Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[O:7][C:8]1[CH:9]=[C:10]([CH2:14][CH2:15][CH2:16][CH2:17][N:18]2C(=O)C3C(=CC=CC=3)C2=O)[CH:11]=[CH:12][CH:13]=1.O.NN>>[O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[O:7][C:8]1[CH:9]=[C:10]([CH2:14][CH2:15][CH2:16][CH2:17][NH2:18])[CH:11]=[CH:12][CH:13]=1
Reactant: O=C1c2ccccc2C(=O)N1CCCCc1cccc(OC2CCCCO2)c1
Agent: NN
Solvent: O
Product: NCCCCc1cccc(OC2CCCCO2)c1

Procedure:
Deprotection of 2-(4-(3-(tetrahydro-2H-pyran-2-yloxy)phenyl)butyl)isoindoline-1,3-dione with hydrazine monohydrate following the method used in Example 17 except that the reaction mixture was heated at +50° C. for 16 hrs afforded 4-(3-(tetrahydro-2H-pyran-2-yloxy)phenyl)butan-1-amine as a colorless oil, which was used in the next step without purification.
Reaction SMILES: [CH:1]1([N:4]2[CH2:9][C:8]3([CH2:14][CH2:13][N:12]([CH:15]([C:21]4[CH:26]=[CH:25][C:24]([C:27]5[CH:36]=[C:35]6[C:30]([CH:31]=[CH:32][CH:33]=[N:34]6)=[CH:29][CH:28]=5)=[CH:23][CH:22]=4)[CH2:16][C:17]([O:19]C)=[O:18])[CH2:11][CH2:10]3)[O:7][CH2:6][C:5]2=[O:37])[CH2:3][CH2:2]1.[Li+].[OH-]>C(O)C>[CH:1]1([N:4]2[CH2:9][C:8]3([CH2:10][CH2:11][N:12]([CH:15]([C:21]4[CH:22]=[CH:23][C:24]([C:27]5[CH:36]=[C:35]6[C:30]([CH:31]=[CH:32][CH:33]=[N:34]6)=[CH:29][CH:28]=5)=[CH:25][CH:26]=4)[CH2:16][C:17]([OH:19])=[O:18])[CH2:13][CH2:14]3)[O:7][CH2:6][C:5]2=[O:37])[CH2:3][CH2:2]1
Reactant: COC(=O)CC(c1ccc(-c2ccc3cccnc3c2)cc1)N1CCC2(CC1)CN(C1CC1)C(=O)CO2
Agent: [Li+]
Agent: [OH-]
Solvent: CCO
Product: O=C(O)CC(c1ccc(-c2ccc3cccnc3c2)cc1)N1CCC2(CC1)CN(C1CC1)C(=O)CO2
Temperature: 25 °C
Reaction time: 96 h
Yield: 72 %

Procedure:
A solution of methyl 3-(4-cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-3-(4-(quinolin-7-yl)phenyl)propanoate (0.238 mmol) in ethanol (1 mL) was treated with LiOH (0.476 mmol) and stirred at room temperature for four days. The reaction mixture was concentrated in vacuo and the residue purified by reverse phase HPLC (15-50% acetonitrile/water with 0.1% NH4OH) to afford the title compound as a white solid (72%). MS(ES)+ m/e 486.3 [M+H]+.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:26])[CH2:4][CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([CH2:12][NH:13][CH2:14][C:15]2[CH:20]=[CH:19][C:18]([C:21]3[S:22][CH:23]=[CH:24][N:25]=3)=[CH:17][CH:16]=2)[CH:7]=1.Cl.[N:28]1[CH:33]=[CH:32][CH:31]=[C:30]([S:34](Cl)(=[O:36])=[O:35])[CH:29]=1>C(N(CC)CC)C>[CH3:1][O:2][C:3](=[O:26])[CH2:4][CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([CH2:12][N:13]([S:34]([C:30]2[CH:29]=[N:28][CH:33]=[CH:32][CH:31]=2)(=[O:36])=[O:35])[CH2:14][C:15]2[CH:20]=[CH:19][C:18]([C:21]3[S:22][CH:23]=[CH:24][N:25]=3)=[CH:17][CH:16]=2)[CH:7]=1
Reactant: COC(=O)CCc1cccc(CNCc2ccc(-c3nccs3)cc2)c1
Reactant: O=S(=O)(Cl)c1cccnc1
Agent: Cl
Solvent: CCN(CC)CC
Product: COC(=O)CCc1cccc(CN(Cc2ccc(-c3nccs3)cc2)S(=O)(=O)c2cccnc2)c1

Procedure:
The title compound of Step A was prepared from 3-{3-[(4-thiazol-2-yl-benzylamino)-methyl]-phenyl}-propionic acid methyl ester, of 11e, and pyridine-3-sulfonyl chloride hydrochloride, of Preparation 2, following the method described in Example 1, Step B using triethylamine in place of N,N-diisopropylethylamine. 1H NMR (400 MHz, CDCl3) δ 8.68 (d, 1H), 7.97 (d, 1H), 7.87 (m, 2H), 7.79 (d, 2H), 7.47 (m, 1H), 7.33 (d, 1H), 7.18 (d, 2H), 7.12 (m, 1H), 7.02 (d, 1H), 6.94 (d, 1H), 6.90 (s, 1H), 4.52 (s, 2H), 4.47 (s, 2H), 3.65 (s, 3H), 2.80 (t, 2H), 2.50 (t, 2H); MS 508 (M+1).
Reaction SMILES: [NH2:1][C@H:2]([C:10]([OH:12])=[O:11])[CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.C(NC(=NC(C)C)O[CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)(C)C>O1CCCC1>[NH2:1][CH:2]([CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)[C:10]([O:12][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)=[O:11]
Reactant: CC(C)N=C(NC(C)C)OCc1ccccc1
Reactant: N[C@@H](Cc1ccccc1)C(=O)O
Solvent: C1CCOC1
Product: NC(Cc1ccccc1)C(=O)OCc1ccccc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
In a dry round bottomed flask, equipped with a magnetic stirrer, 13.22 g (80 mmol) of Phenylalanine is added to 18.75 g (80 mmol) of the oil, N,N′-diisopropyl-O-benzylisourea and stirred at room temperature for about one hour. After about one hour the volume of the reaction is increased by the addition of 350 mL of dry tetrahyrdofuran (THF), and stirred at room temperature for an additional 48 hours. The resultant mixture is then filtered in order to remove the by-product, diisopropylurea, and the THF is then evaporated from the filtrate at reduced pressure. The oil which remains is pumped under high vacuum for about 24 hours yielding the protected amino acid, benzyl 2-amino-3-phenylpropanoate, in pure enough form for subsequent steps.
Reaction SMILES: [F:1][C:2]([F:35])([F:34])[C:3]1[CH:4]=[C:5]([CH:27]=[C:28]([C:30]([F:33])([F:32])[F:31])[CH:29]=1)[CH2:6][N:7]1[C:13](=[O:14])[C:12]2[C:15]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[CH3:26])=[CH:16][C:17](Cl)=[N:18][C:11]=2[O:10][CH2:9][CH2:8]1.[N:36]1([CH:42]2[CH2:47][CH2:46][NH:45][CH2:44][CH2:43]2)[CH2:41][CH2:40][O:39][CH2:38][CH2:37]1>>[F:1][C:2]([F:35])([F:34])[C:3]1[CH:4]=[C:5]([CH:27]=[C:28]([C:30]([F:33])([F:32])[F:31])[CH:29]=1)[CH2:6][N:7]1[C:13](=[O:14])[C:12]2[C:15]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[CH3:26])=[CH:16][C:17]([N:45]3[CH2:46][CH2:47][CH:42]([N:36]4[CH2:41][CH2:40][O:39][CH2:38][CH2:37]4)[CH2:43][CH2:44]3)=[N:18][C:11]=2[O:10][CH2:9][CH2:8]1
Reactant: C1CC(N2CCOCC2)CCN1
Reactant: Cc1ccccc1-c1cc(Cl)nc2c1C(=O)N(Cc1cc(C(F)(F)F)cc(C(F)(F)F)c1)CCO2
Product: Cc1ccccc1-c1cc(N2CCC(N3CCOCC3)CC2)nc2c1C(=O)N(Cc1cc(C(F)(F)F)cc(C(F)(F)F)c1)CCO2
Yield: 12.8 %

Procedure:
In a similar manner to Example 1, 4-[3,5-bis(trifluoromethyl)benzyl]-8-chloro-6-(2-methylphenyl)-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine (51.5 mg) was reacted with 4-(morpholine-4-yl)piperidine (51.1 mg) to obtain 4-[3,5-bis(trifluoromethyl)benzyl]-6-(2-methylphenyl)-8-[4-(morpholine-4-yl)piperidine-1-yl]-5-oxo-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine (8.3 mg, 13%).
Reaction SMILES: [CH3:1][C:2]1[N:7]=[C:6]([NH2:8])[CH:5]=[C:4]([N:9]2[CH2:14][CH2:13][N:12]([CH3:15])[CH2:11][CH2:10]2)[N:3]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C(=O)([O-])[O-].[Cs+].[Cs+].Cl[C:65]1[N:70]=[C:69]([NH:71][C:72]2[C:80]3[O:79][CH2:78][O:77][C:76]=3[CH:75]=[CH:74][C:73]=2[Cl:81])[CH:68]=[CH:67][N:66]=1>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:81][C:73]1[CH:74]=[CH:75][C:76]2[O:77][CH2:78][O:79][C:80]=2[C:72]=1[NH:71][C:69]1[CH:68]=[CH:67][N:66]=[C:65]([NH:8][C:6]2[CH:5]=[C:4]([N:9]3[CH2:14][CH2:13][N:12]([CH3:15])[CH2:11][CH2:10]3)[N:3]=[C:2]([CH3:1])[N:7]=2)[N:70]=1
Reactant: Cc1nc(N)cc(N2CCN(C)CC2)n1
Reactant: Clc1nccc(Nc2c(Cl)ccc3c2OCO3)n1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21
Solvent: C1COCCO1
Product: Cc1nc(Nc2nccc(Nc3c(Cl)ccc4c3OCO4)n2)cc(N2CCN(C)CC2)n1
Temperature: 150 °C
Yield: 16 %

Procedure:
2-Methyl-6-(4-methylpiperazin-1-yl)pyrimidin-4-amine (71 mg), palladium acetate (1 mg), Xantphos (24 mg), caesium carbonate (166 mg) and 2-chloro-N-(5-chloro-1,3-benzodioxol-4-yl)pyrimidin-4-amine (117 mg) were dissolved in dioxane (4 ml) under nitrogen and heated in a microwave reactor at 150° C. for 60 minutes. The reaction was cooled and partitioned between ethyl acetate and water. The organic layer was dried and concentrated to give a brown solid that was purified by reverse phase chromatography to give N′-(5-chloro-1,3-benzodioxol-4-yl)-N-[2-methyl-6-(4-methylpiperazin-1-yl)pyrimidin-4-yl]pyrimidine-2,4-diamine as a yellow solid (25 mg, 13%); NMR Spectrum (300 MHz, CDCl3) 2.30 (s, 3H), 2.37 (s, 3H), 2.55 (br s, 4H), 3.64 (br s, 4H), 5.90 (s, 2H), 5.95 (d, 1H), 6.58-6.68 (m, 1H), 6.78-6.95 (m, 1H), 7.40 (s, 1H), 8.09 (d, 1H); Mass Spectrum M+ 455.
Reaction SMILES: [CH2:1]1[C:14]2[CH:5]([CH:6]3[C:11](=[CH:12][CH:13]=2)C=CCC3)[CH2:4][CH2:3][CH2:2]1.[Cl-].[Al+3].[Cl-].[Cl-]>C(Cl)Cl>[CH2:13]1[C:14]2[C:5](=[CH:4][CH:3]=[CH:2][CH:1]=2)[CH2:6][CH2:11][CH2:12]1
Reactant: C1=CC2=CC=C3CCCCC3C2CC1
Agent: [Al+3]
Agent: [Cl-]
Solvent: ClCCl
Product: c1ccc2c(c1)CCCC2
Temperature: -10 °C
Reaction time: 4 h

Procedure:
1000 g of the sym.-octahydrophenanthrene fraction of Example 1(b) and 250 ml methylene chloride were placed in a stirred flask and cooled to -10° C. Then 40 g of aluminum chloride powder were added in small quantities, while the temperature at times rose to -8° C. The mixture turning darkbrown was uniformly stirred. By crystallization of sym.-octahydroanthracene the addition of further 150 ml methylene chloride was required after about 4 hours. After an additional 2 hours 500 ml of 10 percent sodium hydroxide solution were added for decomposing the aluminum chloride, then the organic phase was separated and after removal of the solvent the organic phase was distilled in vacuum of 12 torr. There resulted in the sequence of the boiling points 5.5 g tetrahydronaphthalene (boiling point 82° C. at 12 torr), 958 g isomer mixture of a boiling point of 167°-168° C. at 12 torr comprising 97 percent sym.-octahydroanthracene and 3 percent sym.-octahydrophenanthrene, as well as a distillation residue of 34.8 g.
Reaction SMILES: [CH2:1]([N:3]([C:7]1[CH:8]=[C:9]([CH:14]=[CH:15][CH:16]=1)[CH2:10][CH2:11][C:12]#[N:13])[CH2:4][CH2:5][OH:6])[CH3:2].[C:17](OC(=O)C)(=[O:19])[CH3:18].C(=O)([O-])[O-].[Na+].[Na+]>C(O)(=O)C>[CH2:1]([N:3]([C:7]1[CH:8]=[C:9]([CH:14]=[CH:15][CH:16]=1)[CH2:10][CH2:11][C:12]#[N:13])[CH2:4][CH2:5][O:6][C:17](=[O:19])[CH3:18])[CH3:2]
Reactant: CC(=O)OC(C)=O
Reactant: CCN(CCO)c1cccc(CCC#N)c1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CC(=O)O
Product: CCN(CCOC(C)=O)c1cccc(CCC#N)c1

Procedure:
A mixture of 218 parts of 3-(N-ethyl-N-β-hydroxyethylamino)-hydrocinnamonitrile, 100 parts by volume of glacial acetic acid and 115 parts by volume of acetic anhydride was heated under reflux for 4 hours. At the end of the reaction, easily followed by chromatography on a thin layer of silica, the product was neutralized with sodium carbonate and 200 parts were decanted of 3-(N-ethyl-N-β-acetoxyethyl-amino)-hydrocinnamonitrile of the formula: ##STR17## in the form of an oil which boiled at 192° C. under 20 mm of mercury.
Reaction SMILES: [Si:1]([O:18][CH2:19][CH:20]([CH2:24][CH2:25][CH2:26][Br:27])[CH2:21][CH2:22][Br:23])([C:14]([CH3:17])([CH3:16])[CH3:15])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Si](OC[C@@H](CCCO)CCO)(C(C)(C)C)(C1C=CC=CC=1)C1C=CC=CC=1.BrN1C(=O)CCC1=O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>>[Si:1]([O:18][CH2:19][C@@H:20]([CH2:24][CH2:25][CH2:26][Br:27])[CH2:21][CH2:22][Br:23])([C:14]([CH3:17])([CH3:16])[CH3:15])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CC(C)(C)[Si](OCC(CCBr)CCCBr)(c1ccccc1)c1ccccc1
Agent: CC(C)(C)[Si](OC[C@H](CCO)CCCO)(c1ccccc1)c1ccccc1
Agent: O=C1CCC(=O)N1Br
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Product: CC(C)(C)[Si](OC[C@H](CCBr)CCCBr)(c1ccccc1)c1ccccc1
Yield: 75 %

Procedure:
Following the same procedure described for the preparation of racemic dibromide, 3-(tert-butyldiphenylsilyloxymethyl)-1,6-dibromohexane, (S)-(-)-3-(tert-butyldiphenylsilyloxymethyl)-1,6-hexanediol (4.85 g, 12.53 mmol) was reacted with N-bromosuccinimide (5.35 g, 30.1 mmol) and triphenylphosphine (7.87 g, 30.1 mmol) CH2Cl2 (150 mL) at 0° C. to afford compound (S)-(-)-3-(tert-butyldiphenylsilyloxymethyl)-1,6-dibromohexane 4.81 (75%) as a clear, colorless oil which was homogenous by TLC (Rf =0.8, 10% EtOAc in hexanes. Both the TLC properties and 1H spectra of this compound were identical in all respects with racemic isomer. MS.
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([F:12])=[CH:9][CH:10]=2)[N:5]=[C:4]([C:13]2[CH:18]=[C:17]([CH3:19])[CH:16]=[CH:15][N:14]=2)[C:3]=1[CH3:20].[NH:21]1[CH2:26][CH2:25][S:24][C:23]2[N:27]=[CH:28][C:29]([N:31]3[CH2:36][CH2:35][O:34][CH2:33][CH2:32]3)=[CH:30][C:22]1=2.CC(C)([O-])C.[Na+]>CC(C1C=C(C(C)C)C(C2C(P(C3CCCCC3)C3CCCCC3)=CC=CC=2)=C(C(C)C)C=1)C.C1C=[C-]C(CCN)=CC=1.Cl[Pd+].C1(C)C=CC=CC=1>[F:12][C:8]1[CH:7]=[C:6]2[C:11]([C:2]([N:21]3[CH2:26][CH2:25][S:24][C:23]4[N:27]=[CH:28][C:29]([N:31]5[CH2:32][CH2:33][O:34][CH2:35][CH2:36]5)=[CH:30][C:22]3=4)=[C:3]([CH3:20])[C:4]([C:13]3[CH:18]=[C:17]([CH3:19])[CH:16]=[CH:15][N:14]=3)=[N:5]2)=[CH:10][CH:9]=1
Reactant: Cc1ccnc(-c2nc3cc(F)ccc3c(Cl)c2C)c1
Reactant: c1nc2c(cc1N1CCOCC1)NCCS2
Agent: Cl[Pd+]
Agent: CC(C)(C)[O-]
Agent: CC(C)c1cc(C(C)C)c(-c2ccccc2P(C2CCCCC2)C2CCCCC2)c(C(C)C)c1
Solvent: Cc1ccccc1
Product: Cc1ccnc(-c2nc3cc(F)ccc3c(N3CCSc4ncc(N5CCOCC5)cc43)c2C)c1

Procedure:
Prepared according to procedure Y by using 4-chloro-7-fluoro-3-methyl-2-(4-methylpyridin-2-yl)quinoline (54 mg, 0.19 mmol), 4-(2,3-dihydro-1H-pyrido[2,3-b][1,4]thiazin-7-yl)morpholine (45 mg, 0.19 mmol), sodium tert-butoxide (36 mg, 0.38 mmol), XPhos precatalyst (14 mg, 0.019 mmol) in toluene (4 mL) for 1 h at 110° C. Purification by column chromatography (gradient of DCM to (DCM:MeOH:NH4OH, 90:9:1) from 1:0 to 8:2) gave 4-(1-(7-fluoro-3-methyl-2-(4-methylpyridin-2-yl)quinolin-4-yl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]thiazin-7-yl)morpholine. Mass Spectrum (ESI) m/e=488.0 (M+1).
Reaction SMILES: [OH:1][CH:2]1[CH2:6][CH2:5][CH:4]([CH:7]=[CH:8][CH:9]([OH:15])[CH2:10][CH2:11][CH2:12][CH2:13][CH3:14])[CH:3]1[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][C:22]([O:24]C)=O.[CH3:26][NH2:27].[O-]CC.[Na+].[Na]>C(O)C>[CH3:26][NH:27][C:22](=[O:24])[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17][CH2:16][CH:3]1[CH:4]([CH:7]=[CH:8][CH:9]([OH:15])[CH2:10][CH2:11][CH2:12][CH2:13][CH3:14])[CH2:5][CH2:6][CH:2]1[OH:1]
Reactant: CCCCCC(O)C=CC1CCC(O)C1CCCCCCC(=O)OC
Reactant: CN
Agent: CC[O-]
Agent: [Na+]
Agent: [Na]
Solvent: CCO
Product: CCCCCC(O)C=CC1CCC(O)C1CCCCCCC(=O)NC
Yield: 25 %

Procedure:
To a solution of methyl 7-[2-hydroxy-5-(3-hydroxy-1-octenyl)cyclopentyl]heptanoate (0.8 g.) [prepared as described in Example 5] in ethanol (16 ml.) was added 33% methylamine in ethanol (4 ml.) followed by sodium ethoxide in ethanol [0.8 ml. of a solution prepared by dissolving sodium (0.2 g.) in ethanol (1 ml.)]. The resulting solution was refluxed for 1 day and the ethanol removed in vacuo. The residue was diluted with ice-cooled water and extracted twice with dichloromethane. The combined dichloromethane extracts were dried over magnesium sulphate and evaporated to give N-methyl-7-[2-hydroxy-5-(3-hydroxy-1-octenyl)cyclopentyl]heptanoamide (0.2g., 25%). Found: C, 71.9; H, 10.6. C21H39NO3 requires C, 71.4; H, 11.05%) νmax 3300 cm-1, 1650 cm-1, 1570 cm-1 and 980 cm-1 (liquid film).
Reaction SMILES: [CH3:1][C:2]1[CH2:11][CH2:10][C:6](=[C:7]([CH3:9])[CH3:8])[C:4](=[O:5])[CH:3]=1.CC(C1C(OC)=C(C(C)(C)C)C=C(P(C2C=C(C(C)(C)C)C(OC)=C(C(C)(C)C)C=2)C2C=CC3OCOC=3C=2C2C3OCOC=3C=CC=2P(C2C=C(C(C)(C)C)C(OC)=C(C(C)(C)C)C=2)C2C=C(C(C)(C)C)C(OC)=C(C(C)(C)C)C=2)C=1)(C)C.[H][H]>C(OCC)(=O)C>[CH3:1][CH:2]1[CH2:3][CH:4]([OH:5])[C:6](=[C:7]([CH3:8])[CH3:9])[CH2:10][CH2:11]1
Reactant: [H][H]
Reactant: CC1=CC(=O)C(=C(C)C)CC1
Agent: COc1c(C(C)(C)C)cc(P(c2cc(C(C)(C)C)c(OC)c(C(C)(C)C)c2)c2ccc3c(c2-c2c(P(c4cc(C(C)(C)C)c(OC)c(C(C)(C)C)c4)c4cc(C(C)(C)C)c(OC)c(C(C)(C)C)c4)ccc4c2OCO4)OCO3)cc1C(C)(C)C
Solvent: CCOC(C)=O
Product: CC(C)=C1CCC(C)CC1O
Reaction time: 20 h
Yield: 88.7 %

Procedure:
A 500 ml capacity autoclave was charged with 150 g (1 mol) of piperitenone, 18.6 mg (0.04 mmol) of [Rh(cod)2]PF6, 47.2 mg (0.04 mmol) of (S)-DTBM-SEGPHOS, 14.8 mg (0.02 mmol) of BrPPh3(CH2)4PPh3Br and 7.5 ml of ethyl acetate, and the reaction was carried out at 50° C. for 20 hours under a hydrogen pressure of 3 Mpa. After completion of the reaction, hydrogen was purged, the reaction solution was concentrated and then distillation was carried out under a reduced pressure to obtain 136.8 g of pulegol. The yield was 90%.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([C:11]1[CH:16]=[CH:15][C:14]([C:17]#[N:18])=[CH:13][CH:12]=1)[N:6]=[CH:5]2.[O:19]1[CH2:24][CH2:23][N:22]([C:25]2[CH:33]=[CH:32][C:28]([C:29]([O-])=[O:30])=[CH:27][CH:26]=2)[CH2:21][CH2:20]1>>[C:17]([C:14]1[CH:15]=[CH:16][C:11]([N:7]2[C:8]3[C:4](=[CH:3][C:2]([NH:1][C:29](=[O:30])[C:28]4[CH:27]=[CH:26][C:25]([N:22]5[CH2:23][CH2:24][O:19][CH2:20][CH2:21]5)=[CH:33][CH:32]=4)=[CH:10][CH:9]=3)[CH:5]=[N:6]2)=[CH:12][CH:13]=1)#[N:18]
Reactant: O=C([O-])c1ccc(N2CCOCC2)cc1
Reactant: N#Cc1ccc(-n2ncc3cc(N)ccc32)cc1
Product: N#Cc1ccc(-n2ncc3cc(NC(=O)c4ccc(N5CCOCC5)cc4)ccc32)cc1

Procedure:
Compound 405 was prepared according to the procedure described in Scheme IV from 5-amino-1-(4-cyanophenyl)indazole and 4-morpholinobenzoate. [M+H]+ calcd for C25H21N5O2: 424.17; found: 424.09.
Reaction SMILES: C(CC[C:6]1[CH:11]=[CH:10][C:9]([C:12]2[C:13]([CH3:43])([CH3:42])[C@H:14]3[C@:27]([CH3:30])([CH2:28][CH:29]=2)[C@@H:26]2[C@:17]([CH3:41])([C@@:18]4([CH3:40])[C@H:23]([CH2:24][CH2:25]2)[C@H:22]2[C@H:31]([C:34]([CH3:36])=[CH2:35])[CH2:32][CH2:33][C@:21]2([C:37]([OH:39])=[O:38])[CH2:20][CH2:19]4)[CH2:16][CH2:15]3)=[CH:8][CH:7]=1)(O)=O.B(C1C=CC([C:53]2([C:56]([OH:58])=[O:57])[CH2:55][CH2:54]2)=CC=1)(O)O.B(O)O>>[C:56]([C:53]1([C:6]2[CH:7]=[CH:8][C:9]([C:12]3[C:13]([CH3:43])([CH3:42])[C@H:14]4[C@:27]([CH3:30])([CH2:28][CH:29]=3)[C@@H:26]3[C@:17]([CH3:41])([C@@:18]5([CH3:40])[C@H:23]([CH2:24][CH2:25]3)[C@H:22]3[C@H:31]([C:34]([CH3:36])=[CH2:35])[CH2:32][CH2:33][C@:21]3([C:37]([OH:39])=[O:38])[CH2:20][CH2:19]5)[CH2:16][CH2:15]4)=[CH:10][CH:11]=2)[CH2:55][CH2:54]1)([OH:58])=[O:57]
Reactant: O=C(O)C1(c2ccc(B(O)O)cc2)CC1
Reactant: C=C(C)[C@@H]1CC[C@]2(C(=O)O)CC[C@]3(C)[C@H](CC[C@@H]4[C@@]5(C)CC=C(c6ccc(CCC(=O)O)cc6)C(C)(C)[C@@H]5CC[C@]43C)[C@@H]12
Agent: OBO
Product: C=C(C)[C@@H]1CC[C@]2(C(=O)O)CC[C@]3(C)[C@H](CC[C@@H]4[C@@]5(C)CC=C(c6ccc(C7(C(=O)O)CC7)cc6)C(C)(C)[C@@H]5CC[C@]43C)[C@@H]12

Procedure:
The title compound was prepared following the methods described above for compound (1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-9-(4-(2-carboxyethyl)phenyl)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysene-3a-carboxylic acid (example 4a) using 1-(4-boronophenyl)cyclopropanecarboxylic acid as the reactant boronic acid. The product was isolated as a white solid (1.76 mg, 5%). LCMS: m/e 597.64 (M−H)−, 4.43 min (method 2). 1H NMR (599 MHz, DMSO-D6_CDCl3) δ ppm 0.92 (s, 3H), 0.94 (s, 3H), 0.99 (d, J=3.52 Hz, 6H), 1.02 (s, 3H), 1.03-1.71 (m, 21H), 1.71 (s, 3H), 1.82-1.95 (m, 2H), 2.10 (dd, J=17.28, 6.15 Hz, 1H), 2.20 (d, J=12.30 Hz, 1H), 2.30-2.39 (m, 1H), 2.97-3.09 (m, 1H), 4.61 (br. s, 1H), 4.74 (s, 1H), 5.25 (d, J=4.69 Hz, 1H), 7.04 (d, J=7.62 Hz, 2H), 7.25 (d, J=7.62 Hz, 2H).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6]([CH2:11][OH:12])=[CH:5]2.N[C:14]1[CH:15]=[C:16]2[C:20](=[CH:21][CH:22]=1)N[C:18]([C:23]([O:25]CC)=O)=[CH:17]2.[H-].[Al+3].[Li+].[H-].[H-].[H-]>>[C:4]([C:22]1[CH:14]=[CH:15][C:16](/[CH:17]=[CH:18]/[C:23]([NH:1][C:2]2[CH:3]=[C:4]3[C:8](=[CH:9][CH:10]=2)[NH:7][C:6]([CH2:11][OH:12])=[CH:5]3)=[O:25])=[CH:20][CH:21]=1)([CH3:8])([CH3:5])[CH3:3]
Reactant: Nc1ccc2[nH]c(CO)cc2c1
Reactant: CCOC(=O)c1cc2cc(N)ccc2[nH]1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Product: CC(C)(C)c1ccc(/C=C/C(=O)Nc2ccc3[nH]c(CO)cc3c2)cc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
(5-Aminoindol-2-yl)methan-1-ol. Ethyl 5-aminoindole-2-carboxylate, Example 74(a), (1.5 g, 7.3 mmol) was transferred to a round-bottomed flask and treated with lithium aluminum hydride (10 mL, 10 mmol, 1.0 M in THF, Aldrich) under N2. The reaction mixture was magnetically stirred at 25° C. for 1 h, then quenched by the dropwise addition of H2O (0.5 mL) followed by 20% aq. KOH (30 mL). The suspension was filtered and the aqueous phase extracted with EtOAc. The organic extract was concentrated in vacuo. Purification of the crude product by silica gel chromatography (20:80 hexane:EtOAc) provided the title product. MS (ESI, pos. ion) m/z: 163 (M+1).
Reaction SMILES: C(OC(=O)[NH:7][C:8]1[O:9][CH2:10][CH2:11][C@:12]([C:15]2[CH:20]=[C:19]([NH2:21])[CH:18]=[CH:17][C:16]=2[F:22])([CH3:14])[N:13]=1)(C)(C)C.[CH3:24][O:25][C:26]1[C:27]([C:32](O)=[O:33])=[N:28][CH:29]=[CH:30][CH:31]=1>>[NH2:7][C:8]1[O:9][CH2:10][CH2:11][C@:12]([C:15]2[CH:20]=[C:19]([NH:21][C:32]([C:27]3[C:26]([O:25][CH3:24])=[CH:31][CH:30]=[CH:29][N:28]=3)=[O:33])[CH:18]=[CH:17][C:16]=2[F:22])([CH3:14])[N:13]=1
Reactant: CC(C)(C)OC(=O)NC1=N[C@](C)(c2cc(N)ccc2F)CCO1
Reactant: COc1cccnc1C(=O)O
Product: COc1cccnc1C(=O)Nc1ccc(F)c([C@]2(C)CCOC(N)=N2)c1

Procedure:
The coupling of [(S)-4-(5-amino-2-fluoro-phenyl)-4-methyl-5,6-dihydro-4H-[1,3]oxazin-2-yl]-carbamic acid tert-butyl ester from experiment F (R1=Me) and 3-methoxy-pyridine-2-carboxylic acid followed by deprotection using procedure H yielded the title compound.
Reaction SMILES: Cl[C:2]1[CH:3]=[CH:4][C:5]2[O:14][CH2:13][CH2:12][C:11]3[CH:10]=[C:9]([C:15]4[N:16]([C:20]5[CH:25]=[CH:24][C:23]([F:26])=[CH:22][C:21]=5[F:27])[N:17]=[CH:18][N:19]=4)[S:8][C:7]=3[C:6]=2[N:28]=1.C[Si](C)(C)[O:31][CH:32]1[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]1.C(N1CCN2CCN(CCCC)P1N(CCCC)CC2)CCC.CC(C)([O-])C>O1CCOCC1.CC([O-])=O.CC([O-])=O.[Pd+2]>[F:27][C:21]1[CH:22]=[C:23]([F:26])[CH:24]=[CH:25][C:20]=1[N:16]1[C:15]([C:9]2[S:8][C:7]3[C:6]4[N:28]=[C:2]([N:35]5[CH2:36][CH2:37][CH:32]([OH:31])[CH2:33][CH2:34]5)[CH:3]=[CH:4][C:5]=4[O:14][CH2:13][CH2:12][C:11]=3[CH:10]=2)=[N:19][CH:18]=[N:17]1
Reactant: Fc1ccc(-n2ncnc2-c2cc3c(s2)-c2nc(Cl)ccc2OCC3)c(F)c1
Reactant: C[Si](C)(C)OC1CCNCC1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: CC(C)(C)[O-]
Solvent: C1COCCO1
Product: OC1CCN(c2ccc3c(n2)-c2sc(-c4ncnn4-c4ccc(F)cc4F)cc2CCO3)CC1
Temperature: 120 °C
Reaction time: 0.1 h
Yield: 37.5 %

Procedure:
A mixture of 9-Chloro-2-[2-(2,4-difluoro-phenyl)-2H-[1,2,4]triazol-3-yl]-4,5-dihydro-6-oxa-1-thia-10-aza-benzo[e]azulene (300 mg, 0.72 mmol), Pd(OAc)2 (49 mg, 0.3 mmol), 4-Tri-methylsilanyloxy-piperidine (186 mg, 1.44 mmol), 2,8,9-tributyl-2,5,8,9-tetraaza-1-phosphabicyclo[3.3.3]undecane (99 mg, 0.29 mmol), tert-butoxide (140 mg, 1.44 mmol) in dioxane (2 mL) was bubbled N2 for 10 min and then stirred at 120° C. for 6 min under the irradition of microwave. The mixture was filtered over ceilite. The filtrate was concentrated to dryness and purified by pre-HPLC to afford 130 mg of 124 (yield=38%). 1H NMR (MeOD, 400 MHz): δ8.11 (s, 1H), 7.68-7.66 (m, 1H), 7.33-7.23 (m, 3H), 7.10-7.08 (m, 1H), 6.54-6.52 (m, 1H), 4.16-4.13 (m, 2H), 3.90-3.86 (m, 2H), 3.76-3.72 (m, 2H), 3.07-3.04 (m, 2H), 2.95-2.89 (m, 2H), 1.86-1.82 (m, 2H), 1.44-1.41 (m, 2H). LC-MS (ESI): m/z=482 [M+H]+
Reaction SMILES: [CH2:1]([C:3]1[CH:8]=[CH:7][C:6]([F:9])=[CH:5][CH:4]=1)[CH3:2].C1C(=O)N([Br:17])C(=O)C1.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1>C(Cl)(Cl)(Cl)Cl>[Br:17][CH:1]([C:3]1[CH:8]=[CH:7][C:6]([F:9])=[CH:5][CH:4]=1)[CH3:2]
Reactant: O=C1CCC(=O)N1Br
Reactant: CCc1ccc(F)cc1
Agent: O=C(OOC(=O)c1ccccc1)c1ccccc1
Solvent: ClC(Cl)(Cl)Cl
Product: CC(Br)c1ccc(F)cc1
Temperature: 80 °C
Reaction time: 5 h
Yield: 81.3 %

Procedure:
A mixture of 1-ethyl-4-fluorobenzene (0.248 g, 2 mmol), NBS (0.35 g, 2 mmol) and benzoyl peroxide (0.14 g, 0.6 mmol) were dissolved in 20 mL CCl4, The mixture was stirred at 80° C. for 5 hours and then the reaction was conc. in vacuo and resulting oil was purified via silica gel chromatography (PE-EtOAC 5:1) to give the title compound (330 mg, 80%) as a yellow oil. LCMS 202 (M+H+).