and evaporated to dryness. 1-hydroxy-3-(indolin-1-yl)guanidine was obtained as an evaporation residue and was crystallized upon the addition of acetic acid, as the acetate from ethanol/ether having a M.Pt. of 155° - 156°.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[C:7]([C:12]([OH:14])=O)[CH:6]=[CH:5]2.[NH3:15]>S(Cl)(Cl)=O>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[C:7]([C:12]([NH2:15])=[O:14])[CH:6]=[CH:5]2
Reactant: N
Reactant: O=C(O)c1ccc2cc(Br)ccc2c1
Solvent: O=S(Cl)Cl
Product: NC(=O)c1ccc2cc(Br)ccc2c1
Temperature: 25 °C
Reaction time: 3 h
Yield: 90.4 %

Procedure:
6-bromo-2-naphthoic acid (2 g, 7.97 mmol) was stirred in thionyl chloride (13.28 ml) at 70° C. for 16 h. Solvent was evaporated, and the residue was dissolved in CH2Cl2 and concentrated again. To the acid chloride intermediate was added ammonia (7N in MeOH, 13.66 ml, 96 mmol) and the mixture was stirred at room temperature for 3 h. The reaction mixture was concentrated, diluted in ethyl acetate and filtered. The solid was rinsed with ethyl acetate and then dried. The title compound 2a (1.802 g, 90%) was isolated as beige solid. LC-MS (M+1) 251.9, t=1.34 min.
Reaction SMILES: [C:1]1([S:7]([N:10]2[C:14]3=[N:15][CH:16]=[C:17]([N+:20]([O-:22])=[O:21])[C:18](Cl)=[C:13]3[CH:12]=[CH:11]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:23]([O:27][C:28]([N:30]1[CH2:36][CH2:35][CH2:34][CH2:33][CH:32]([NH2:37])[CH2:31]1)=[O:29])([CH3:26])([CH3:25])[CH3:24].C(N(C(C)C)CC)(C)C>CC(O)C>[C:23]([O:27][C:28]([N:30]1[CH2:36][CH2:35][CH2:34][CH2:33][CH:32]([NH:37][C:18]2[C:17]([N+:20]([O-:22])=[O:21])=[CH:16][N:15]=[C:14]3[N:10]([S:7]([C:1]4[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=4)(=[O:9])=[O:8])[CH:11]=[CH:12][C:13]=23)[CH2:31]1)=[O:29])([CH3:26])([CH3:24])[CH3:25]
Reactant: O=[N+]([O-])c1cnc2c(ccn2S(=O)(=O)c2ccccc2)c1Cl
Reactant: CC(C)(C)OC(=O)N1CCCCC(N)C1
Solvent: CC(C)O
Solvent: CCN(C(C)C)C(C)C
Product: CC(C)(C)OC(=O)N1CCCCC(Nc2c([N+](=O)[O-])cnc3c2ccn3S(=O)(=O)c2ccccc2)C1
Temperature: 120 °C
Yield: 83.2 %

Procedure:
A mixture of 1-benzenesulfonyl-4-chloro-5-nitro-1H-pyrrolo[2,3-b]pyridine (0.6981 g, 2.067 mmol), 3-Amino-azepane-1-carboxylic acid tert-butyl ester (0.4752 g, 2.217 mmol), and diisopropylethylamine (0.50 mL, 2.9 mmol) in propan-2-ol (12 mL) was heated in a microwave reactor at 120° C. for 20 minutes. The solvent was evaporated in vacuo and then purified by column chromatography on silica gel (gradient: 0 to 30% ethyl acetate in heptanes) affording 0.8869 g (83%) of 3-(1-Benzenesulfonyl-5-nitro-1H-pyrrolo[2,3-b]pyridin-4-ylamino)-azepane-1-carboxylic acid tert-butyl ester. LCMS (Method E, ESI): RT=2.07 min, m+H=516.2.
Reaction SMILES: C(O)C(N)(CO)CO.Cl.[Mg+2].[Cl-].[Cl-].[CH3:13][CH2:14][CH2:15][CH2:16][CH2:17][C@H:18]([OH:37])/[CH:19]=[CH:20]/[C@H:21]1[C:25](=[O:26])[CH2:24][C@H:23]([OH:27])[C@@H:22]1[CH2:28]/[CH:29]=[CH:30]/[CH2:31][CH2:32][CH2:33][C:34]([OH:36])=[O:35]>>[CH3:13][CH2:14][CH2:15][CH2:16][CH2:17][C@H:18]([OH:37])/[CH:19]=[CH:20]/[C@H:21]1[C:25](=[O:26])[CH2:24][C@H:23]([OH:27])[C@@H:22]1[CH2:28]/[CH:29]=[CH:30]\[CH2:31][CH2:32][CH2:33][C:34]([OH:36])=[O:35]
Reactant: CCCCC[C@H](O)/C=C/[C@H]1C(=O)C[C@H](O)[C@@H]1C/C=C/CCCC(=O)O
Agent: Cl
Agent: NC(CO)(CO)CO
Agent: [Cl-]
Product: CCCCC[C@H](O)/C=C/[C@H]1C(=O)C[C@H](O)[C@@H]1C/C=C\CCCC(=O)O

Procedure:
To a binding-reaction solution (50 mM Tris/HCl, pH 7.4, 5 mM MgCl2) (0.2 ml) were added human platelet membrane fraction (0.1 mg) and 5 nM [3H]PGD2 (115 Ci/mmol), and reacted at 4° C. for 90 min. After the reaction completed, the reaction mixture was filtered through the glass fiber filter paper, washed several times with cooled saline, and measured radioactivity retained on the filter paper. The specific binding was calculated by subtracting the non-specific binding (the binding in the presence of 10 μM PGD2) from the total binding. The binding-inhibitory activity of each compound was expressed as concentration required for 50% inhibition (IC50), which was determined by depicting a substitution curve by plotting the binding ratio (%) in the presence of each compound, where the binding ratio in the absence of a test compound is 100%. The results are shown in Table below.