Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH:1][C:2]1[CH:10]=[CH:9][C:8]([C:11]2[N:12]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[C:13]3[C:18]([CH:19]=2)=[CH:17][C:16]([CH2:20][N:21]2[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]2)=[CH:15][CH:14]=3)=[C:7]2[C:3]=1[CH2:4][NH:5][C:6]2=[O:34].C(N(CC)CC)C.[C:42]1([CH2:48][S:49](Cl)(=[O:51])=[O:50])[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1>ClCCl>[C:42]1([CH2:48][S:49]([O:1][C:2]2[CH:10]=[CH:9][C:8]([C:11]3[N:12]([C:27]([O:29][C:30]([CH3:31])([CH3:33])[CH3:32])=[O:28])[C:13]4[C:18]([CH:19]=3)=[CH:17][C:16]([CH2:20][N:21]3[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]3)=[CH:15][CH:14]=4)=[C:7]3[C:3]=2[CH2:4][NH:5][C:6]3=[O:34])(=[O:51])=[O:50])[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1
Reactant: O=S(=O)(Cl)Cc1ccccc1
Reactant: CC(C)(C)OC(=O)n1c(-c2ccc(O)c3c2C(=O)NC3)cc2cc(CN3CCCCC3)ccc21
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(C)(C)OC(=O)n1c(-c2ccc(OS(=O)(=O)Cc3ccccc3)c3c2C(=O)NC3)cc2cc(CN3CCCCC3)ccc21
Yield: 37 %

Procedure:
In a similar manner to Step 1 of Example 227, 4-hydroxy-7-[1-(tert-butoxycarbonyl)-5-(piperidinomethyl)indol-2-yl]isoindolinone (0.184 g, 0.399 mmol) was dissolved in dichloromethane (3.6 mL), and the solution was treated with triethylamine (0.250 mL, 1.79 mmol) and a-toluenesulfonyl chloride (0.152 g, 0.797 mmol), followed by purification by flash column chromatography (chloroform/methanol=85/15) to obtain 4-(a-toluenesulfonyloxy)-7-[1-(tert-butoxycarbonyl)-5-(piperidinomethyl)indol-2-yl]isoindolinone (0.0908 g, yield 37%).
Reaction SMILES: [Cl:1][C:2]1[CH:28]=[CH:27][C:5]([CH2:6][N:7]2[C:15]3[C:10](=[CH:11][C:12]([CH:16]=[C:17]4[S:21][C:20](SCCC)=[N:19][C:18]4=[O:26])=[CH:13][CH:14]=3)[CH:9]=[N:8]2)=[C:4]([C:29]([F:32])([F:31])[F:30])[CH:3]=1.[CH3:33][C:34]1[N:38]([CH:39]2[CH2:44][CH2:43][NH:42][CH2:41][CH2:40]2)[C:37]([CH3:45])=[N:36][N:35]=1>>[Cl:1][C:2]1[CH:28]=[CH:27][C:5]([CH2:6][N:7]2[C:15]3[C:10](=[CH:11][C:12]([CH:16]=[C:17]4[S:21][C:20]([N:42]5[CH2:41][CH2:40][CH:39]([N:38]6[C:34]([CH3:33])=[N:35][N:36]=[C:37]6[CH3:45])[CH2:44][CH2:43]5)=[N:19][C:18]4=[O:26])=[CH:13][CH:14]=3)[CH:9]=[N:8]2)=[C:4]([C:29]([F:30])([F:31])[F:32])[CH:3]=1
Reactant: Cc1nnc(C)n1C1CCNCC1
Reactant: CCCSC1=NC(=O)C(=Cc2ccc3c(cnn3Cc3ccc(Cl)cc3C(F)(F)F)c2)S1
Product: Cc1nnc(C)n1C1CCN(C2=NC(=O)C(=Cc3ccc4c(cnn4Cc4ccc(Cl)cc4C(F)(F)F)c3)S2)CC1

Procedure:
5-[1-(4-Chloro-2-trifluoromethyl-benzyl)-1H-indazol-5-ylmethylene]-2-[4-(3,5-dimethyl-[1,2,4]triazol-4-yl)-piperidin-1-yl]-thiazol-4-one was prepared from 5-[1-(4-Chloro-2-trifluoromethyl-benzyl)-1H-indazol-5-ylmethylene]-2-propylsulfanyl-thiazol-4-one and 4-(3,5-Dimethyl-[1,2,4]triazol-4-yl)piperidine following General Procedure B.
Reaction SMILES: [C:1]([CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][NH:9][C:10](=[S:13])SC)([OH:3])=[O:2].[N-:14]=[N+:15]=[N-:16].[Na+].[OH-].[Na+]>>[C:1]([CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][N:9]1[C:10]([SH:13])=[N:16][N:15]=[N:14]1)([OH:3])=[O:2]
Reactant: CSC(=S)NCCCCCC(=O)O
Reactant: [N-]=[N+]=[N-]
Agent: [Na+]
Agent: [OH-]
Product: O=C(O)CCCCCn1nnnc1S

Procedure:
Reaction of methyl 5-carboxypentyldithiocarbamate with sodium azide and sodium hyroxide as described in Example 7 gave 1-(5-carboxypentyl)tetrazole-5-thiol, m.p. 100°-100.5°.
Reaction SMILES: [NH2:1][C:2]1[C:3]2[C:8]([N:9]=[C:10]3[C:15]=1[C:14](=[O:16])[CH2:13][CH2:12][CH2:11]3)=[CH:7][CH:6]=[CH:5][CH:4]=2.[CH3:17][Li]>O1CCCC1.CCOCC>[NH2:1][C:2]1[C:3]2[C:8]([N:9]=[C:10]3[C:15]=1[C:14]([CH3:17])([OH:16])[CH2:13][CH2:12][CH2:11]3)=[CH:7][CH:6]=[CH:5][CH:4]=2
Reactant: [Li]C
Reactant: Nc1c2c(nc3ccccc13)CCCC2=O
Solvent: CCOCC
Solvent: C1CCOC1
Product: CC1(O)CCCc2nc3ccccc3c(N)c21
Temperature: 25 °C
Reaction time: 8 h

Procedure:
In 100 ml of dry tetrahydrofuran was suspended 5.00 g of 9-amino-3,4-dihydroacridin-1(2H)-one at ice temperature and 78 ml (4 eq) of 1.2M CH3Li solution in ether was added thereto at such a rate as to avoid bubbling. The reaction mixture was stirred overnight as it warmed to ambient temperature. The next day 20 ml more of the CH3Li solution was added to drive the reaction to a completion. After 0.5 hour the reaction was quenched with excess water and 4.97 g of the precipitate was collected and air dried. The product was recrystallized from MeOH/toluene. The yield was 2.06 g (38%) of granules, melting point 250° C.
Reaction SMILES: [C:1]([O:5][C:6](=[O:36])[NH:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[C:27](=[N:28][OH:29])[C:26]4[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=4)[O:20][C:19]=3[C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[C:37](=O)([O-])[O-].[K+].[K+].IC.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C>[C:1]([O:5][C:6](=[O:36])[NH:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[C:27](=[N:28][O:29][CH3:37])[C:26]4[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=4)[O:20][C:19]=3[C:30]3[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=3)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:2])[CH3:3]
Reactant: O=C([O-])[O-]
Reactant: CC(C)(C)OC(=O)NC1(c2ccc(-c3c(-c4ccccc4)oc4ccccc4c3=NO)cc2)CCC1
Agent: [Cs+]
Agent: [K+]
Solvent: CI
Solvent: CN(C)C=O
Product: CON=c1c(-c2ccc(C3(NC(=O)OC(C)(C)C)CCC3)cc2)c(-c2ccccc2)oc2ccccc12
Reaction time: 2 h
Yield: 90.3 %

Procedure:
To a stirred solution of {1-[4-(4-hydroxyimino-2-phenyl-4H-chromen-3-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl ester (27 mg, 0.056 mmol) in DMF (2 mL) was added potassium carbonate (15.5 mg, 0.112 mmol) and iodomethane (0.011 mL, 0.168 mmol) at RT. After 2 hours, cesium carbonate (36.5 mg, 0.112 mmol) and iodomethane (0.021 mL, 0.336 mmol) were added and the mixture stirred for a further 1.5 hours. The reaction mixture was partitioned between EtOAc and water. The aqueous phase was isolated and extracted with EtOAc. The combined organic extracts were washed with water and brine, dried (Na2SO4), filtered, and concentrated in vacuo. The resultant residue was subjected to flash chromatography (SiO2, gradient 15 to 25% EtOAc in cyclohexane) to afford the title compound (25.1 mg, 90%) as a colourless gum. LCMS (Method A): RT=5.20 min, [M+H]+=497.
Reaction SMILES: [Si:1]([O:8][CH2:9][CH:10]([N:19]1[CH:24]=[CH:23][C:22]([C:25]2[CH:30]=[CH:29][N:28]=[C:27](S(C)(=O)=O)[N:26]=2)=[CH:21][C:20]1=[O:35])[C:11]1[CH:16]=[CH:15][C:14]([Cl:17])=[C:13]([F:18])[CH:12]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[NH2:36][CH:37]1[CH2:42][CH:41]2[CH2:43][CH:38]1[C:39](=[O:44])[O:40]2.Cl>C(O)(CC)C>[Si:1]([O:8][CH2:9][C@@H:10]([N:19]1[CH:24]=[CH:23][C:22]([C:25]2[CH:30]=[CH:29][N:28]=[C:27]([NH:36][CH:37]3[CH2:42][CH:41]4[CH2:43][CH:38]3[C:39](=[O:44])[O:40]4)[N:26]=2)=[CH:21][C:20]1=[O:35])[C:11]1[CH:16]=[CH:15][C:14]([Cl:17])=[C:13]([F:18])[CH:12]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]
Reactant: NC1CC2CC1C(=O)O2
Reactant: CC(C)(C)[Si](C)(C)OCC(c1ccc(Cl)c(F)c1)n1ccc(-c2ccnc(S(C)(=O)=O)n2)cc1=O
Agent: Cl
Solvent: CCC(C)O
Product: CC(C)(C)[Si](C)(C)OC[C@H](c1ccc(Cl)c(F)c1)n1ccc(-c2ccnc(NC3CC4CC3C(=O)O4)n2)cc1=O
Temperature: 130 °C
Reaction time: 3 h
Yield: 100.1 %

Procedure:
A microwave vial was charged with 1-(2-(tert-butyldimethylsilyloxy)-1-(4-chloro-3-fluorophenyl)ethyl)-4-(2-(methylsulfonyl)pyrimidin-4-yl)pyridin-2(1H)-one (150 mg, 0.280 mmol), 5-amino-2-oxa-bicyclo[2.2.1]heptan-3-one (89 mg, 0.70 mmol), a drop of concentrated HCl, and s-butanol (2.0 mL). The mixture was stirred at 130° C. under microwave irradiation for 3 hours. After completion of the reaction, the mixture was concentrated to give 1-((S)-2-(tert-butyldimethylsilyloxy)-1-(4-chloro-3-fluorophenyl)ethyl)-4-(2-(3-oxo-2-oxa-bicyclo[2.2.1]heptan-5-ylamino)pyrimidin-4-yl)pyridin-2(1H)-one (164 mg, 100% yield), which was used in the next step without further purification. LCMS (ESI) m/z: 285.2 [M+H]+.
Reaction SMILES: [C:1]1([CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][OH:15])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[N+](N[C:20]1[NH:25][C:24](=[O:26])[C:23]([CH2:27][C:28]2[CH:29]=[N:30][CH:31]=[CH:32][CH:33]=2)=[CH:22][N:21]=1)([O-])=O>N1C=CC=CC=1>[C:1]1([CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][O:15][C:20]2[NH:25][C:24](=[O:26])[C:23]([CH2:27][C:28]3[CH:29]=[N:30][CH:31]=[CH:32][CH:33]=3)=[CH:22][N:21]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: OCCCCCCCCc1ccccc1
Reactant: O=c1[nH]c(N[N+](=O)[O-])ncc1Cc1cccnc1
Solvent: c1ccncc1
Product: O=c1[nH]c(OCCCCCCCCc2ccccc2)ncc1Cc1cccnc1

Procedure:
A mixture of 8-phenyl-1-octanol (1.5 g), 2-nitroamino-5-(pyrid-3-ylmethyl)pyrimidin-4-one (1.0 g) and pyridine (5 ml) was stirred at reflux for 24 hours, then the pyridine was removed by evaporation. Water was added, and the product extracted into dichloromethane, which was dried and evaporated. The residue was purified by chromatography (silica, 0-5% methanol in dichloromethane) and recrystallisation from ether to give 2-(8-phenyloct-1-yl)oxy-5-(pyrid-3-ylmethyl)pyrimidin-4-one as a pale buff solid (0.1 g). MPt 53-55° C.; 1H-NMR (CDCl3) δ 1.32 (8H, m), 1.60 (2H, m), 1.74 (2H, m), 2.58 (2H, t), 3.72 (2H, t), 4.31 (2H, t), 7.1-7.3 (6H, m), 7.54 (1H, m), 7.63 (1H, m), 8.45 (1H, m) and 8.55 (1H, d); MS (EI) Found M=391; C24H29N3O2 requires 391.
Reaction SMILES: [O:1]=[C:2]1[NH:19][C:18]2[CH:20]=[CH:21][CH:22]=[CH:23][C:17]=2[C:4]2([CH2:9][CH2:8][N:7](C(OC(C)(C)C)=O)[CH2:6][CH2:5]2)[O:3]1.FC(F)(F)C(O)=O>ClCCl>[NH:7]1[CH2:6][CH2:5][C:4]2([O:3][C:2](=[O:1])[NH:19][C:18]3[CH:20]=[CH:21][CH:22]=[CH:23][C:17]2=3)[CH2:9][CH2:8]1
Reactant: CC(C)(C)OC(=O)N1CCC2(CC1)OC(=O)Nc1ccccc12
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: O=C1Nc2ccccc2C2(CCNCC2)O1
Temperature: 25 °C
Reaction time: 0.75 h
Yield: 66.7 %

Procedure:
tert-Butyl 2-oxo-1,2-dihydrospiro[benzo[d][1,3]oxazine-4,4′-piperidine]-1′-carboxylate (6.71 g, 21.1 mmol) was dissolved in dichloromethane (50 mL), treated with trifluoroacetic acid (20 mL) and stirred at room temperature for 45 min. The reaction was concentrated under reduced pressure, re-dissolved in acetonitrile and re-concentrated under reduced pressure. The crude TFA salt was cooled in an ice-H2O bath, dissolved in ice-cold saturated brine (20 mL) and H2O (50 mL) and basified with ice-cold 35% NaOH (aq). A small amount of product (obtained from extraction with 50 mL ethyl acetate) was added to the aqueous layer to initiate crystallization. The suspension obtained was cooled in an ice-H2O bath, filtered, rinsed with ice-cold H2O and dried to afford 3.071 g spiro[benzo[d][1,3]oxazine-4,4′-piperidin]-2(1H)-one free base as a white crystalline solid. An additional 800 mg free base was obtained via extraction of the mother liquor with ethyl acetate (10×50 mL) and subsequent trituration of the crude free base with acetonitrile (overall yield=84%). LC/MS m/z 219.2 [M+H]+, retention time 0.58 min (RP—C18, 10-99% CH3CN/0.05% TFA); 1H-NMR (400 MHz, DMSO-d6) δ 10.17 (br s, 1H), 7.23 (m, 2H), 7.02 (m, 1H), 6.87 (dd, J=8.2, 1.2 Hz, 1H), 2.89 (m, 2H), 2.82 (m, 2H), 1.84 (m, 4H).
Reaction SMILES: [OH:1][C:2]1[CH:9]=[CH:8][C:7]([C:10]2[O:14][N:13]=[C:12]([C:15]3[CH:23]=[CH:22][CH:21]=[C:20]4[C:16]=3[CH2:17][CH2:18][CH:19]4[NH:24][CH2:25][CH2:26][OH:27])[N:11]=2)=[CH:6][C:3]=1[C:4]#[N:5].C([O-])([O-])=O.[K+].[K+].Br[CH2:35][CH:36]([CH3:38])[CH3:37]>CC(N(C)C)=O>[OH:27][CH2:26][CH2:25][NH:24][CH:19]1[C:20]2[C:16](=[C:15]([C:12]3[N:11]=[C:10]([C:7]4[CH:8]=[CH:9][C:2]([O:1][CH2:35][CH:36]([CH3:38])[CH3:37])=[C:3]([CH:6]=4)[C:4]#[N:5])[O:14][N:13]=3)[CH:23]=[CH:22][CH:21]=2)[CH2:17][CH2:18]1
Reactant: N#Cc1cc(-c2nc(-c3cccc4c3CCC4NCCO)no2)ccc1O
Reactant: CC(C)CBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(=O)N(C)C
Product: CC(C)COc1ccc(-c2nc(-c3cccc4c3CCC4NCCO)no2)cc1C#N
Temperature: 75 °C
Reaction time: 6 h
Yield: 36.8 %

Procedure:
Prepared using General Procedure 11. To a solution of 2-hydroxy-5-(3-(1-(2-hydroxyethylamino)-2,3-dihydro-1H-inden-4-yl)-1,2,4-oxadiazol-5-yl)benzonitrile 102 (15.0 mg, 0.041 mmol) in DMA (2 mL) was added K2CO3 (16.9 mg, 0.12 mmol) and 1-bromo-2-methylpropane (11.3 mg, 0.08 mmol). The mixture was stirred 6 h at 75° C. The solvent was evaporated and the mixture was partitioned between EA and brine. The organic layer was dried over MgSO4, filtered, and the solvent evaporated. The final compound was purified by preparative HPLC to give 6.31 mg (37%) of 5-(3-(1-((2-hydroxyethyl)amino)-2,3-dihydro-1H-inden-4-yl)-1,2,4-oxadiazol-5-yl)-2-isobutoxybenzonitrile 103 as a white solid. LCMS-ESI (m/z) calculated for C24H16N4O3: 418.5. found 419.2 [M+H]+, tR=2.61 min.
Reaction SMILES: [C:1](Cl)(=[O:3])[CH3:2].Cl.[NH2:6][C@H:7]1[CH2:11][N:10]([C:12]([CH3:15])([CH3:14])[CH3:13])[C@H:9]([C:16]([NH:18][CH2:19][C@@H:20]([OH:48])[C@@H:21]([NH:29][C:30](=[O:47])[C@H:31]([CH2:43][C:44](=[O:46])[NH2:45])[NH:32][C:33]([O:35][CH2:36][C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)=[O:34])[CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[O:17])[CH2:8]1.C(=O)(O)[O-].[Na+]>O.CN(C)C=O>[C:1]([NH:6][C@H:7]1[CH2:11][N:10]([C:12]([CH3:14])([CH3:13])[CH3:15])[C@H:9]([C:16]([NH:18][CH2:19][C@@H:20]([OH:48])[C@@H:21]([NH:29][C:30](=[O:47])[C@H:31]([CH2:43][C:44](=[O:46])[NH2:45])[NH:32][C:33]([O:35][CH2:36][C:37]2[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=2)=[O:34])[CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[O:17])[CH2:8]1)(=[O:3])[CH3:2]
Reactant: CC(=O)Cl
Reactant: CC(C)(C)N1C[C@H](N)C[C@H]1C(=O)NC[C@@H](O)[C@H](Cc1ccccc1)NC(=O)[C@H](CC(N)=O)NC(=O)OCc1ccccc1
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: CC(=O)N[C@@H]1C[C@@H](C(=O)NC[C@@H](O)[C@H](Cc2ccccc2)NC(=O)[C@H](CC(N)=O)NC(=O)OCc2ccccc2)N(C(C)(C)C)C1
Temperature: 0 °C
Reaction time: 5 h

Procedure:
15 mg of freshly distilled acetyl chloride were added to a solution, which was cooled to 0° C. and stirred, of 12 mg of 4(R)-amino-N2 -[3(S)-[[N-(benzyloxycarbonyl)-L-asparaginyl]amino]-2(R)-hydroxy-4-phenylbutyl]-N1 -tert.butyl-L-prolinamide hydrochloride and 21 mg of sodium bicarbonate in 0.5 ml of water and 0.25 ml of dimethylformamide. The mixture was stirred vigorously at 0° C. for 5 hours and then left to stand at room temperature overnight. The mixture was diluted with waterand extracted with dichloromethane. The combined dichloromethane extracts were evaporated to give a gum which was purified by flash chromatography on silica gel using 20% methanol in dichloromethane for the elution. Therewere obtained 2 mg of 4(R)-acetylamino-N2 -[3(S)-[[N-(benzyloxycarbonyl)-L-asparaginyl]amino]-2(R)-hydroxy-4-phenylbutyl]-N1 -tert.butyl-L-prolinamide as a semi-solid; MS: m/e 639 [M+H]+.
Reaction SMILES: [C:1]1([PH:7][C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH2:14]=[CH:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH:26]=[CH2:27]>>[CH2:27]([P:7]([C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1)[C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1)[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22][CH2:21][CH2:20][CH2:19][CH2:18][CH2:17][CH2:16][CH:15]=[CH2:14]
Reactant: c1ccc(Pc2ccccc2)cc1
Reactant: C=CCCCCCCCCCCC=C
Product: C=CCCCCCCCCCCCCP(c1ccccc1)c1ccccc1
Yield: 36.8 %

Procedure:
A magnetically stirred solution of an equimolar mixture of 93 grams (0.5 moles) of diphenyl phosphine and 97 g (0.5 moles) of 1,13-tetradecadiene in a closed cylindrical quartz tube was irradiated from about 3 cm distance with two 75 Watt Hanau tube immersion lamps with a wide spectrum of ultraviolet radiation, in a 15° C. water bath for 28 hours. A subsequent nmr analysis indicated a partial disappearance of the double bond due to the diphenyl phosphine addition. The resulting reaction mixture was fractionally distilled to recover the unreacted tetradecadiene and diphenyl phosphine and to obtain 70 g (35%) of 13-tetradecenyl diphenyl phosphine monoadduct as a clear colorless liquid distillate of bp. 185°-190° C. at 0.05 mm. The terminal olefinic unsaturation was clearly indicated by the nmr pattern of the vinylic portions of the distillate product. Anal. Calcd. for C26H37P; C, 82.06; H, 9.80; P, 8.14 Found: C, 82.02, H, 9.60; P, 8.32.
Reaction SMILES: [C:1]([O:8]C)(=[O:7])[CH2:2][CH2:3][C:4]([O-:6])=[O:5].[CH3:10][O:11][C:12]1[CH:13]=[C:14]([CH2:19][C@@H:20]2[C@@H:25]([CH2:26][C:27]3[CH:28]=[CH:29][C:30]([OH:35])=[C:31]([O:33][CH3:34])[CH:32]=3)[C:23](=[O:24])[O:22][CH2:21]2)[CH:15]=[CH:16][C:17]=1[OH:18].N1C=CC=C[CH:37]=1>C(Cl)Cl>[CH3:10][O:11][C:12]1[CH:13]=[C:14]([CH2:19][C@@H:20]2[C@@H:25]([CH2:26][C:27]3[CH:28]=[CH:29][C:30]([OH:35])=[C:31]([O:33][CH3:34])[CH:32]=3)[C:23](=[O:24])[O:22][CH2:21]2)[CH:15]=[CH:16][C:17]=1[OH:18].[CH3:37][CH:3]([CH2:2][C:1]([O-:8])=[O:7])[C:4]([O-:6])=[O:5]
Reactant: COC(=O)CCC(=O)[O-]
Reactant: c1ccncc1
Agent: COc1cc(C[C@H]2COC(=O)[C@@H]2Cc2ccc(O)c(OC)c2)ccc1O
Solvent: ClCCl
Product: CC(CC(=O)[O-])C(=O)[O-]
Temperature: 60 °C

Procedure:
Monomethyl succinate (1 g, 7.56 mmol) was stirred in a flame dried round bottomed flask. Thionyl chloride was added (30 ml, 4.5 g) dropwise and the mixture was heated to 60° C. for 3 h. Then, excess thionyl chloride was remowed under reduced pressure and the residue was analysed by NMR spectroscopy. The fully chlorinated product was dissolved in 20 ml dry CH2Cl2 and dropwise added to a solution of matairesinol (1 g) in 40 ml CH2Cl2 and 1.8 g pyridine (8 eqv.) at 0° C. The mixture was stirred and allowed to warm to room temp over night. The mixture was then extracted with 2×50 ml water and the organic phase was dried and concentrated. The residue was chromatographed on a silica column (eluent EtOAc:PE 1:1) to yield a fraction containing the product. Yield 1.1 g (purity 80%, NMR, some other components present). The product was rechromatographed with CHCl3 to yield 0.92 g (70%) of a pure fraction containing two components, totally coeluting. The mixture was analysed with LC-MS (ESI-ion trap) and the components were identified as free matairesinol and matairesinol bis methylsuccinate (product). According to NMR analyses the product contained approximately 15% free matairesinol. It seems unlikely that the components can be separated by normal column chromatography. However, pure product can probably be obtained by varying the ratio of reagents (excess of acid chloride).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5](F)=[C:6]([C:8]([C:10]2[NH:11][CH:12]=[CH:13][CH:14]=2)=O)[CH:7]=1.O.[NH2:17][NH2:18]>O>[Br:1][C:2]1[CH:7]=[C:6]2[C:5](=[CH:4][CH:3]=1)[NH:18][N:17]=[C:8]2[C:10]1[NH:11][CH:12]=[CH:13][CH:14]=1
Reactant: O=C(c1ccc[nH]1)c1cc(Br)ccc1F
Reactant: NN
Solvent: O
Product: Brc1ccc2[nH]nc(-c3ccc[nH]3)c2c1
Temperature: 150 °C
Yield: 99 %

Procedure:
A slurry containing (5-bromo-2-fluoro-phenyl)-(1H-pyrrol-2-yl)-methanone (Preparation #16b, 2.40 g, 8.96 mmol) and hydrazine hydrate (35 mL) was sealed and heated by microwave iat about 150° C. for about 1 hour. The reaction was cooled to ambient temperature and diluted with water (150 mL). The product was extracted with EtOAc (150 mL), washed with 2N HCl solution (50 mL), saturated NaHCO3 solution (50 mL) and finally a saturated NaCl solution. The EtOAc layer was dried over anhydrous MgSO4, filtered and concentrated under reduced pressure to yield 5-bromo-3-(1H-pyrrol-2-yl)-1H-indazole (2.38 g, 99%) as an oil. RP HPLC (Table 1, Method e) Rt=2.95; m/z: (MH)+ 262/264
Reaction SMILES: [C:1]([C:9]1[CH:14]=[CH:13][C:12]([OH:15])=[CH:11][CH:10]=1)([CH2:4][C:5]([CH3:8])([CH3:7])[CH3:6])([CH3:3])[CH3:2].[C:16](O)([CH3:19])([CH3:18])[CH3:17]>C(O)(C(F)(F)F)=O.O>[C:16]([C:13]1[CH:14]=[C:9]([C:1]([CH2:4][C:5]([CH3:8])([CH3:7])[CH3:6])([CH3:2])[CH3:3])[CH:10]=[CH:11][C:12]=1[OH:15])([CH3:19])([CH3:18])[CH3:17]
Reactant: CC(C)(C)O
Reactant: CC(C)(C)CC(C)(C)c1ccc(O)cc1
Solvent: O
Solvent: O=C(O)C(F)(F)F
Product: CC(C)(C)CC(C)(C)c1ccc(O)c(C(C)(C)C)c1
Yield: 54 %

Procedure:
4-t-octylphenol (160 g, 0.78 mole) was dissolved in 400 ml anhydrous TFA. T-butyl alcohol (94.3 g, 1.27 mole) was added with stirring. The mixture was stoppered and stirred for 24 hours at ambient (~22° C.) temperature. This solution was diluted with 600 ml water, and the resulting upper organic layer was isolated in a separatory funnel. The crude product, 2-t-butyl-4-t-octylphenol, was dried over anhydrous magnesium sulfate and purified by eluting 35 g of the mixture with 70:30 hexanes:dichloromethane (v/v) in a 5×20 cm silica column, then eluted with 300 to 700 ml of solvent and collected in aliquots of 50 ml. Aliquots showing a single spot by TLC on silica eluted with 70:30 hexanes:dichloromethane (v/v) were combined and rotoevaporated to a thick syrup for a yield of 54%.
Reaction SMILES: [H-].[Na+].[NH:3]1[CH:7]=[CH:6][N:5]=[CH:4]1.[Cl:8][C:9]1[CH:10]=[C:11]([C:17]2[CH:21]=[CH:20][N:19]([CH2:22][C@@H:23]([NH:25][C:26]([C:28]3[N:29]=[C:30]([CH2:33]Cl)[O:31][CH:32]=3)=[O:27])[CH3:24])[N:18]=2)[CH:12]=[CH:13][C:14]=1[C:15]#[N:16]>CN(C=O)C>[N:3]1([CH2:33][C:30]2[O:31][CH:32]=[C:28]([C:26]([NH:25][CH:23]([CH3:24])[CH2:22][N:19]3[CH:20]=[CH:21][C:17]([C:11]4[CH:12]=[CH:13][C:14]([C:15]#[N:16])=[C:9]([Cl:8])[CH:10]=4)=[N:18]3)=[O:27])[N:29]=2)[CH:7]=[CH:6][N:5]=[CH:4]1
Reactant: c1c[nH]cn1
Reactant: C[C@@H](Cn1ccc(-c2ccc(C#N)c(Cl)c2)n1)NC(=O)c1coc(CCl)n1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CC(Cn1ccc(-c2ccc(C#N)c(Cl)c2)n1)NC(=O)c1coc(Cn2ccnc2)n1
Temperature: 0 °C
Reaction time: 1 h
Yield: 8.23 %

Procedure:
Sodium hydride (11.87 mg, 0.297 mmol) was added into a flask under nitrogen atmosphere. The flask was cooled to 0° C. and DMF was added through a septum. Imidazole (13.47 mg, 0.198 mmol) was added and the mixture was stirred for 60 min in RT. The mixture was again cooled to 0° C. and (S)—N-(1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)-2-(chloromethyl)oxazole-4-carboxamide (80 mg, 0.198 mmol) in DMF was added dropwise. The reaction mixture was stirred overnight in RT. DMF was evaporated and the resulting crude product was dissolved in DCM, washed with brine and evaporated. The product was triturated using diethyl ether and purified by Flash-chromatography. Yield 8.23%. 1H-NMR (400 MHz; CDCl3): δ 1.24 (d, 3H), 4.29 (dd, 1H), 4.41 (dd, 1H), 4.58 (m, 1H), 5.26 (s, 2H), 6.64 (d, 1H), 7.00 (t, 1H), 7.11 (t, 1H), 7.49 (d, 1H), 7.60 (s, 1H), 7.61 (d, 1H), 7.68 (d, 1H), 7.78 (dd, 1H), 8.08 (d, 1H), 8.17 (s, 1H).
Reaction SMILES: [NH2:1][C:2]1[C:3]([C:7]2[NH:23][C:10]3=[CH:11][C:12]4[C:13]([CH3:22])([CH3:21])[C:14](=[O:20])[N:15]([CH2:18][CH3:19])[C:16]=4[CH:17]=[C:9]3[N:8]=2)=[N:4][NH:5][CH:6]=1.[S:24]1[CH:28]=[CH:27][CH:26]=[C:25]1[C:29](Cl)=[O:30]>>[CH2:18]([N:15]1[C:16]2[CH:17]=[C:9]3[N:8]=[C:7]([C:3]4[C:2]([NH:1][C:29]([C:25]5[S:24][CH:28]=[CH:27][CH:26]=5)=[O:30])=[CH:6][NH:5][N:4]=4)[NH:23][C:10]3=[CH:11][C:12]=2[C:13]([CH3:22])([CH3:21])[C:14]1=[O:20])[CH3:19]
Reactant: O=C(Cl)c1cccs1
Reactant: CCN1C(=O)C(C)(C)c2cc3[nH]c(-c4n[nH]cc4N)nc3cc21
Product: CCN1C(=O)C(C)(C)c2cc3[nH]c(-c4n[nH]cc4NC(=O)c4cccs4)nc3cc21

Procedure:
Thiophene-2-carboxylic acid[3-(5-ethyl-7,7-dimethyl-6-oxo-1,5,6,7-tetrahydro-imidazo[4,5-f]indol-2-yl)-1H-pyrazol-4-yl]-amide was prepared using 2-(4-amino-1H-pyrazol-3-yl)-5-ethyl-7,7-dimethyl-5,7-dihydro-1H-imidazo[4,5-f]indol-6-one (250 mg, 0.81 mmol) and thiophene-2-carbonyl chloride (94 μl, 0.89 mmol). The title compound was obtained as yellow powder (54 mg, 15%).