Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: FC([Si:5]([CH3:8])([CH3:7])[CH3:6])(F)F.[Si:9]([O:16][C@H:17]1[CH2:22][CH2:21][C@H:20]2[C@@:23]3([CH:48]=[CH2:49])[C@H:32]([C@@H:33]([CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][C:40](=[O:45])[C:41]([F:44])([F:43])[F:42])[CH2:34][C@:18]12[CH3:19])[C:31]1[CH:30]=[CH:29][C:28]([O:46][CH3:47])=[CH:27][C:26]=1[CH2:25][CH2:24]3)(C(C)(C)C)([CH3:11])[CH3:10]>>[C:18]([C@H:19]1[CH2:22][CH2:21][C@H:20]2[C@@:23]3([CH:48]=[CH2:49])[C@H:32]([C@@H:33]([CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][C:40]([C:41]([F:44])([F:43])[F:42])([O:45][Si:5]([CH3:6])([CH3:7])[CH3:8])[C:41]([F:42])([F:44])[F:43])[CH2:34][C@:18]12[CH2:17][O:16][SiH:9]([CH3:10])[CH3:11])[C:31]1[CH:30]=[CH:29][C:28]([O:46][CH3:47])=[CH:27][C:26]=1[CH2:25][CH2:24]3)([CH3:20])([CH3:19])[CH3:17]
Reactant: C[Si](C)(C)C(F)(F)F
Reactant: C=C[C@@]12CCc3cc(OC)ccc3[C@H]1[C@@H](CCCCCC(=O)C(F)(F)F)C[C@]1(C)[C@@H](O[Si](C)(C)C(C)(C)C)CC[C@H]12
Product: C=C[C@@]12CCc3cc(OC)ccc3[C@H]1[C@@H](CCCCCC(O[Si](C)(C)C)(C(F)(F)F)C(F)(F)F)C[C@]1(CO[SiH](C)C)[C@@H](C(C)(C)C)CC[C@@H]21

Procedure:
In the reaction with (trifluoromethyl)-trimethylsilane analogously to instructions 1.1, 131 mg of alcohol 16b yields 162 mg of trimethylsilyl ether 17b as a yellow, viscous mass (GC-MS: m/z theor.: 734, pract.: 734). The latter is, without performing the reaction with tetrabutylammonium fluoride-trihydrate, used in the next stage.
Reaction SMILES: [C:1]([C:5]1[CH:17]=[CH:16][C:8]([O:9][CH:10]([CH2:14][CH3:15])[C:11]([OH:13])=[O:12])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[O:18]([C@H:26]1[CH2:35][C@H:34](O)[C@H:33]2[C:28]([CH:29]=[CH:30][C@H:31]([CH3:54])[C@@H:32]2[CH2:37][CH2:38][C@H:39]2[O:44][C:43](=[O:45])[CH2:42][C@H:41]([O:46][Si:47]([C:50]([CH3:53])([CH3:52])[CH3:51])([CH3:49])[CH3:48])[CH2:40]2)=[CH:27]1)[Si:19]([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:21])[CH3:20]>>[Si:19]([O:18][C@H:26]1[CH2:35][C@H:34]([O:12][C:11](=[O:13])[CH:10]([O:9][C:8]2[CH:16]=[CH:17][C:5]([C:1]([CH3:2])([CH3:4])[CH3:3])=[CH:6][CH:7]=2)[CH2:14][CH3:15])[C@H:33]2[C:28]([CH:29]=[CH:30][C@H:31]([CH3:54])[C@@H:32]2[CH2:37][CH2:38][C@H:39]2[O:44][C:43](=[O:45])[CH2:42][C@H:41]([O:46][Si:47]([C:50]([CH3:53])([CH3:52])[CH3:51])([CH3:48])[CH3:49])[CH2:40]2)=[CH:27]1)([C:22]([CH3:23])([CH3:24])[CH3:25])([CH3:21])[CH3:20]
Reactant: CCC(Oc1ccc(C(C)(C)C)cc1)C(=O)O
Reactant: C[C@H]1C=CC2=C[C@@H](O[Si](C)(C)C(C)(C)C)C[C@H](O)[C@@H]2[C@H]1CC[C@@H]1C[C@@H](O[Si](C)(C)C(C)(C)C)CC(=O)O1
Product: CCC(Oc1ccc(C(C)(C)C)cc1)C(=O)O[C@H]1C[C@H](O[Si](C)(C)C(C)(C)C)C=C2C=C[C@H](C)[C@H](CC[C@@H]3C[C@@H](O[Si](C)(C)C(C)(C)C)CC(=O)O3)[C@H]21
Yield: 101 %

Procedure:
A procedure similar to that described in Example 1, above, was followed, but using 803 mg of (2RS)-2-(4-t-butylphenoxy)butyric acid and 1.0 g of (4R,6R)-6-{(1S,2S,6S,8S,8aR)-2-[1,2,6,7,8,8a-hexahydro-6-t-butyldimethylsiloxy-8-hydroxy-2-methyl-1-naphthyl]ethyl}tetrahydro-4-t-butyldimethylsilyloxy-2H-pyran-2-one [prepared as described in Example B, above], to give 1.41g of the title compound as a colorless foam.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:4]=1[C:5]([NH:12][CH2:13][C:14]([CH3:22])([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[CH3:15])=[N:6][NH:7]2.C(=O)([O-])[O-].[K+].[K+].Br[CH:30]([CH3:32])[CH3:31].FC1C=CC=C(OC)C=1C=O.CO.O.C(O)(C(F)(F)F)=O>CN(C=O)C>[CH:30]([N:7]1[C:8]2[C:4](=[C:3]([O:2][CH3:1])[CH:11]=[CH:10][CH:9]=2)[C:5]([NH:12][CH2:13][C:14]([CH3:22])([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH3:15])=[N:6]1)([CH3:32])[CH3:31]
Reactant: COc1cccc2[nH]nc(NCC(C)(C)c3ccccc3)c12
Reactant: CC(C)Br
Agent: COc1cccc(F)c1C=O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O=C(O)C(F)(F)F
Solvent: CN(C)C=O
Solvent: CO
Product: COc1cccc2c1c(NCC(C)(C)c1ccccc1)nn2C(C)C
Temperature: 100 °C

Procedure:
To a stirred solution of Example 42 (16 mg, 0.054 mmol) in DMF (0.5 mL) was added potassium carbonate (8.3 mg, 0.06 mmol) followed by 2-bromopropane (18 uL, 0.12 mmol). Upon completion of addition, the reaction mixture was heated at 100° C. for 6 h. At the conclusion of this period, the reaction mixture was subjected to preparative HPLC (Rt=7.76 minutes using YMC ODS 5u 30×100 mm column with flow rate of 40 mL/min over 10 min period; 20 to 100% Solvent B. Solvent A=10/90/0.1% MeOH/H2O/TFA. Solvent B=90/10/0.1%) to provide Example 43 as a pink film (1.3 mg, 7%). 1H NMR (500 MHz, CDCl3) δ ppm 1.44 (s, 6H), 1.45 (s, 3H), 1.47 (s, 3H), 3.56 (s, 2H), 3.69 (s, 3H), 6.14 (d, J=7.70 Hz, 1H), 6.73 (d, J=8.80 Hz, 1H), 7.09 (t, J=7.97 Hz, 1H), 7.21-7.24 (m, 1H), 7.35 (t, J=7.70 Hz, 2H), 7.47 (d, J=8.25 Hz, 2H).
Reaction SMILES: C([Li])CCC.[CH:6]1[CH:11]=[CH:10][C:9]([CH2:12][C:13]2[C:18](Br)=[CH:17][CH:16]=[CH:15][CH:14]=2)=[CH:8][CH:7]=1.[O:20]1[C:24]2([CH2:29][CH2:28][C:27](=[O:30])[CH2:26][CH2:25]2)[O:23][CH2:22][CH2:21]1>CCCCCC.C1COCC1>[C:9]1([CH2:12][C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][C:18]=2[C:27]2([OH:30])[CH2:28][CH2:29][C:24]3([O:23][CH2:22][CH2:21][O:20]3)[CH2:25][CH2:26]2)[CH:10]=[CH:11][CH:6]=[CH:7][CH:8]=1
Reactant: O=C1CCC2(CC1)OCCO2
Reactant: Brc1ccccc1Cc1ccccc1
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CCCCCC
Product: OC1(c2ccccc2Cc2ccccc2)CCC2(CC1)OCCO2
Reaction time: 1 h
Yield: 42.3 %

Procedure:
26.25 ml of 2.4 molar solution of n-butyllithium in n-hexane is added dropwise with stirring at -50° to -40° C. under dry nitrogen to a solution of 10.87 g of 2-bromodiphenylmethane in 25 ml of dry THF. The mixture is stirred at -50° to -40° C. for one hour after addition is completed. A solution of 6.30 g of 1,4-dioxaspiro(4.5)decan-8-one in 20 ml of dry THF is added dropwise at -50° to -40° C. This mixture is stirred overnight (16 hours) at -70° C. to +10° C., and quenched with 50 ml of water. The organic phase is diluted with 100 ml of ether and washed three times with 50 ml portions of water. The aqueous phase and the washing water are extracted with 100 ml of CH2Cl2, which is washed twice with 50 ml portions of water. The combined organic phases are dried over Na2SO4 and evaporated to an oil. This oil is treated with ether/hexane (20 ml/50 ml) mixture to give 6.0 g (45.8%) yield of crystalline product which is recrystallized from ether/hexane (10 ml/40 ml) to provide 5.53 g (42.2% yield) of 8-[2-(phenylmethyl)phenyl]-1,4-dioxaspiro(4.5)decan-8-ol, m.p. 97°-98° C.
Reaction SMILES: [CH3:1][C:2]1[S:6][C:5]([C:7]2[N:8]=[C:9]3[N:13]([C:14]=2[CH2:15][C:16](O)=[O:17])[C:12]2[CH:19]=[CH:20][CH:21]=[CH:22][C:11]=2[S:10]3)=[CH:4][CH:3]=1.[NH3:23]>O1CCCC1>[CH3:1][C:2]1[S:6][C:5]([C:7]2[N:8]=[C:9]3[N:13]([C:14]=2[CH2:15][C:16]([NH2:23])=[O:17])[C:12]2[CH:19]=[CH:20][CH:21]=[CH:22][C:11]=2[S:10]3)=[CH:4][CH:3]=1
Reactant: N
Reactant: Cc1ccc(-c2nc3sc4ccccc4n3c2CC(=O)O)s1
Solvent: C1CCOC1
Product: Cc1ccc(-c2nc3sc4ccccc4n3c2CC(N)=O)s1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
1.6 g (0.005 mole) of 2-(5-methylthien-2-yl)imidazo[2,1-b]-benzothiazole-3-acetic acid are treated, at room temperature, with 0.85 g (0.005 mole) of N,N'-carbonyldiimidazole in 30 ml of anhydrous tetrahydrofuran for 3 h 30 min. The mixture is cooled using an ice bath, an excess of ammonia in 10 ml of anhydrous tetrahydrofuran cooled to -10° C. is added, and the mixture is stirred for 4 h at room temperature. The solvent is evaporated under reduced pressure, the solid is collected by filtration, it is washed with water up to neutral pH, then with ethanol, and finally with ethyl ether. After recrystallization from methanol, 1 g of a beige compound is obtained. Melting point: 243°-245° C.
Reaction SMILES: OCCNCCO.[OH:8][CH:9]([CH2:17][OH:18])[CH2:10][NH:11][CH2:12][CH:13]([OH:16])[CH2:14][OH:15].BrCC(OC)=O.Br[CH:26]([CH:31]([CH3:33])[CH3:32])[C:27]([O:29]C)=[O:28]>>[OH:16][CH:13]([CH2:14][OH:15])[CH2:12][N:11]([CH:26]([CH:31]([CH3:33])[CH3:32])[C:27]([OH:29])=[O:28])[CH2:10][CH:9]([OH:8])[CH2:17][OH:18]
Reactant: OCC(O)CNCC(O)CO
Reactant: COC(=O)C(Br)C(C)C
Agent: COC(=O)CBr
Solvent: OCCNCCO
Product: CC(C)C(C(=O)O)N(CC(O)CO)CC(O)CO

Procedure:
By conducting the procedure described in Example 1, except that the bis-(2-hydroxyethyl)amine is replaced by an equimolar quantity of bis-(2,3-dihydroxypropyl)amine and the methyl bromoacetate is replaced by an equimolar quantity of methyl 2-bromoisovalerate, there is obtained 2-[N,N-bis-(2,3-dihydroxypropyl)amino]isovaleric acid.
Reaction SMILES: Br.[NH2:2][CH:3]1[CH2:7][C:6](=[O:8])[N:5]([C:9]2[CH:14]=[C:13]([Cl:15])[CH:12]=[C:11]([Cl:16])[CH:10]=2)[C:4]1=[O:17].C(N(CC)CC)C.[C:25](Cl)(=O)/[CH:26]=[CH:27]/[CH3:28]>O1CCCC1>[CH2:25]([NH:2][CH:3]1[CH2:7][C:6](=[O:8])[N:5]([C:9]2[CH:10]=[C:11]([Cl:16])[CH:12]=[C:13]([Cl:15])[CH:14]=2)[C:4]1=[O:17])[CH:26]=[CH:27][CH3:28]
Reactant: C/C=C/C(=O)Cl
Reactant: NC1CC(=O)N(c2cc(Cl)cc(Cl)c2)C1=O
Agent: Br
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: CC=CCNC1CC(=O)N(c2cc(Cl)cc(Cl)c2)C1=O
Temperature: 25 °C
Reaction time: 12 h

Procedure:
To 13.6 g of 3-amino-1-(3,5-dichlorophenyl)pyrrolidine-2,5-dione hydrobromide in 100 ml of tetrahydrofurane are added, at 0° C., 12 ml of triethylamine. Then 6 ml of crotonyl chloride are added dropwise and the reaction mixture is stirred for a further 12 hours at room temperature. The solution is then filtered and the filtrate is concentrated. The residue is purified by column chromatography over silica gel with dichloromethane/petroleum ether (85:15) as eluant. The solvent is removed and the residue is recrystallised from ethyl acetate/petroleum ether. The colourless crystals melt at 107°-110° C.
Reaction SMILES: [CH2:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10]([F:13])([F:12])[F:11])=[CH:6][C:5]=1[OH:14])[CH:2]=[CH2:3].[Cl:15][SiH:16](Cl)[Cl:17]>ClC(Cl)=C(Cl)Cl>[CH2:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10]([F:12])([F:13])[F:11])=[CH:6][C:5]=1[O:14][SiH:16]([Cl:17])[Cl:15])[CH:2]=[CH2:3]
Reactant: C=CCc1ccc(C(F)(F)F)cc1O
Reactant: Cl[SiH](Cl)Cl
Solvent: ClC(Cl)=C(Cl)Cl
Product: C=CCc1ccc(C(F)(F)F)cc1O[SiH](Cl)Cl

Procedure:
607 g (3 mol) of 2-allyl-5-trifluoromethylphenol as a solution in 600 ml of perchlorethylene was reacted with 1626 g (12 mol) of trichlorosilane to form 2-allyl-5-trifluoromethylphenoxydichlorosilane. BP/1 103 to 105° C.
Reaction SMILES: [C:1]1([CH3:13])[CH:6]=[CH:5][C:4]([N:7]2[CH2:12][CH2:11][NH:10][CH2:9][CH2:8]2)=[CH:3][CH:2]=1.C(N(CC)CC)C.Br.Br.Br[CH2:24][C:25]1[C:26]([NH2:32])=[N:27][C:28]([NH2:31])=[N:29][CH:30]=1>CN(C)C=O>[C:1]1([CH3:13])[CH:2]=[CH:3][C:4]([N:7]2[CH2:8][CH2:9][N:10]([CH2:24][C:25]3[C:26]([NH2:32])=[N:27][C:28]([NH2:31])=[N:29][CH:30]=3)[CH2:11][CH2:12]2)=[CH:5][CH:6]=1
Reactant: Nc1ncc(CBr)c(N)n1
Reactant: Cc1ccc(N2CCNCC2)cc1
Agent: Br
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: Cc1ccc(N2CCN(Cc3cnc(N)nc3N)CC2)cc1
Temperature: 25 °C
Reaction time: 110 h
Yield: 51.1 %

Procedure:
A solution of 0.87 g (0.00493 mol) of 1-p-tolyl-piperazine in 30 ml of dimethylformamide was treated with 1.37 ml (0.00986 mol) of triethylamine and 0.60 g (0.00164 mol) of 5-bromomethyl-pyrimidine-2,4-diamine dihydrobromide and the mixture was stirred at room temperature under argon for 110 hours. The mixture was completely freed from the solvents. The residue was chromatographed over silica gel with methanol as the eluent, digested in dichloromethane/water 1:1 and subsequently filtered off under suction. 0.25 g (51%) of 5-(4-p-tolyl-piperazin-1-ylmethyl)-pyrimidine-2,4-diamine was obtained as beige crystals; m.p. 248°-250°.
Reaction SMILES: [N+:1]([C:4]1[CH:12]=[C:11]2[C:7]([CH2:8][O:9][C:10]2=[O:13])=[CH:6][CH:5]=1)([O-])=O.O.O.Cl[Sn]Cl>Cl.O>[NH2:1][C:4]1[CH:12]=[C:11]2[C:7]([CH2:8][O:9][C:10]2=[O:13])=[CH:6][CH:5]=1
Reactant: O=C1OCc2ccc([N+](=O)[O-])cc21
Agent: Cl
Agent: Cl[Sn]Cl
Solvent: O
Product: Nc1ccc2c(c1)C(=O)OC2
Yield: 83.8 %

Procedure:
To a solution of 6-nitroisobenzofuran-1(3H)-one (15 g, 0.080 mol) in HCl/H2O (375 mL/125 mL) was added SnCl2.2H2O (75 g, 0.33 mol). The reaction mixture was heated at reflux for 4 h before it was quenched with water and extracted with EtOAc (300 mL×3). The organics were dried over Na2SO4 and evaporated in vacuo to give 6-aminoisobenzofuran-1(3H)-one (10 g, 78%). 1H NMR (300 MHz, CDCl3) δ 7.23 (d, J=8.1, 1H), 7.13 (d, J=2.1, 1H), 6.98 (dd, J=8.1, 2.1, 1H), 5.21 (s, 2H), 3.99 (br s, 2H).
Reaction SMILES: [I-:1].[I-].[I-].[CH2:4]([N:7]([C:11]1[CH:12]=[CH:13][C:14]2[C:23]([CH:24]=1)=[S+:22][C:21]1[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=1)[N:15]=2)[CH2:8][CH2:9][CH3:10])[CH2:5][CH3:6].C(N([C:32]1[CH:33]=[CH:34][C:35]2[C:44]([CH:45]=1)=[S+][C:42]1[C:37](=[CH:38][CH:39]=[CH:40][CH:41]=1)[N:36]=2)CCC)CC.C(N(C1C=CC2C(C=1)=[S+]C1C(=CC=CC=1)N=2)CCC)CC.C(NCCCCCC)CCCCC>>[I-:1].[CH2:37]([N:36]([C:19]1[CH:18]=[CH:17][C:16]2[C:21]([CH:20]=1)=[S+:22][C:23]1[C:14](=[CH:13][CH:12]=[C:11]([N:7]([CH2:8][CH2:9][CH3:10])[CH2:4][CH2:5][CH3:6])[CH:24]=1)[N:15]=2)[CH2:35][CH2:34][CH2:33][CH2:32][CH2:45][CH3:44])[CH2:38][CH2:39][CH2:40][CH2:41][CH3:42]
Reactant: CCCN(CCC)c1ccc2nc3ccccc3[s+]c2c1
Agent: CCCCCCNCCCCCC
Agent: [I-]
Product: CCCCCCN(CCCCCC)c1ccc2nc3ccc(N(CCC)CCC)cc3[s+]c2c1

Procedure:
This compound was obtained following isolation of 3-(N,N-dipropylamino)-phenothiazin-5-ium triiodide and subsequent treatment with dihexylamine. Precipitation from dichloromethane by addition of diethyl ether yielded purple lustrous crystals. Mass spectrometry: C30H46N3OS requires m/z=480; found m/z=480 (I− not detected by mass spectrometry).
Reaction SMILES: CC(C)([O-])C.[K+].[OH:7][CH:8]1[CH2:13][CH2:12][O:11][CH2:10][CH2:9]1.F[C:15]1[CH:24]=[C:23]([F:25])[CH:22]=[C:21]2[C:16]=1[C:17](=[O:26])[NH:18][CH:19]=[N:20]2.O>C1COCC1>[F:25][C:23]1[CH:22]=[C:21]2[C:16]([C:17](=[O:26])[NH:18][CH:19]=[N:20]2)=[C:15]([O:7][CH:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)[CH:24]=1
Reactant: O=c1[nH]cnc2cc(F)cc(F)c12
Reactant: OC1CCOCC1
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: O
Solvent: C1CCOC1
Product: O=c1[nH]cnc2cc(F)cc(OC3CCOCC3)c12
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
Potassium tert-butoxide (6.15 g) was added to a solution of 4-hydroxytetrahydropyran (2.94 g) in THF (40 ml) and the mixture was stirred at ambient temperature for 15 minutes. The resultant mixture was added to a stirred solution of 5,7-difluoro-3,4-dihydroquinazolin-4-one (5 g) in THF (60 ml) that was being heated to reflux. A further portion of THF (20 ml) was added and the reaction mixture was heated to reflux for 30 minutes. A second portion of potassium tert-butoxide (6.15 g) was added and the reaction mixture was heated to reflux for 40 minutes. A third portion of potassium tert-butoxide (1.52 g) was added and the reaction mixture was heated to reflux for 20 minutes. The reaction mixture was allowed to cool to ambient temperature. Water (50 ml) was added and the bulk of the organic solvent was evaporated. The residue was acidified to pH<2 by the dropwise addition of 2M aqueous hydrochloric acid. The resultant slurry was stirred for 15 minutes. The mixture was filtered and the isolated solid was washed with water (20 ml) and dried overnight in vacuo at 40° C. There was thus obtained 7-fluoro-5-tetrahydropyran-4-yloxy-3,4-dihydroquinazolin-4-one (5.96 g; 96% HPLC purity using Method A, retention time 3.34 minutes); NMR Spectrum: (DMSOd6) 1.6-1.75 (m, 2H), 1.9-2.0 (m, 2H), 3.5-3.6 (m, 2H), 3.85-3.95 (m, 2H), 4.8 (m, 1H), 6.9 (m, 1H), 7.05 (m, 1H), 8.0 (s, 1H).
Reaction SMILES: [C:1]([Br:5])(Br)(Br)Br.[CH3:6][N:7]1[C:11](CO)=[CH:10][C:9]([CH3:14])=[N:8]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1COCC1>[Br:5][CH2:1][C:11]1[N:7]([CH3:6])[N:8]=[C:9]([CH3:14])[CH:10]=1
Reactant: Cc1cc(CO)n(C)n1
Reactant: BrC(Br)(Br)Br
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: Cc1cc(CBr)n(C)n1
Temperature: 25 °C
Reaction time: 2 h
Yield: 72.9 %

Procedure:
CBr4 (4.7 g, 14.2 mmol) was added to a solution of (1,3-dimethyl-1H-pyrazol-5-yl)methanol (1.2 g, 9.5 mmol) and triphenylphosphine (3.7 g, 14.2 mmol) in THF (20 mL) at 0° C. and the resulting mixture was stirred for approximately 2 h at rt. After concentration in vacuo purification by column chromatography eluting with 2% EtOAc in hexane yielded the title compound (1.31 g, 6.93 mmol).
Reaction SMILES: Br[C:2]1[C:3]([CH3:8])=[N:4][CH:5]=[CH:6][CH:7]=1.[B:9](OC(C)C)([O:14]C(C)C)[O:10]C(C)C.C([Li])CCC.Cl>COCCOC.CCO.O>[CH3:8][C:3]1[C:2]([B:9]([OH:14])[OH:10])=[CH:7][CH:6]=[CH:5][N:4]=1
Reactant: Cc1ncccc1Br
Reactant: CC(C)OB(OC(C)C)OC(C)C
Agent: Cl
Agent: [Li]CCCC
Solvent: O
Solvent: COCCOC
Solvent: CCO
Product: Cc1ncccc1B(O)O
Temperature: -70 °C
Yield: 66.7 %

Procedure:
To a solution of 3-bromo-2-methylpyridine (4.00 g, 23 mmol), triisopropyl borate (6.40 mL, 28 mmol) in 50 mL of 4/1 toluene/THF (4/1, 50 mL) at −78° C. was added was added butyllithium (17 mL, 28 mmol), dropwise. The mixture was allowed to warm up to 30 min at −70° C. LCMS and then to 20° C. HCl (2M) was added to bring the solution to pH1. Then water (20 mL) was added and the mixture was extracted with toluene. The aqueous layer was neutralized with 1 M NaOH and extracted with dichloromethane. The aqueous layer was concentrated to dryness and the white solid was washed with dichloromethane. The combined organic layers were dried over sodium sulfate, filtered and concentrated to give 2.10 g of 2-methylpyridin-3-ylboronic acid as a yellow oil.
Reaction SMILES: [CH:1]1([N:5]2[CH2:10][CH2:9][N:8]([C:11]([C:13]3[CH:14]=[C:15]4[C:19](=[CH:20][CH:21]=3)[NH:18][C:17]([C:22]([N:24]3[CH2:29][CH2:28][S:27](=[O:31])(=[O:30])[CH2:26][CH2:25]3)=[O:23])=[CH:16]4)=[O:12])[CH2:7][CH2:6]2)[CH2:4][CH2:3][CH2:2]1.[H-].[Na+].Br[CH:35]([CH3:37])[CH3:36]>CN(C)C=O>[CH:1]1([N:5]2[CH2:6][CH2:7][N:8]([C:11]([C:13]3[CH:14]=[C:15]4[C:19](=[CH:20][CH:21]=3)[N:18]([CH:35]([CH3:37])[CH3:36])[C:17]([C:22]([N:24]3[CH2:29][CH2:28][S:27](=[O:30])(=[O:31])[CH2:26][CH2:25]3)=[O:23])=[CH:16]4)=[O:12])[CH2:9][CH2:10]2)[CH2:2][CH2:3][CH2:4]1
Reactant: CC(C)Br
Reactant: O=C(c1ccc2[nH]c(C(=O)N3CCS(=O)(=O)CC3)cc2c1)N1CCN(C2CCC2)CC1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CC(C)n1c(C(=O)N2CCS(=O)(=O)CC2)cc2cc(C(=O)N3CCN(C4CCC4)CC3)ccc21
Yield: 49 %

Procedure:
The title compound was synthesized in analogy to example 51, from [5-(4-cyclobutyl-piperazine-1-carbonyl)-1H-indol-2-yl]-(1,1-dioxothiomorpholin-4-yl)-methanone (example 202), sodium hydride and 2-bromopropane in N,N-dimethylformamide, to give the desired product as a light brown foam (49%).
Reaction SMILES: CS(C)=O.CC(C)([O-])C.[K+].[NH2:11][C:12]1[CH:13]=[N:14][CH:15]=[N:16][CH:17]=1.Br[C:19]1[CH:24]=[CH:23][C:22]([N+:25]([O-:27])=[O:26])=[CH:21][N:20]=1>O>[N+:25]([C:22]1[CH:23]=[CH:24][C:19]([NH:11][C:12]2[CH:13]=[N:14][CH:15]=[N:16][CH:17]=2)=[N:20][CH:21]=1)([O-:27])=[O:26]
Reactant: O=[N+]([O-])c1ccc(Br)nc1
Reactant: Nc1cncnc1
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: CS(C)=O
Solvent: O
Product: O=[N+]([O-])c1ccc(Nc2cncnc2)nc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 59.8 %

Procedure:
To 7 ml of dimethyl sulfoxide was added 0.69 g (6.15 mmol) of potassium tert-butoxide, and 468 mg (4.92 mmol) of 5-aminopyrimidine was added to the solution while cooling with water. After stirring at room temperature for 1 hour, 500 mg (2.46 mmol) of 2-bromo-5-nitropyridine was added thereto under cooling with water, followed by further stirring at room temperature for 30 minutes. The reaction solution was poured into ice-water and extracted with ethyl acetate. The organic layer was washed with 1 N hydrochloric acid, and the washing was adjusted to pH 8.5 with a 1 N sodium hydroxide aqueous solution and again extracted with ethyl acetate. The organic layer was combined with the above obtained organic layer, washed successively with water and a saturated sodium chloride aqueous solution, and dried over magnesium sulfate. The solvent was removed by distillation under reduced pressure, and the residue was purified by silica gel column chromatography (eluting solvent: chloroform-methanol). The resulting crude crystals were washed with ethyl ether to obtain 0.32 g (1.47 mmol) of 5-[N-(5-nitro-2-pyridyl)amino]pyrimidine.
Reaction SMILES: CCN(C(C)C)C(C)C.I[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH3:26].[CH3:27][C@@H:28]([C:31]([N:33]1[C@H:37]([C:38]([OH:40])=[O:39])[CH2:36][CH2:35][CH2:34]1)=[O:32])[CH2:29][SH:30].C1CCN2C(=NCCC2)CC1>O1CCCC1>[CH2:11]([S:30][CH2:29][C@@H:28]([CH3:27])[C:31]([N:33]1[CH2:34][CH2:35][CH2:36][C@H:37]1[C:38]([OH:40])=[O:39])=[O:32])[CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH3:26]
Reactant: C[C@H](CS)C(=O)N1CCC[C@H]1C(=O)O
Reactant: CCCCCCCCCCCCCCCCI
Solvent: C1CCOC1
Solvent: C1CCC2=NCCCN2CC1
Solvent: CCN(C(C)C)C(C)C
Product: CCCCCCCCCCCCCCCCSC[C@@H](C)C(=O)N1CCC[C@H]1C(=O)O
Temperature: 70 °C
Yield: 47.5 %

Procedure:
DIEA (188 μl, 1.10 mmol) was added to a solution of 1-iodohexadecane (176 mg, 0.500 mmol), captopril (120 mg, 0.550 mmol) and DBU (165 μl, 1.10 mmol) in tetrahydrofuran (5 ml). The mixture was heated at 70° C. for 2 h and then concentrated. The residue was poured onto water saturated with potassium hydrogensulphate and organic material was extracted into chloroform. The organic phase was washed with water and dried (MgSO4). The product purified by chromatography (silica, CHCl3/MeOH/AcOH 85:10:5) and lyophilised to give 105 mg (48%) of white solid material. The structure was verified by 1H (500 MHz) and 13C (125 MHz) analysis and further characterised by MALDI mass spectrometry, giving M−H in negative mode at m/z 440 as expected.
Reaction SMILES: [CH3:1][NH:2][C:3](=[O:18])[CH:4]=[C:5]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[C:7]2([CH2:17][CH2:16][CH2:15][CH2:14]2)[CH2:6]1.C(=O)(O)[O-:20].[Na+].ClC1C=CC=C(C(OO)=O)C=1>ClCCl>[OH:20][CH:4]([C:5]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[C:7]2([CH2:14][CH2:15][CH2:16][CH2:17]2)[CH:6]=1)[C:3]([NH:2][CH3:1])=[O:18]
Reactant: CNC(=O)C=C1CC2(CCCC2)c2ccccc21
Reactant: O=C([O-])O
Agent: O=C(OO)c1cccc(Cl)c1
Agent: [Na+]
Solvent: ClCCl
Product: CNC(=O)C(O)C1=CC2(CCCC2)c2ccccc21
Temperature: 20 °C
Reaction time: 1.5 h

Procedure:
N-Methyl-[spiro(cyclopentane-1,1'-indan)-3'-yliden]acetamide (9.6 g; Swedish Pat. No. 7203905-0) is dissolved in dichloromethane (200 ml) and added to sodium bicarbonate solution (30 ml; 0.5 M). The solution is treated with m-chloroperbenzoic acid (13.76 g of a 50% product) in small portions with stirring at about 20° C. After stirring for an additional 2 hours, the solution is washed with saturated sodium carbonate solution and water and dried with sodium sulphate. The solvent is evaporated and the remaining oil is dissolved in tetrahydrofuran (100 ml). Perchloric acid (70%, 10 drops) is added and the mixture is kept at about 20° C. for 1.5 hour. Evaporation of the solvent in vacuo gives the crude α-hydroxy-N-methyl-[spiro(cyclopentane-1,1'-indene)-3'-yl]acetamide as a viscous oil. A sample is triturated with diisopropyl ether and the crystalline product obtained is recrystallized from this solvent. A colourless product is obtained, melting at 136°-138° C. The crude hydroxyamide is dissolved in anhydrous diethyl ether (200 ml) and added dropwise to a suspension of lithium aluminium hydride (30 g) in anhydrous ether (500 ml). The mixture is stirred at room temperature for 5 days and the excess of hydride is destroyed with ethyl acetate, followed by saturated aqueous sodium sulphate solution. The ether phase is washed with water and dried. Evaporation of the solvent gives the crude title compound, which after crystallization from diisopropyl ether melts at 134° C.