Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH:1][C@@:2]1([CH2:20][OH:21])[CH2:11][C:10]2[C:5](=[C:6]([O:14][CH3:15])[CH:7]=[CH:8][C:9]=2[O:12][CH3:13])[C:4]2([S:19][CH2:18][CH2:17][S:16]2)[CH2:3]1.[C:22](OC(=O)C)(=[O:24])[CH3:23]>N1C=CC=CC=1>[C:22]([O:21][CH2:20][C@:2]1([OH:1])[CH2:11][C:10]2[C:5](=[C:6]([O:14][CH3:15])[CH:7]=[CH:8][C:9]=2[O:12][CH3:13])[C:4]2([S:16][CH2:17][CH2:18][S:19]2)[CH2:3]1)(=[O:24])[CH3:23]
Reactant: COc1ccc(OC)c2c1C[C@@](O)(CO)CC21SCCS1
Reactant: CC(=O)OC(C)=O
Solvent: c1ccncc1
Product: COc1ccc(OC)c2c1C[C@@](O)(COC(C)=O)CC21SCCS1
Temperature: 0 °C
Reaction time: 20 h

Procedure:
1.6 g of (S)-1',2',3',4'-tetrahydro-3'-hydoxy-3'-hydroxymethyl-5',8'-dimethoxyspiro[1,3-dithiolane-2,1'-naphthalene] were dissolved in 30 ml of dry pyridine and 1.5 g of acetic anhydride were added to the solution. The mixture was left to stand at room temperature for 20 hours and then poured into ice-cold 5-M sulphuric acid. The resulting mixture was extracted with ethyl acetate, the extracts were washed with water and sodium hydrogen carbonate solution, dried and evaporated to give (S)-3'-acetoxymethyl-1',2',3',4'-tetrahydro-3'-hydroxy-5',8'-dimethoxyspiro[1,3-dithiolane-2,1'-naphthalene] in the form of a colourless oil which was used directly in the next step.
Reaction SMILES: [CH:1]1([C:4]([OH:6])=O)[CH2:3][CH2:2]1.CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.C(N(CC)CC)C.[NH2:36][C:37]1[C:45]2[C:40](=[CH:41][CH:42]=[C:43]([C:46]3[O:50][C:49]([NH:51][CH:52]([CH3:54])[CH3:53])=[N:48][N:47]=3)[CH:44]=2)[NH:39][CH:38]=1>CN(C=O)C>[CH:52]([NH:51][C:49]1[O:50][C:46]([C:43]2[CH:44]=[C:45]3[C:40](=[CH:41][CH:42]=2)[NH:39][CH:38]=[C:37]3[NH:36][C:4]([CH:1]2[CH2:3][CH2:2]2)=[O:6])=[N:47][N:48]=1)([CH3:54])[CH3:53]
Reactant: CC(C)Nc1nnc(-c2ccc3[nH]cc(N)c3c2)o1
Reactant: O=C(O)C1CC1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: CC(C)Nc1nnc(-c2ccc3[nH]cc(NC(=O)C4CC4)c3c2)o1
Reaction time: 0.25 h
Yield: 11.1 %

Procedure:
To a solution of cyclopropanecarboxylic acid (55 mg, 0.642 mmol) in DMF (6 mL) was added EDC.HCl (167 mg, 0.875 mmol), HOBt (118 mg, 0.875 mmol) and triethylamine (0.244 mL, 1.75 mmol). The mixture was stirred for 15 min, then 5-(3-amino-1H-indol-5-yl)-N-isopropyl-1,3,4-oxadiazol-2-amine (150 mg, 0.583 mmol) was added and the mixture was stirred for 16 h at RT. The reaction was quenched with water and extracted with EtOAc. The organic layer was dried over anhydrous Na2SO4, filtered and concentrated. The residue was purified with basic alumina chromatography to give N-(5-(5-(isopropylamino)-1,3,4-oxadiazol-2-yl)-1H-indol-3-yl)cyclopropane carboxamide (21 mg, 11%). MS (ESI, pos. ion) m/z: 326.2 (M+1); 1H-NMR (300 MHz, DMSO-d6): δ 11.13 (s, 1H), 10.43 (s, 1H), 8.37 (brs, 1H), 7.75 (d, 1H, J=2.1 Hz), 7.41-7.55 (m, 3H), 3.70-3.76 (m, 1H), 1.92-1.97 (m, 1H), 1.21 (d, 6H, J=6.6 Hz), 0.77-0.79 (m, 4H).
Reaction SMILES: [CH3:1][CH:2]1[S:7][C:6](=[O:8])[NH:5][N:4]=[C:3]1[C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][C:13](=[O:18])[C:12]2=[N:19]C1C=CC=CC=1.Cl.Cl.[CH2:28]([NH:35]N)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1>>[C:29]1([CH2:28][NH:35][N:19]=[C:12]2[C:11]3[C:15](=[CH:16][CH:17]=[C:9]([C:3]4[CH:2]([CH3:1])[S:7][C:6](=[O:8])[NH:5][N:4]=4)[CH:10]=3)[NH:14][C:13]2=[O:18])[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1
Reactant: CC1SC(=O)NN=C1c1ccc2c(c1)C(=Nc1ccccc1)C(=O)N2
Reactant: NNCc1ccccc1
Agent: Cl
Product: CC1SC(=O)NN=C1c1ccc2c(c1)C(=NNCc1ccccc1)C(=O)N2
Yield: 24 %

Procedure:
Starting from 1,3-dihydro-5-(3,6-dihydro-6-methyl-2-oxo -2H-1,3,4-thiadiazin-5-yl)-3-phenylimino-2H-indol-2-one, and benzylhydrazine dihydrochloride and following the method described in Example 21, the desired compound was obtained.
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][CH2:2]1.[C:10]([O:14][C:15](=O)[O:16]C(C)(C)C)([CH3:13])([CH3:12])[CH3:11]>O1CCCC1>[N:1]1([C:15]([O:14][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:16])[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][CH2:2]1
Reactant: c1ccc2c(c1)CCN2
Reactant: CC(C)(C)OC(=O)OC(C)(C)C
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N1CCc2ccccc21
Temperature: 25 °C
Reaction time: 16 h
Yield: 82 %

Procedure:
Indoline (10 g, 84 mmol) was dissolved in tetrahydrofuran (100 mL) and di-tert-butylcarbonate (22 g, 0.1 mol) was added. The mixture was left stirring for 16 hours at room temperature under an inert nitrogen atmosphere. The tetrahydrofuran was removed in vacuo and the crude product purified by vacuum distillation to give the title compound (15.1 g) as a clear pale pink oil that crystallised upon standing (temperature: 160-162° C., pressure 1-0.1 mm Hg).
Reaction SMILES: [SH:1][C:2]1[NH:3][C:4]2[CH:9]=[CH:8][N:7]=[CH:6][C:5]=2[N:10]=1.[Na].[C:12]([O:20][C:21]1[CH:26]=[CH:25][C:24]([CH2:27]Br)=[CH:23][CH:22]=1)(=[O:19])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1>>[C:12]([O:20][C:21]1[CH:22]=[CH:23][C:24]([CH2:27][S:1][C:2]2[NH:3][C:4]3[CH:9]=[CH:8][N:7]=[CH:6][C:5]=3[N:10]=2)=[CH:25][CH:26]=1)(=[O:19])[C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1
Reactant: Sc1nc2cnccc2[nH]1
Reactant: O=C(Oc1ccc(CBr)cc1)c1ccccc1
Agent: [Na]
Product: O=C(Oc1ccc(CSc2nc3cnccc3[nH]2)cc1)c1ccccc1
Yield: 53.4 %

Procedure:
The synthesis of this compound proceeded in the same fashion as in Example 15 using 4.17 g (0.028 mol) of 2-mercapto-1H-imidazo[4,5-c]pyridine, 0.70 g (0.030 g atom) of sodium, and 8.04 g (0.028 mol) of 4-(bromomethyl)phenyl benzoate. The filtered precipitate (7.90 g) was recrystallized from methylene chloride to give 5.40 g of product, m.p. 171°-174° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:20]=[CH:19][C:6]([CH2:7][C:8]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[C:11](Cl)=[N:10][N:9]=2)=[CH:5][CH:4]=1.[C:21]1(B(O)O)[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.O1CCOCC1.C(=O)([O-])[O-].[Na+].[Na+]>CCOC(C)=O>[CH3:1][O:2][C:3]1[CH:20]=[CH:19][C:6]([CH2:7][C:8]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[C:11]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)=[N:10][N:9]=2)=[CH:5][CH:4]=1
Reactant: COc1ccc(Cc2nnc(Cl)c3ccccc23)cc1
Reactant: OB(O)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: C1COCCO1
Solvent: CCOC(C)=O
Product: COc1ccc(Cc2nnc(-c3ccccc3)c3ccccc23)cc1
Temperature: 100 °C

Procedure:
To 1,1′-bis(diphenylphosphoino)ferrocene-palladium dichloride (0.046 g, 0.063 mmol), 1-(4 -methoxybenzyl)-4-chlorophthalazine (0.360 g, 1.3 mmol), and phenylboronic acid (0.39 g, 3.2 mmol) was added dioxane (4.0 mL) and sodium carbonate (2.0M, aq)(1.9 ml, 3.8 mmol). The resulting mixture was heated to 100° C. in a sealed tube for 1 hour. The reaction was diluted with EtOAc and extracted with water and brine. The organic layers were dried over sodium sulfate, filtered, concentrated, and the crude was purified by ISCO silica gel chromatography (10-100% EtOAc/hexanes, 40 g column). Concentrated the product fractions to yield 1-(4-methoxybenzyl)-4-phenylphthalazine as a light yellow solid. MS m/z=327 [M+1]+. Calc'd for C22H18N2O: 326.40.
Reaction SMILES: [CH:1]1([CH:7]=[O:8])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[Zn](CC)CC.[C:14]1(C)[CH:19]=CC=C[CH:15]=1>>[CH3:19][C:14]([C@H:7]([CH:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1)[OH:8])=[CH2:15]
Reactant: Cc1ccccc1
Reactant: O=CC1CCCCC1
Agent: CC[Zn]CC
Product: C=C(C)[C@@H](O)C1CCCCC1
Temperature: 0 °C
Yield: 90 %

Procedure:
Into a 20-mL scintal vial 46.5 mg (0.41 mmol) cyclohexanecarboxaldehyde was added dropwise (neat) and diluted with 1.5 mL toluene in a nitrogen atmosphere glovebox. A dry and thoroughly purged (N2) 10 mL Schlenk flask capped with a rubber septum was charged with 4.0 mg (0.017 mmol) (−)-MIB and a stir bar. In the glovebox, 65.5 mg (0.44 mmol) 3 was weighed into the Schlenk flask and the solids diluted with toluene (2 mL). 3.1 eq. (125 μL, 1.23 mmol) Et2Zn was then added neat. The flask was cooled to 0° C. and the aldehyde was added dropwise under an N2 purge. The reaction was stirred until judged complete by TLC and then quenched with saturated NH4Cl (6 mL). The clear biphasic layers were partitioned and the aqueous layer was repeatedly extracted with diethyl ether (3×25 mL). The combined organic layer was washed with brine, dried over MgSO4 and concentrated. The crude product was purified by column chromatography on silica (70:20:10, hexanes:CH2Cl2:EtOAc) to afford the title compound as a colorless oil in 90% yield (58 mg, 0.37 mmol). [α]D20=−16.7 (c=0.104, CHCl3, 92% ee). 1H NMR (C6D6, 500 MHz): δ.0.88-0.98 (m, 2H; methylene), 1.09-1.17 (m, 3H; methylene), 1.18 (br, 1H; OH), 1.35 (m, 1H; methylene), 1.46 (m, 1H; methylene), 1.58 (m, 1H; methylene), 1.59 (s, 3H; CH3), 1.64 (m, 1H; methylene), 1.71 (m, 1H; methylene), 2.01 (m, 1H; methylene), 3.54 (d, 4 Hz, 1H; RCHOH), 4.78 (s, 1H; alkene), 4.84 (s, 1H; alkene) ppm. 13C{1H} NMR (C6D6, 125 MHz): δ.17.88, 26.81, 26.98, 27.25, 29.02, 30.39, 41.25, 81.16, 112.26, 147.48 ppm. IR (neat): 3383 (OH), 2919, 2848, 1648, 1446, 1372, 1260, 1080, 1019 cm−1. LRMS-CI m/z 136.13 [(M−□□□)+; calcd for; C10H17: 136.13].
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4](B(O)O)[CH:5]=[CH:6][C:7]=1[C@H:8]([NH:10][C:11]([C:13]1([NH:16][C:17](=[O:22])[C:18]([F:21])([F:20])[F:19])[CH2:15][CH2:14]1)=[O:12])[CH3:9].P([O-])([O-])([O-])=O.[K+].[K+].[K+].[F:34][C:35]([F:56])([F:55])[S:36]([O:39][C:40]1[C:45](OS(C(F)(F)F)(=O)=O)=[CH:44][CH:43]=[CH:42][C:41]=1[Cl:54])(=[O:38])=[O:37]>O1CCOCC1.CO.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:56][C:35]([F:34])([F:55])[S:36]([O:39][C:40]1[C:41]([Cl:54])=[CH:42][CH:43]=[CH:44][C:45]=1[C:4]1[CH:5]=[CH:6][C:7]([C@H:8]([NH:10][C:11]([C:13]2([NH:16][C:17](=[O:22])[C:18]([F:21])([F:20])[F:19])[CH2:15][CH2:14]2)=[O:12])[CH3:9])=[C:2]([F:1])[CH:3]=1)(=[O:38])=[O:37]
Reactant: O=S(=O)(Oc1cccc(Cl)c1OS(=O)(=O)C(F)(F)F)C(F)(F)F
Reactant: C[C@@H](NC(=O)C1(NC(=O)C(F)(F)F)CC1)c1ccc(B(O)O)cc1F
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=P([O-])([O-])[O-]
Agent: [K+]
Solvent: C1COCCO1
Solvent: CO
Product: C[C@@H](NC(=O)C1(NC(=O)C(F)(F)F)CC1)c1ccc(-c2cccc(Cl)c2OS(=O)(=O)C(F)(F)F)cc1F
Temperature: 90 °C

Procedure:
3-Fluoro-4-{(1R)-1-[({1-[(trifluoroacetyl)amino]cyclopropyl}carbonyl)amino]ethyl}-phenylboronic acid (0.050 g, 0.138 mmol), tetrakis(triphenylphosphine)palladium (0) (0.016 g, 0.014 mmol), and potassium phosphate (0.035 g, 0.166 mmol) were added to a flame-dried flask under argon. 2-Chloro-6-{[(trifluoromethyl)sulfonyl]oxy}phenyl trifluoromethanesulfonate (0.068 g, 1.66 mmol) as a solution in dioxane (0.33M) was added to the solids and heated to 90° C. After 3 hours the reaction was diluted with methanol, filtered and purified by reverse phase chromatography using a gradient from 95/5H2O/CH3CN to 5/95H2O/CH3CN. The product was lyophilized to yield the title compound as a solid.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[C:7]([O:9][CH3:10])[CH:6]=[CH:5][C:4]=1[CH2:11][N:12]([CH:38]1[CH2:40][CH:39]1[C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)[C:13]1[C:14]2[N:25]=[N:24][N:23]([CH:26]3[CH:30]4[O:31]C(C)(C)[O:33][CH:29]4[CH:28]([CH2:36][OH:37])[CH2:27]3)[C:15]=2[N:16]=[C:17]([S:19][CH2:20][CH2:21][CH3:22])[N:18]=1.CO.C(OCC)(=O)C>FC(F)(F)C(O)=O>[CH3:1][O:2][C:3]1[CH:8]=[C:7]([O:9][CH3:10])[CH:6]=[CH:5][C:4]=1[CH2:11][N:12]([CH:38]1[CH2:40][CH:39]1[C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)[C:13]1[C:14]2[N:25]=[N:24][N:23]([CH:26]3[CH2:27][CH:28]([CH2:36][OH:37])[CH:29]([OH:33])[CH:30]3[OH:31])[C:15]=2[N:16]=[C:17]([S:19][CH2:20][CH2:21][CH3:22])[N:18]=1
Reactant: CCCSc1nc(N(Cc2ccc(OC)cc2OC)C2CC2c2ccccc2)c2nnn(C3CC(CO)C4OC(C)(C)OC43)c2n1
Solvent: CCOC(C)=O
Solvent: O=C(O)C(F)(F)F
Solvent: CO
Product: CCCSc1nc(N(Cc2ccc(OC)cc2OC)C2CC2c2ccccc2)c2nnn(C3CC(CO)C(O)C3O)c2n1
Yield: 85.1 %

Procedure:
A solution of the product from Example 36, step (a) (1.39 g) in trifluoroacetic acid (1.5 ml)/methanol (15 ml) was stirred for two days. Ethyl acetate was added and the mixture was concentrated. Sodium hydrogen carbonate solution was added and the mixture was extracted with ethyl acetate. The organic extracts were dried, concentrated and purified (SiO2, petrol:acetone 1:1 as eluant) to give the subtitle compound (1.11 g).
Reaction SMILES: [CH3:1][O:2][CH2:3][CH2:4][N:5]1[C:9]([CH3:10])=[C:8]([CH3:11])[S:7][C:6]1=[NH:12].CCN(CC)CC.[Cl:20][C:21]1[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][C:22]=1[C:23](Cl)=[O:24]>C1COCC1>[Cl:20][C:21]1[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][C:22]=1[C:23](/[N:12]=[C:6]1\[S:7][C:8]([CH3:11])=[C:9]([CH3:10])[N:5]\1[CH2:4][CH2:3][O:2][CH3:1])=[O:24]
Reactant: O=C(Cl)c1cc(Cl)ccc1Cl
Reactant: COCCn1c(C)c(C)sc1=N
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: COCCn1c(C)c(C)s/c1=N\C(=O)c1cc(Cl)ccc1Cl
Yield: 26 %

Procedure:
The product of Example 126A (0.20 g, 1.1 mmol), Et3N (0.45 mL, 3.2 mmol) and 2,5-dichlorobenzoyl chloride in 15 mL THF were processed using the method described in Example 132 to afford the title compound (0.10 g, 0.28 mmol, 26% yield). 1H NMR (300 MHz, CDCl3) δ ppm 2.25 (d, J=1.0 Hz, 3H), 2.28 (d, J=1.0 Hz, 3H), 3.31 (s, 3H), 3.76 (t, J=5.3 Hz, 2H), 4.36 (t, J=5.3 Hz, 2H), 7.28 (d, J=2.4 Hz, 1H), 7.32-7.36 (m, 1H), 7.94 (d, J=2.4 Hz, 1H); MS (DCI/NH3) m/z 359 (M+H)+; Anal. calculated for C15H16Cl2N2O2S: C, 50.15; H, 4.49; N, 7.80. Found: C, 50.22; H, 4.15; N, 7.63.
Reaction SMILES: C([NH:9][C:10]1[N:18]=[CH:17][N:16]=[C:15]2[C:11]=1[N:12]=[CH:13][N:14]2[CH:19]1[CH:23]([O:24]C(=O)C)[CH:22]([O:28][CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[C:21]([C:38]([C:51]2[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=2)([C:45]2[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=2)[O:39][SiH2:40][C:41]([CH3:44])([CH3:43])[CH3:42])([CH:36]=[CH2:37])[O:20]1)(=O)C1C=CC=CC=1.N>CO>[NH2:9][C:10]1[N:18]=[CH:17][N:16]=[C:15]2[C:11]=1[N:12]=[CH:13][N:14]2[CH:19]1[CH:23]([OH:24])[CH:22]([O:28][CH2:29][C:30]2[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=2)[C:21]([C:38]([C:51]2[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=2)([C:45]2[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=2)[O:39][SiH2:40][C:41]([CH3:42])([CH3:43])[CH3:44])([CH:36]=[CH2:37])[O:20]1
Reactant: C=CC1(C(O[SiH2]C(C)(C)C)(c2ccccc2)c2ccccc2)OC(n2cnc3c(NC(=O)c4ccccc4)ncnc32)C(OC(C)=O)C1OCc1ccccc1
Agent: N
Solvent: CO
Product: C=CC1(C(O[SiH2]C(C)(C)C)(c2ccccc2)c2ccccc2)OC(n2cnc3c(N)ncnc32)C(O)C1OCc1ccccc1
Yield: 96 %

Procedure:
To a flask charged with Acetic acid 2-(6-benzoylamino-purin-9-yl)-4-benzyloxy-5-(tert-butyl-diphenyl-silanyloxymethyl)-5-vinyl-tetrahydro-furan-3-yl ester was added methanol and NH3. The reaction was stirred, extracted, and the solvent was evaporated to provide the titled compound in 96% yield.
Reaction SMILES: [Br:1][C:2]([CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][Si:10]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)([CH3:12])[CH3:11])=[CH2:3].[OH-].[K+].[Br-].[Br-].C([N+](CC)(CC)CC[N+](CC1C=CC=CC=1)(CC)CC)C1C=CC=CC=1.[CH:49]([Br:52])(Br)[Br:50]>C(Cl)Cl.O>[C:13]1([Si:10]([CH3:12])([CH3:11])[CH2:9][CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][C:2]2([Br:1])[CH2:3][C:49]2([Br:52])[Br:50])[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: BrC(Br)Br
Reactant: C=C(Br)CCCCCC[Si](C)(C)c1ccccc1
Agent: CC[N+](CC)(CC[N+](CC)(CC)Cc1ccccc1)Cc1ccccc1
Agent: [Br-]
Agent: [K+]
Solvent: ClCCl
Solvent: O
Product: C[Si](C)(CCCCCCC1(Br)CC1(Br)Br)c1ccccc1
Reaction time: 8 h
Yield: 47.7 %

Procedure:
A mixture of 1.4 g (4.3 mmol) of 2-bromo-8-(phenyldimethylsilyl)-oct-1-ene, 3.2 g of 45% aqueous potassium hydroxide solution (25.6 mmol), 0.2 g N,N′-dibenzyl-N,N,N′,N′-tetraethylethylenediammonium dibromide, and 7.5 ml of methylene chloride was treated with 1.1 ml of bromoform (12.6 mmol). The well-stirred reaction mixture was held overnight at room temperature. Water and methylene chloride were added, the phases were separated. The methylene chloride phase was dried over magnesium sulfate, and stripped. A small amount of heptane was added during the strip to help remove remaining bromoform. Column chromatography gave 1.02 g of 2-(6-(phenyldimethylsilyl)-hexyl)-1,1,2-tribromocyclopropane as a colorless liquid.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:11]=[C:10]2[C:6]([CH:7]=[C:8]([C:12](OC)=[O:13])[NH:9]2)=[CH:5][C:4]=1[CH3:16].[NH3:17]>CO>[CH3:1][O:2][C:3]1[CH:11]=[C:10]2[C:6]([CH:7]=[C:8]([C:12]([NH2:17])=[O:13])[NH:9]2)=[CH:5][C:4]=1[CH3:16]
Reactant: N
Reactant: COC(=O)c1cc2cc(C)c(OC)cc2[nH]1
Solvent: CO
Product: COc1cc2[nH]c(C(N)=O)cc2cc1C

Procedure:
200 mg of methyl 6-methoxy-5-methyl-1H-indole-2-carboxylate (1 mmol) was heated at 80 degrees in a sealed tube with 2 mL of 7M ammonia in methanol. After one week reaction the solvent evaporated to produce 202 mg of 6-methoxy-5-methyl-1H-indole-2-carboxamide that was used without purification in the next step.
Reaction SMILES: I[C:2]1[CH:7]=[CH:6][C:5]2[C:8]3[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH:10]([CH3:21])[C:9]=3[O:22][C:4]=2[CH:3]=1.[I:23]C1C=CC2OC3C(C)NCCC=3C=2C=1>>[I:23][C:7]1[CH:2]=[CH:3][C:4]2[O:22][C:9]3[CH:10]([CH3:21])[N:11]([C:14]([O:16][C:17]([CH3:19])([CH3:20])[CH3:18])=[O:15])[CH2:12][CH2:13][C:8]=3[C:5]=2[CH:6]=1
Reactant: CC1NCCc2c1oc1ccc(I)cc21
Reactant: CC1c2oc3cc(I)ccc3c2CCN1C(=O)OC(C)(C)C
Product: CC1c2oc3ccc(I)cc3c2CCN1C(=O)OC(C)(C)C

Procedure:
Synthesized as described for tert-butyl 7-iodo-1-methyl-3,4-dihydro[1]benzofuro[2,3-c]pyridine-2(1H)-carboxylate starting from 6-iodo-1-methyl-1,2,3,4-tetrahydro[1]benzofuro[2,3-c]pyridine. MS m/z 414 [M+H]+. 1H-NMR (400 MHz, CDCl3): δ 1.47 (d, J=6.8 Hz, 3H), 1.51 (s, 9H), 2.57 (m, 1H), 2.71 (m, 1H), 3.05 (m, 1H), 4.38 (m, 1H), 5.21 (m, 1H), 7.20 (d, J=8.6 Hz, 1H), 7.51 (dd, J=8.6, 1.8 Hz, 1H), 7.76 (s, 1H).
Reaction SMILES: Cl.[Cl:2][C:3]1[CH:4]=[C:5]([NH:18][C:19]2[C:20]3[NH:27][CH:26]=[CH:25][C:21]=3[N:22]=[CH:23][N:24]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([F:17])[CH:12]=1.C(=O)([O-])[O-].[K+].[K+].[CH3:34][O:35][C:36]1[CH:37]=[C:38]([S:44](Cl)(=[O:46])=[O:45])[CH:39]=[CH:40][C:41]=1[O:42][CH3:43]>CN(C)C=O.C(OCC)(=O)C>[Cl:2][C:3]1[CH:4]=[C:5]([NH:18][C:19]2[C:20]3[N:27]([S:44]([C:38]4[CH:39]=[CH:40][C:41]([O:42][CH3:43])=[C:36]([O:35][CH3:34])[CH:37]=4)(=[O:46])=[O:45])[CH:26]=[CH:25][C:21]=3[N:22]=[CH:23][N:24]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([F:17])[CH:12]=1
Reactant: Fc1cccc(COc2ccc(Nc3ncnc4cc[nH]c34)cc2Cl)c1
Reactant: COc1ccc(S(=O)(=O)Cl)cc1OC
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: COc1ccc(S(=O)(=O)n2ccc3ncnc(Nc4ccc(OCc5cccc(F)c5)c(Cl)c4)c32)cc1OC
Reaction time: 1 h
Yield: 45.1 %

Procedure:
N-{3-Chloro-4-[(3-fluorobenzyl)oxy]phenyl}-5H-pyrrolo[3,2-d]pyrimidin-4-amine hydrochloride (150 mg) was dissolved in N,N-dimethylformamide (1.5 mL), and potassium carbonate (102 mg) and (3,4-dimethoxyphenyl)sulfonyl chloride (96.9 mg) were sequentially added under ice-cooling. The mixture was stirred under ice-cooling for 2 hrs, and at room temperature for 1 hr. The mixture was diluted with ethyl acetate (50 mL) and washed twice with water (30 mL). The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The residue was separated and purified by silica gel column chromatography (eluent, hexane:ethyl acetate=80:20→0:100) to give the title compound (95 mg) as a powder.
Reaction SMILES: [C:1]([O:6][CH2:7][CH:8]1[O:10][CH2:9]1)(=[O:5])[C:2]([CH3:4])=[CH2:3].[C:11]([NH2:15])([CH3:14])([CH3:13])[CH3:12]>C(O)(C)C>[C:1]([O:6][CH2:7][CH:8]([OH:10])[CH2:9][NH:15][C:11]([CH3:14])([CH3:13])[CH3:12])(=[O:5])[C:2]([CH3:4])=[CH2:3]
Reactant: C=C(C)C(=O)OCC1CO1
Reactant: CC(C)(C)N
Solvent: CC(C)O
Product: C=C(C)C(=O)OCC(O)CNC(C)(C)C
Reaction time: 3.5 h

Procedure:
There were charged to a glass pressure reactor having a volume of 250 ml, 30 ml of isopropyl alcohol, 20 grams of 90 percent pure glycidyl methacrylate and 9.92 grams of t-butylamine. The reactor was then placed in a water bath at 60° C. for 3.5 hours. Thereafter the solution was cooled in an ice bath, and a white, crystalline precipitate formed, which weighed 17.7 grams after drying. The filtrate was partially concentrated and a second filtration gave an additional 1.3 grams of the same white, crystalline solid product. This yield equalled about 70 percent based on the amount of glycidyl methacrylate charged. The melting point of this solid product was 66°-67° C. The structure of the 2-hydroxy-3-t-butylamino-1-propyl methacrylate produced was further confirmed by nuclear magnetic resonance, infrared analysis and mass spectroscopy.
Reaction SMILES: C[O:2][C:3]([C:5]1[CH:6]=[C:7]([Br:14])[C:8]2[O:12][CH:11]=[CH:10][C:9]=2[CH:13]=1)=O.[H-].C([Al+]CC(C)C)C(C)C.[F-].[Na+].O>ClCCl>[OH:2][CH2:3][C:5]1[CH:6]=[C:7]([Br:14])[C:8]2[O:12][CH:11]=[CH:10][C:9]=2[CH:13]=1
Reactant: COC(=O)c1cc(Br)c2occc2c1
Agent: CC(C)C[Al+]CC(C)C
Agent: [F-]
Agent: [H-]
Solvent: O
Solvent: ClCCl
Product: OCc1cc(Br)c2occc2c1
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 51.1 %

Procedure:
A solution of 1.1 gm (4.31 mMol) 5-(methoxycarbonyl)-7-bromobenzofuran in 20 ml dichloromethane was cooled to −78° C. To this solution were then added 2.7 ml (15.1 mMol) diisobutylaluminum hydride. The reaction mixture was allowed to warm to room temperature and was then stirred for 10 minutes. To the reaction mixture were then added 2.5 gm sodium fluoride and 815 μL water. The resulting mixture was diluted with an additional 10 ml dichloromethane and was then stirred for about 1 hour. The suspension was filtered and the filtrate concentrated under reduced pressure to provide 0.50 gm (51%) of the desired compound. The recovered solid was partitioned between 200 ml ethyl acetate and 100 ml Rochelle's Salt solution for 2 hours. This mixture was filtered, the phases separated, and the organic phase concentrated under reduced pressure to provide an additional 0.30 gm (31%) of the desired compound.
Reaction SMILES: [F:1][C:2]([F:10])([F:9])[S:3][CH2:4][C:5](=[N:7][OH:8])[CH3:6].[CH3:11][N:12]=[C:13]=[O:14]>C(N(CC)CC)C.ClCCl>[CH3:11][NH:12][C:13]([O:8][N:7]=[C:5]([CH3:6])[CH2:4][S:3][C:2]([F:10])([F:9])[F:1])=[O:14]
Reactant: CN=C=O
Reactant: CC(CSC(F)(F)F)=NO
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CNC(=O)ON=C(C)CSC(F)(F)F

Procedure:
A mixture of 1-trifluoromethylthio-2-propanone oxime (0.02 mole) from Step 2, methyl isocyanate (0.22 mole) and 2 drops of triethylamine in 25 ml of dichloromethane was heated at its reflux temperature overnight. The solvent was removed by evaporation under vacuum. The residual oil was recrystallized from a mixture of petroleum ether and diethyl ether to give a pure sample of 1-trifluoromethylthio-2-propanone O-methylcarbamoyl oxime, m.p. 56°-58°C. The structure of the product was confirmed by elemental and spectral analyses.