Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH2:15][CH2:14][N:13]([C:16]3[CH:21]=[CH:20][N:19]=[CH:18][CH:17]=3)[CH2:12][CH2:11]2)=[CH:6][CH:5]=1)([O-])=O>C(O)C.[Pd]>[NH2:1][C:4]1[CH:5]=[CH:6][C:7]([N:10]2[CH2:15][CH2:14][N:13]([C:16]3[CH:21]=[CH:20][N:19]=[CH:18][CH:17]=3)[CH2:12][CH2:11]2)=[CH:8][CH:9]=1
Reactant: O=[N+]([O-])c1ccc(N2CCN(c3ccncc3)CC2)cc1
Agent: [Pd]
Solvent: CCO
Product: Nc1ccc(N2CCN(c3ccncc3)CC2)cc1
Yield: 58.3 %

Procedure:
A mixture of 1-(4-nitrophenyl)-4-(4-pyridyl)piperazine (2.07 g) in ethanol (100 ml) was hydrogenated at room temperature under a pressure of 2 bars in the presence of 10% palladium on charcoal (0.25 g). When reduction was complete, the catalyst was filtered off and the filtrate was evaporated. The residue was crystallised from methanol/ethyl acetate to give 1-(4-aminophenyl)-4-(4-pyridyl)piperazine (1.08 g), m.p. 210°-211° C. Found: C,70.47; H,7.07; N,21.56. C15H18N4 requires: C,70.83; H,7.13; N,22.03%.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([NH:9]C(=O)C)=[C:4]([O:13][CH3:14])[C:3]=1[N+:15]([O-:17])=[O:16].[Na]>Cl>[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([NH2:9])=[C:4]([O:13][CH3:14])[C:3]=1[N+:15]([O-:17])=[O:16]
Reactant: COc1c(NC(C)=O)c(F)cc(Cl)c1[N+](=O)[O-]
Agent: Cl
Agent: [Na]
Product: COc1c(N)c(F)cc(Cl)c1[N+](=O)[O-]
Temperature: 20 °C
Reaction time: 8 h

Procedure:
A suspension of 40.0 g (152 mmol) of N-(4-chloro-6-fluoro-2-methoxy-3-nitrophenyl)acetamide in 800 ml of 6M hydrochloric acid was heated for 5 hours at reflux temperature, whereupon the mixture was stirred overnight at approximately 20° C. For work-up, the reaction mixture was stirred into ice-water. The pH was brought to 8-9 by adding sodium solution. The mixture was subsequently extracted six times with ethyl acetate. The combined organic phases were dried over magnesium sulfate and then concentrated under reduced pressure. Yield: 33 g (98%);
Reaction SMILES: [CH3:1][C:2](C)([O-:4])[CH3:3].[K+].[Br:7][C:8]1[CH:9]=[C:10]2[C:15](=[CH:16][CH:17]=1)[N:14]=[CH:13][N:12]=[C:11]2Cl.CC(O)C>C1COCC1>[Br:7][C:8]1[CH:9]=[C:10]2[C:15](=[CH:16][CH:17]=1)[N:14]=[CH:13][N:12]=[C:11]2[O:4][CH:2]([CH3:3])[CH3:1]
Reactant: CC(C)(C)[O-]
Reactant: Clc1ncnc2ccc(Br)cc12
Agent: [K+]
Solvent: C1CCOC1
Solvent: CC(C)O
Product: CC(C)Oc1ncnc2ccc(Br)cc12
Temperature: 50 °C
Reaction time: 0.5 h
Yield: 87 %

Procedure:
Potassium t-butoxide (4.1 ml, 4.1 mmol; 1M in THF) was added to a suspension mixture of 6-bromo-4-chloro-quinazoline (1.0 g, 4.0 mmol) and 2-propanol (0.313 ml, 4.1 mmol) in THF (20 ml). After stirring at 50° C. for 30 minutes, the mixture was cooled to room temperature and the THF was removed in vacuo. The residue was taken up in ethyl acetate (50 ml) and the organic layer was washed with water followed by brine. The organic layer was dried over Na2SO4 and the residue purified by silica gel chromatography with gradient of 11 to 32% ethylacetate-hexane. Product containing fractions were pooled and concentrated to afford the title compound as beige solid (0.93 g, yield: 85%). The resulting compound was characterized as follows: MS (m/z) 266.75 [M+H]+; HPLC Rt=1.68 minutes (Method A).
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([O:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH:3]=1.[CH2:15]([Sn](CCCC)(CCCC)CCCC)[CH:16]=[CH2:17].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Li+].[Cl-]>CN(C=O)C.CCOCC.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH2:17]([C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([O:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH:3]=1)[CH:16]=[CH2:15]
Reactant: Brc1cccc(Oc2ccccc2)c1
Reactant: C=CC[Sn](CCCC)(CCCC)CCCC
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Cl-]
Agent: [Li+]
Solvent: CN(C)C=O
Solvent: CCOCC
Product: C=CCc1cccc(Oc2ccccc2)c1

Procedure:
A suspension of 1-bromo-3-phenoxybenzene (2.01 g; 8.08 mmol), PdCl2(PPh3)2 (296 mg; 0.42 mmol), allyl tributyltin 3.13 g; 9.46 mmol), triphenylphosphine (455 mg; 1.73 mmol) and LiCl (1.39 g; 33 mmol) in 10 ml DMF was stirred at 100° C. for 3 h. After cooling to r.t the mixture was diluted with Et2O (75 ml), washed with water (3×50 ml) and brine, dried over MgSO4 and concentrated. Flash chromatography with hexane afforded the desired material.
Reaction SMILES: [O:1]1[C:5](=[O:6])[CH2:4][CH:3]2[CH2:7][CH2:8][CH2:9][CH:2]12.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[CH2:20](Br)[CH:21]=[CH2:22]>C1COCC1>[CH2:22]([CH:4]1[C:5](=[O:6])[O:1][CH:2]2[CH2:9][CH2:8][CH2:7][CH:3]12)[CH:21]=[CH2:20]
Reactant: C=CCBr
Reactant: O=C1CC2CCCC2O1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: C1CCOC1
Product: C=CCC1C(=O)OC2CCCC21

Procedure:
Analogously to the procedure of Example 1, the title compound is was prepared from 1.2 g (9.5 nmuol) of hexahydro-cyclopenta[b]furan-2-one, 10 ml of 1 molar lithium bis-(trimethylsilyl)-amide solution in THF and 1.29 g (9.5 mmol) of allyl bromide in 20 ml of THF. Yield: 1.25 g (79%) of a colourless oil. 1H-NMR(200 MHz; [d6]-DMSO): δ[ppm]: 1.47-1.89 (br m,6H), 2.15-2.55 (br m,4H), 4.41 (m,1H), 5.12 (dd,1H), 5.18 (dd,1H), 5.76 (ddt,1H)
Reaction SMILES: [CH3:1][C:2]1([CH3:10])[O:6][CH:5]([CH2:7][CH2:8][OH:9])[CH2:4][O:3]1>ClCCl>[CH3:1][C:2]1([CH3:10])[O:6][CH:5]([CH2:7][CH:8]=[O:9])[CH2:4][O:3]1
Reactant: CC1(C)OCC(CCO)O1
Solvent: ClCCl
Product: CC1(C)OCC(CC=O)O1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
A solution of 2-(2,2-dimethyl-1,3-dioxolan-4-yl)ethanol (530 mg, ALD) in dichloromethane (50 ml) was added with Dess-Martin periodinane[1,1,1-triacetoxy-1,1-dihydro-1,2-benziodoxol-3(1H)-one] (2.23 g, LANC), and the mixture was stirred at room temperature for 2 hours. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel chromatography (flash column chromatography, hexane:ethyl acetate=2:1) to obtain the title compound (Intermediate ia-03).
Reaction SMILES: [CH2:1]([C:5]1[N:6]([CH2:22][C:23]2[CH:32]=[CH:31][C:26]([C:27]([O:29][CH3:30])=[O:28])=[CH:25][CH:24]=2)[C:7](/[CH:10]=[C:11]2\[NH:12][C:13](=[O:21])[N:14]([CH2:17][CH2:18][CH2:19][CH3:20])[C:15]\2=[O:16])=[CH:8][N:9]=1)[CH2:2][CH2:3][CH3:4].C([O-])([O-])=O.[K+].[K+].[ClH:39].[NH2:40][C:41]1[S:42][CH:43]=[C:44]([CH2:46][Cl:47])[N:45]=1.Cl>CN(C=O)C.CCOCC>[ClH:47].[ClH:39].[CH2:1]([C:5]1[N:6]([CH2:22][C:23]2[CH:32]=[CH:31][C:26]([C:27]([O:29][CH3:30])=[O:28])=[CH:25][CH:24]=2)[C:7](/[CH:10]=[C:11]2\[N:12]([CH2:46][C:44]3[N:45]=[C:41]([NH2:40])[S:42][CH:43]=3)[C:13](=[O:21])[N:14]([CH2:17][CH2:18][CH2:19][CH3:20])[C:15]\2=[O:16])=[CH:8][N:9]=1)[CH2:2][CH2:3][CH3:4]
Reactant: CCCCc1ncc(/C=C2\NC(=O)N(CCCC)C2=O)n1Cc1ccc(C(=O)OC)cc1
Reactant: Nc1nc(CCl)cs1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOCC
Solvent: CN(C)C=O
Product: CCCCc1ncc(/C=C2/C(=O)N(CCCC)C(=O)N2Cc2csc(N)n2)n1Cc1ccc(C(=O)OC)cc1
Reaction time: 48 h

Procedure:
To a solution of methyl Z-4-[[2-butyl-5-[(1-butyl-2,5-dioxo-4-imidazolidinylidene) methyl]-1H-imidazol-1-yl]methyl]benzoate (0.569 g, 1.2 mmol) in DMF (5 mL) is added K2CO3 (2.0 g, 15 mmol). After stirring for 5 minutes 2-amino-4-chloromethylthiazole hydrochloride (0.222 g, 1.2 mmol) is added. The mixture is stirred for 48 hours and the filtered. The filtrate is concentrated in vacuo and dissolved in methylene chloride (30 mL). This solution is washed with water and drived over K2CO3 and charcoal. A viscous oil is obtained by evaporation of the solvents in vacuo. This oil is dissolved in ether and treated with ethereal HCl to precipitate a gum which is collected by decantation. This gum is recrystallized from 2-propanol/ether.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH2:8])=[C:4]([C:9]([CH3:12])([CH3:11])[CH3:10])[CH:3]=1.[H-].[Na+].Br[CH2:16][CH2:17][CH2:18][CH2:19]Br>>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:19][CH2:18][CH2:17][CH2:16]2)=[C:4]([C:9]([CH3:12])([CH3:11])[CH3:10])[CH:3]=1
Reactant: BrCCCCBr
Reactant: CC(C)(C)c1cc(Br)ccc1N
Agent: [H-]
Agent: [Na+]
Product: CC(C)(C)c1cc(Br)ccc1N1CCCC1
Yield: 61.2 %

Procedure:
In a manner analogous to example 1 b, the process is carried out by a reaction of 10 g (44 mmol) of 4-bromo-2-tert-butylphenylamine with 3.8 g (96 mmol) of 60% sodium hydride and with 3.4 ml (96 mmol) of 1,4-dibromobutane. 7.6 g of 1-(4-bromo-2-tert-butylphenyl)-pyrrolidine are obtained in the form of an oil (yield=61%).
Reaction SMILES: [H-].[Na+].[CH2:3]([OH:6])[CH2:4][OH:5].Cl[C:8]1[C:9]2[C:16]([C:17]3[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=3)=[C:15]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[O:14][C:10]=2[N:11]=[CH:12][N:13]=1>CN(C=O)C.O>[CH3:24][O:23][C:20]1[CH:19]=[CH:18][C:17]([C:16]2[C:9]3[C:8]([O:5][CH2:4][CH2:3][OH:6])=[N:13][CH:12]=[N:11][C:10]=3[O:14][C:15]=2[C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=2)=[CH:22][CH:21]=1
Reactant: OCCO
Reactant: COc1ccc(-c2c(-c3ccccc3)oc3ncnc(Cl)c23)cc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: COc1ccc(-c2c(-c3ccccc3)oc3ncnc(OCCO)c23)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 75.8 %

Procedure:
Add, at 0° C., 59 mg (1.5 mmol) of 60% sodium hydride to a solution of 461 mg (7.4 mmol) ethylene glycol in 10 ml DMF. After warming to room temperature, continue stirring for 1 h. Then add 0.50 g (1.5 mmol) 4-chloro-5-(4-methoxyphenyl)-6-phenylfuro[2,3-d]pyrimidine and stir the mixture for 3 h at room temperature. Next, dilute with water and extract with ethyl acetate. Wash the organic phase with saturated sodium chloride solution, dry over magnesium sulphate and concentrate by evaporation. The raw product thus obtained is purified by RP-HPLC (column: Gromsil 250 mm×30 mm, 10 μm; acetonitrile/water gradient: 0-3 min 5% acetonitrile, 3-50 min 5%→98% acetonitrile, 50-55 min 98% acetonitrile). In this way, 412 mg (77% of theor.) 2-{[5-(4-methoxyphenyl)-6-phenylfuro[2,3-d]pyrimidin-4-yl]oxy}ethanol is obtained.
Reaction SMILES: F[C:2]1[CH:16]=[CH:15][CH:14]=[CH:13][C:3]=1[C:4]([N:6]1[CH2:10][CH2:9][N:8]=[C:7]1SC)=[O:5].[NH2:17][N:18]1[CH2:22][CH2:21][CH2:20][CH2:19]1>>[N:18]1([N:17]2[C:2]3[C:3](=[CH:13][CH:14]=[CH:15][CH:16]=3)[C:4](=[O:5])[N:6]3[CH2:10][CH2:9][N:8]=[C:7]23)[CH2:22][CH2:21][CH2:20][CH2:19]1
Reactant: CSC1=NCCN1C(=O)c1ccccc1F
Reactant: NN1CCCC1
Product: O=C1c2ccccc2N(N2CCCC2)C2=NCCN12

Procedure:
When the procedure of Example 2 is repeated using the product of Example 1 and N-aminopyrrolidine, the product obtained is 2,10-dihydro-10-(1-pyrrolidinyl)imidazo[2,1-b]quinazolin-4(3H)-one.
Reaction SMILES: C([Li])CCC.[F:6][C:7]1[CH:16]=[CH:15][C:10]2[CH2:11][CH2:12][CH2:13][O:14][C:9]=2[CH:8]=1.[C:17](=[O:19])=[O:18].C(OCC)C>O1CCCC1>[F:6][C:7]1[CH:16]=[CH:15][C:10]2[CH2:11][CH2:12][CH2:13][O:14][C:9]=2[C:8]=1[C:17]([OH:19])=[O:18]
Reactant: Fc1ccc2c(c1)OCCC2
Reactant: O=C=O
Agent: [Li]CCCC
Solvent: CCOCC
Solvent: C1CCOC1
Product: O=C(O)c1c(F)ccc2c1OCCC2
Temperature: -78 °C

Procedure:
A stirred solution of 30.4 mL (0.076 mole) of n-butyllithium (2.5M in hexanes) in 200 mL of tetrahydrofuran was cooled to -78 °C., and 10.5 grams (0.069 mole) of 3,4-dihydro-7-fluoro-2H-1-benzopyran was added portionwise. Upon completion of the addition, the reaction mixture was maintained at -78° C. for 30 minutes. The reaction mixture was then exposed to a carbon dioxide atmosphere for 18 hours. The reaction mixture was then stirred with diethyl ether and extracted with an aqueous 5% sodium hydroxide solution. The basic layer was washed with diethyl ether, made acidic with concentrated hydrochloric acid, and then extracted with diethyl ether. The extract was dried with magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure, yielding 10.2 grams of 3,4-dihydro-7-fluoro-2H-1-benzopyran-8-ylcarboxylic acid. The NMR spectrum was consistent with the proposed structure.
Reaction SMILES: [CH2:1]([N:3]([CH2:24][CH3:25])[CH2:4][CH2:5][N:6]1[C:14]2[CH:13]=[CH:12][C:11]([CH2:15][NH2:16])=[C:10]3[S:17][C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=4[C:8]([C:9]=23)=[N:7]1)[CH3:2].CCCCCC.C[CH2:33][O:34]C(C)=O.CCOC(C)=O.CC(O)C>C(Cl)Cl>[CH2:24]([N:3]([CH2:1][CH3:2])[CH2:4][CH2:5][N:6]1[C:14]2[CH:13]=[CH:12][C:11]([CH2:15][NH2:16])=[C:10]3[S:17][C:18]4[CH:23]=[CH:22][C:21]([O:34][CH3:33])=[CH:20][C:19]=4[C:8]([C:9]=23)=[N:7]1)[CH3:25]
Reactant: CCN(CC)CCn1nc2c3c(c(CN)ccc31)Sc1ccccc1-2
Reactant: CCOC(C)=O
Solvent: CC(C)O
Solvent: ClCCl
Solvent: CCCCCC
Product: CCN(CC)CCn1nc2c3c(c(CN)ccc31)Sc1ccc(OC)cc1-2
Yield: 90 %

Procedure:
The compound is prepared via the same procedure used to synthesize the compound of Example 8. Pure material is obtained by flash chromatography [hexane:EtOAc (50:50), EtOAc, CH2Cl2, 0.5-1% IPA in CH2Cl2 ] in 90% yield: mp 74°-76° C. 1H NMR (CDCl3) 0.96 (6H; t), 2.52 (4H; q), 2.88 (2H; t), 3.72 (2H; s), 3.82 (3H; s), 4.28 (2H; t), 6.70-6.80 (2H; m), 7.10 (1H; d), 7.62 (1H; d)ppm. MS m/z 383 (MH+). Anal (C21H26N4OS) C, H, N.
Reaction SMILES: CS(O[CH2:6][CH2:7][CH:8]1[CH2:14][CH2:13][C:12]2[C:15]([O:25][CH3:26])=[C:16]([O:23][CH3:24])[C:17]([O:21][CH3:22])=[C:18]([O:19][CH3:20])[C:11]=2[CH2:10][CH2:9]1)(=O)=O.[I-:27].[Na+].CC(C)=O>O>[I:27][CH2:6][CH2:7][CH:8]1[CH2:14][CH2:13][C:12]2[C:15]([O:25][CH3:26])=[C:16]([O:23][CH3:24])[C:17]([O:21][CH3:22])=[C:18]([O:19][CH3:20])[C:11]=2[CH2:10][CH2:9]1
Reactant: [I-]
Reactant: COc1c2c(c(OC)c(OC)c1OC)CCC(CCOS(C)(=O)=O)CC2
Agent: [Na+]
Solvent: CC(C)=O
Solvent: O
Product: COc1c2c(c(OC)c(OC)c1OC)CCC(CCI)CC2
Yield: 97.5 %

Procedure:
The mixture of 2-(1,2,3,4-tetramethoxy-6,7,8,9-tetrahydro-5H-benzo[a]cyclohepten-7-yl)ethyl methanesulfonate (3.12 g), sodium iodide (3.61 g), and acetone (40 ml) was heated under reflux for 1 hr. The reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed with 5% aqueous sodium sulfite, water, and saturated aqueous sodium chloride, and dried. The solvent was removed in vacuo to yield the entitled compound (3.29 g) as crystals.
Reaction SMILES: [CH2:1]([O:4][N:5]([C@H:18]1[CH2:23][NH:22][C@H:21]([C:24]([NH2:26])=[O:25])[C:20]([CH:27]2[CH2:29][CH2:28]2)=[CH:19]1)S(C1C=CC=CC=1[N+]([O-])=O)(=O)=O)[CH:2]=[CH2:3].C(ON[C@@H]1C(C)=C[C@@H](CO[Si](C(C)(C)C)(C)C)NC1)C=C>>[CH2:1]([O:4][NH:5][CH:18]1[CH2:23][NH:22][C@@H:21]([C:24]([NH2:26])=[O:25])[C:20]([CH:27]2[CH2:28][CH2:29]2)=[CH:19]1)[CH:2]=[CH2:3]
Reactant: C=CCON([C@@H]1C=C(C2CC2)[C@@H](C(N)=O)NC1)S(=O)(=O)c1ccccc1[N+](=O)[O-]
Agent: C=CCON[C@H]1CN[C@H](CO[Si](C)(C)C(C)(C)C)C=C1C
Product: C=CCONC1C=C(C2CC2)[C@H](C(N)=O)NC1

Procedure:
The title compound was prepared from (2S,5R)-5-(N-(allyloxy)-2-nitrophenylsulfonamido)-3-cyclopropyl-1,2,5,6-tetrahydropyridine-2-carboxamide (Intermediate 243, 0.518 g, 1.23 mmol) following the procedure described for Intermediate 12. The desired product was obtained as a light yellow oil (0.171 g, 59%). The product is a mixture of diastereomers.
Reaction SMILES: [Si:1]([O:8][C@@H:9]1[C@@:28]2([CH3:29])[C:13](=[CH:14][CH:15]=[C:16]3[C@@H:27]2[CH2:26][CH2:25][C@@:24]2([CH3:30])[C@H:17]3[CH2:18][CH:19]=[C:20]2[C@H:21]([OH:23])[CH3:22])[CH2:12][C@@H:11]([O:31][Si:32]([C:35]([CH3:38])([CH3:37])[CH3:36])([CH3:34])[CH3:33])[CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[H-].[Na+].Br[CH2:42]/[CH:43]=[CH:44]/[C:45]([CH2:56][CH3:57])([O:48][Si:49]([CH2:54][CH3:55])([CH2:52][CH3:53])[CH2:50][CH3:51])[CH2:46][CH3:47]>O1CCCC1>[Si:1]([O:8][C@@H:9]1[C@@:28]2([CH3:29])[C:13](=[CH:14][CH:15]=[C:16]3[C@@H:27]2[CH2:26][CH2:25][C@@:24]2([CH3:30])[C@H:17]3[CH2:18][CH:19]=[C:20]2[C@H:21]([O:23][CH2:42]/[CH:43]=[CH:44]/[C:45]([CH2:56][CH3:57])([O:48][Si:49]([CH2:54][CH3:55])([CH2:50][CH3:51])[CH2:52][CH3:53])[CH2:46][CH3:47])[CH3:22])[CH2:12][C@@H:11]([O:31][Si:32]([C:35]([CH3:37])([CH3:36])[CH3:38])([CH3:33])[CH3:34])[CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]
Reactant: CCC(/C=C/CBr)(CC)O[Si](CC)(CC)CC
Reactant: C[C@@H](O)C1=CC[C@H]2C3=CC=C4C[C@@H](O[Si](C)(C)C(C)(C)C)C[C@H](O[Si](C)(C)C(C)(C)C)[C@]4(C)[C@H]3CC[C@]12C
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CCC(/C=C/CO[C@H](C)C1=CC[C@H]2C3=CC=C4C[C@@H](O[Si](C)(C)C(C)(C)C)C[C@H](O[Si](C)(C)C(C)(C)C)[C@]4(C)[C@H]3CC[C@]12C)(CC)O[Si](CC)(CC)CC
Yield: 72.9 %

Procedure:
Under the same conditions as in Example 83, 1α,3β-bis(tert-butyldimethylsilyloxy)-20(R)-hydroxypregna-5,7,16-triene (60.0 mg, 0.107 mmol), sodium hydride (60%, 17.1 mg, 0.428 mmol), 15-crown-5(10 μl) and (E)-1-bromo-4-ethyl-4-triethylsilyloxy-2-hexene (134 mg, 0.420 mmol) were reacted in tetrahydrofuran (1 ml) and worked up, and then the residue was purified by preparative thin layer chromatography (0.5 mm×2, hexane:ethyl acetate=40:1, developed once) to give the title compound as a colorless oil (62.4 mg, 73%).
Reaction SMILES: [S:1]1[CH:5]=[CH:4][N:3]=[C:2]1[C:6]([C:8]1[CH:13]=[C:12]([O:14][CH2:15][C:16]2[CH:25]=[CH:24][C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[CH:17]=2)[CH:11]=[C:10]([O:26][CH3:27])[CH:9]=1)=[O:7].[CH2:28](OCC)[CH3:29].C([Mg]I)C.[Cl-].[NH4+]>O1CCCC1>[OH:7][C:6]([C:2]1[S:1][CH:5]=[CH:4][N:3]=1)([C:8]1[CH:13]=[C:12]([O:14][CH2:15][C:16]2[CH:25]=[CH:24][C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[CH:17]=2)[CH:11]=[C:10]([O:26][CH3:27])[CH:9]=1)[CH2:28][CH3:29]
Reactant: COc1cc(OCc2ccc3ccccc3c2)cc(C(=O)c2nccs2)c1
Reactant: CCOCC
Agent: CC[Mg]I
Agent: [Cl-]
Agent: [NH4+]
Solvent: C1CCOC1
Product: CCC(O)(c1cc(OC)cc(OCc2ccc3ccccc3c2)c1)c1nccs1
Yield: 55 %

Procedure:
A solution of the ketone so obtained (1.2 g) in tetrahydrofuran (20 ml) was added to a diethyl ether solution of ethylmagnesium iodide [prepared from iodoethane (0.6 ml) and magnesium turnings (0.154 g) under diethyl ether (10 ml)] and the mixture was heated to reflux for 15 minutes. The mixture was poured into a saturated aqueous ammonium chloride solution and extracted with ethyl acetate (3×15 ml). The combined extracts were washed with water, dried (MgSO4) and evaporated. The residue was purified by column chromatography eluting with methylene chloride/ethyl acetate (17/3 v/v) to give 2-[1-hydroxy-1-[3-methoxy-5-(naphth-2-ylmethoxy) phenyl]propyl]thiazole (0.72 g, 55%), m.p. 105° C. (recrystallised from a mixture of petrol (b.p. 60°-80° C.) and ethyl acetate).
Reaction SMILES: [C:1]([C:4]1[C:5]([C:10]([F:13])([F:12])[F:11])=[N:6][CH:7]=[N:8][CH:9]=1)(=[O:3])[CH3:2].B.[Na]>CO>[OH:3][CH:1]([C:4]1[C:5]([C:10]([F:13])([F:12])[F:11])=[N:6][CH:7]=[N:8][CH:9]=1)[CH3:2]
Reactant: CC(=O)c1cncnc1C(F)(F)F
Agent: B
Agent: [Na]
Solvent: CO
Product: CC(O)c1cncnc1C(F)(F)F
Reaction time: 0.5 h
Yield: 39.6 %

Procedure:
0.5 g of 5-acetyl-4-trifluoromethylpyrimidine was dissolved in 10 ml of dry methanol. 0.03 g of sodium boron hydride was added, and the mixture was stirred for 30 minutes under cooling with ice, and then further stirred overnight at room temperature. After the completion of the reaction, the solvent was distilled off, and 40 ml of a 1:1 solvent mixture of chloroform/water was added for chloroform extraction. After the chloroform layer was dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure. After purification by column chromatography, 0.2 g of the desired product was obtained as a viscous liquid. nD19.9 1.4549
Reaction SMILES: [H-].[Na+].[N:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[NH:9][C:10]([C:12]1[C:13]2[CH2:14][C@H:15]3[CH2:28][C@H:16]3[C:17]=2[N:18]([C:20]2[CH:25]=[CH:24][C:23]([F:26])=[CH:22][C:21]=2[F:27])[N:19]=1)=[O:11].I[CH3:30]>CN(C=O)C>[CH3:30][N:9]([C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][N:3]=1)[C:10]([C:12]1[C:13]2[CH2:14][C@H:15]3[CH2:28][C@H:16]3[C:17]=2[N:18]([C:20]2[CH:25]=[CH:24][C:23]([F:26])=[CH:22][C:21]=2[F:27])[N:19]=1)=[O:11]
Reactant: O=C(Nc1ccccn1)c1nn(-c2ccc(F)cc2F)c2c1C[C@H]1C[C@@H]21
Reactant: CI
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CN(C(=O)c1nn(-c2ccc(F)cc2F)c2c1C[C@H]1C[C@@H]21)c1ccccn1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 34.1 %

Procedure:
To a reaction vial containing NaH (2.3 mg, 0.057 mmol) was added (1aR,5aR)-2-(2,4-difluoro-phenyl)-1a,2,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid pyridin-2-ylamide (10 mg, 0.028 mmol) in DMF (0.5 mL) under nitrogen protection. After 15 min, iodomethane (2.7 μL, 0.043 mmol) in DMF (0.1 mL) was added. The reaction mixture was stirred at room temperature overnight, and then purified by preparative LCMS to give the title compound (3.5 mg). LCMS m/z=367.3 [M+H]+; 1H NMR (400 MHz, CDCl3) δ ppm 0.52 (td, J=4.7 and 3.4 Hz, 1H), 1.15-1.22 (m, 1H), 2.19-2.23 (m, 1H), 2.28-2.34 (m, 1H), 2.97 (dd, J=16.6 Hz, 1H), 3.08 (dd, J=16.4 and 6.3 Hz, 1H), 4.39 (s, 3H), 6.97-7.08 (m, 2H), 7.49 (t, J=6.6 Hz, 1H), 7.88-7.94 (m, 1H), 8.22 (t, J=8.0 Hz, 1H), 8.50-8.55 (m, 2H).
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4](Br)[CH:3]=1.[Li]CCCC.[CH3:14][Si:15](Cl)([CH3:17])[CH3:16].O>CCOCC>[Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Si:15]([CH3:17])([CH3:16])[CH3:14])[CH:3]=1
Reactant: C[Si](C)(C)Cl
Reactant: Brc1cccc(Br)c1
Agent: [Li]CCCC
Solvent: CCOCC
Solvent: O
Product: C[Si](C)(C)c1cccc(Br)c1
Reaction time: 0.5 h
Yield: 95.7 %

Procedure:
To a solution of 10 g (42.39 mmol) of 1,3-dibromobenzene in 80 mL of anhydrous Et2O, cooled to −78° C. and maintained under a nitrogen atmosphere, are added dropwise with stirring, over 30 minutes, 26.49 mL (42.39 mmol) of a solution of BuLi (1.5M/hexane). After stirring for a further 30 minutes at −78° C., 5.96 mL (46.63 mmol) of TMSCl are added dropwise to the reaction mixture. Stirring is maintained at this temperature for 90 minutes and the reaction mixture is then hydrolysed by adding 15 mL of water. The product is extracted with ethyl acetate (3×50 mL). The combined organic phases are washed with saturated aqueous NaCl solution (2×25 mL), dried over Na2SO4, filtered and evaporated under reduced pressure. The crude reaction product is purified by chromatography on a column of silica gel, eluting with heptane, to give 9.3 g of the expected 1-bromo-3-trimethylsilylbenzene, in the form of a colourless oil.
Reaction SMILES: [OH:1][CH2:2][C@H:3]1[O:8][C:7]([CH3:10])([CH3:9])[O:6][C@@H:5]([CH2:11][C:12]([O:14]C(C)(C)C)=[O:13])[CH2:4]1.[OH-].[Na+]>O1CCCC1>[OH:1][CH2:2][C@H:3]1[O:8][C:7]([CH3:9])([CH3:10])[O:6][C@@H:5]([CH2:11][C:12]([OH:14])=[O:13])[CH2:4]1
Reactant: CC(C)(C)OC(=O)C[C@H]1C[C@@H](CO)OC(C)(C)O1
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Product: CC1(C)O[C@H](CO)C[C@H](CC(=O)O)O1

Procedure:
Mixture of tert-butyl 2-((4R,6S)-6-(hydroxymethyl)-2,2-dimethyl-1,3-dioxan-4-yl)acetate (200 grams), sodium hydroxide (62 grams) in tetrahydrofuran (400 ml) was heated to reflux temperature and stirred up to completion of the reaction. The solvent from the reaction mixture was distilled off completely under reduced pressure at below 70° C. to get the title compound.
Reaction SMILES: C([O:4][C@H:5]1[CH2:22][CH2:21][C@@:20]2([CH2:23][O:24][C:25](=[O:27])[CH3:26])[C:7](=[CH:8][CH2:9][C@@H:10]3[C@@H:19]2[CH2:18][CH2:17][C@@:15]2([CH3:16])[C@H:11]3[CH2:12][CH2:13][C@@H:14]2[O:28][C:29](=[O:31])[CH3:30])[CH2:6]1)(=O)C.C(O)(=O)C.C(O)(=O)C.O[C@H]1CC[C@@]2(CO)C(=CC[C@@H]3[C@@H]2CC[C@@]2(C)[C@H]3CCC2=O)C1>>[C:29]([O:28][C@H:14]1[CH2:13][CH2:12][C@H:11]2[C@H:10]3[C@H:19]([CH2:18][CH2:17][C@:15]12[CH3:16])[C@:20]1([CH2:23][O:24][C:25](=[O:27])[CH3:26])[C:7]([CH2:6][C@@H:5]([OH:4])[CH2:22][CH2:21]1)=[CH:8][CH2:9]3)(=[O:31])[CH3:30]
Reactant: CC(=O)OC[C@]12CC[C@H](OC(C)=O)CC1=CC[C@@H]1[C@@H]2CC[C@]2(C)[C@@H](OC(C)=O)CC[C@@H]12
Agent: C[C@]12CC[C@H]3[C@@H](CC=C4C[C@@H](O)CC[C@@]43CO)[C@@H]1CCC2=O
Solvent: CC(=O)O
Product: CC(=O)OC[C@]12CC[C@H](O)CC1=CC[C@@H]1[C@@H]2CC[C@]2(C)[C@@H](OC(C)=O)CC[C@@H]12

Procedure:
Substituting 5-androstene-3β,17β,19-triol triacetate for the 3β,19-dihydroxy-5-androsten-17-one diacetate above results in the preparation of 5-androstene-3β,17β,19-triol 17,19-diacetate.