Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]([NH:8][C@H:9]([C:11]2[N:16]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[C:15](=[O:23])[C:14]3=[C:24]([CH3:27])[CH:25]=[CH:26][N:13]3[N:12]=2)[CH3:10])[C:3]=1Br.[OH:29][C:30]1[CH:47]=[CH:46][C:33]([C:34]([NH:36][C:37]2[CH:38]=[C:39](B(O)O)[CH:40]=[N:41][CH:42]=2)=[O:35])=[CH:32][CH:31]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C(OCC)(=O)C>[NH2:1][C:2]1[C:3]([C:39]2[CH:38]=[C:37]([NH:36][C:34](=[O:35])[C:33]3[CH:46]=[CH:47][C:30]([OH:29])=[CH:31][CH:32]=3)[CH:42]=[N:41][CH:40]=2)=[C:4]([NH:8][C@H:9]([C:11]2[N:16]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[C:15](=[O:23])[C:14]3=[C:24]([CH3:27])[CH:25]=[CH:26][N:13]3[N:12]=2)[CH3:10])[N:5]=[CH:6][N:7]=1
Reactant: O=C(Nc1cncc(B(O)O)c1)c1ccc(O)cc1
Reactant: Cc1ccn2nc([C@H](C)Nc3ncnc(N)c3Br)n(-c3ccccc3)c(=O)c12
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: C1COCCO1
Solvent: CCOC(C)=O
Product: Cc1ccn2nc([C@H](C)Nc3ncnc(N)c3-c3cncc(NC(=O)c4ccc(O)cc4)c3)n(-c3ccccc3)c(=O)c12
Temperature: 100 °C
Reaction time: 18 h
Yield: 22 %

Procedure:
To a solution of (S)-2-(1-((6-amino-5-bromopyrimidin-4-yl)amino)ethyl)-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4(3H)-one (100 mg, 0.23 mmol) were added (5-(4-hydroxybenzamido)pyridin-3-yl)boronic acid (88 mg, 0.34 mmol), 1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (19 mg, 0.02 mmol) and 227 μl of a 2M aqueous solution of cesium carbonate in dioxane (2 ml). The mixture was stirred under argon atmosphere at 100° C. for 18 hours and then diluted with ethyl acetate. The resulting solution was washed with water and brine, dried over magnesium sulphate, filtered and the solvents were removed under reduced pressure. The crude was purified by reverse phase using SP1® Purification System to give 29 mg (21% yield) of the title compound as a white solid. Purity 96%.
Reaction SMILES: [F:1][C:2]([F:7])([F:6])[C@H:3]([OH:5])[CH3:4].[H-].[Na+].BrC[C:12]1[CH:13]=[C:14]([B:18]([OH:20])[OH:19])[CH:15]=[CH:16][CH:17]=1.O>CN(C)C=O>[F:1][C:2]([F:7])([F:6])[C@H:3]([O:5][C:12]1[CH:13]=[C:14]([B:18]([OH:20])[OH:19])[CH:15]=[CH:16][CH:17]=1)[CH3:4]
Reactant: OB(O)c1cccc(CBr)c1
Reactant: C[C@@H](O)C(F)(F)F
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: C[C@@H](Oc1cccc(B(O)O)c1)C(F)(F)F
Temperature: 25 °C
Reaction time: 2 h
Yield: 135 %

Procedure:
A solution of (R)-1,1,1-trifluoropropan-2-ol (212 mg) in N,N-dimethylformamide (1.5 ml) was cooled to 0° C., sodium hydride (74 mg, 60 wt. % oil dispersion) and 3-(bromomethyl)phenyl boronic acid (100 mg) were sequentially added thereto, and the mixture was stirred at room temperature for 2 hours. To this reaction mixture were added water and an 1M aqueous solution of hydrochloric acid, and the mixture was extracted with ethyl acetate. This organic layer was washed with water and a saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulfate, and then concentrated under reduced pressure to give the titled compound (147 mg).
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[CH:4][C:5]2[O:9][C:8](S)=[N:7][C:6]=2[CH:11]=1.CN(C=O)C.S(Cl)([Cl:19])=O>>[Cl:19][C:8]1[O:9][C:5]2[CH:4]=[CH:3][C:2]([CH3:1])=[CH:11][C:6]=2[N:7]=1
Reactant: Cc1ccc2oc(S)nc2c1
Reactant: O=S(Cl)Cl
Solvent: CN(C)C=O
Product: Cc1ccc2oc(Cl)nc2c1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
Subsequently, the 5-methyl-2-mercaptobenzoxazole (6.2 g, 38 mmol) was dissolved in thionyl chloride (36.9 mL) and 2.79 mL of DMF was added. The reaction mixture was then stirred at r.t. for 30 min. The solvent was removed under reduced pressure and to the residue was added toluene (2×60 mL) followed by evaporation each time to remove excess SOCl2 via an azetrope. The resultant crude product was dissolved in ethyl acetate (100 mL), washed with water (100 mL) and dried over Na2SO4. Evaporation of ethyl acetate gave crude 22 which was purified by silica-gel column chromatography (eluent: petroleum ether) to provide pure 2-chloro-5-methylbenzoxazole, compound 22, (3.5 g, 58%).
Reaction SMILES: [OH-].[Na+].[CH2:3]([OH:10])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[O:11]=[CH:12][C:13](=[CH2:15])[CH3:14].[BH4-].[Na+]>O>[CH2:3]([O:10][CH2:14][CH:13]([CH3:15])[CH2:12][OH:11])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1
Reactant: OCc1ccccc1
Reactant: C=C(C)C=O
Agent: [BH4-]
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: CC(CO)COCc1ccccc1
Temperature: -10 °C
Reaction time: 0.5 h

Procedure:
A solution of 1.59 g. of sodium hydroxide and 1.6 ml. of water in 402 ml. (420 g; 3.89 moles) of benzyl alcohol was stirred and cooled to -10° C. while 100 ml. (83.7 g.; 1.19 moles) of freshly distilled methacrolein were added dropwise keeping the temperature between -10° C. and -5° C. After the reaction mixture had stirred for 0.5 hr. at -10° C., a solution of 44.9 g. (1.19 moles) of sodium borohydride in 180 ml. of water was added dropwise over 1.75 hr. keeping the temperature below 5° C. Stirring was continued for an additional hour during which time the reaction mixture was allowed to warm to room temperature. The resulting mixture was poured into ice-water and the organic materials were extracted several times with ether. The ether extracts were worked up by first combining the extracts washing with saturated brine and drying over anhydrous magnesium sulfate. After filtration and removal of the solvents in vacuo, the residue was carefully fractionated, giving, after removal of low boiling materials, 39.6 g. of rac. 3-benzyloxy-2-methyl-1-propanol as a colorless liquid, b.p. 91°-98° C. (0.5 mm Hg.).
Reaction SMILES: [CH3:1][N:2]([CH3:28])[C:3]1([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH2:8][CH2:7][C:6]([CH2:10][CH2:11][CH2:12][C:13]#[C:14][Si:15]([CH2:20][CH3:21])([CH2:18][CH3:19])[CH2:16][CH3:17])([OH:9])[CH2:5][CH2:4]1.I[NH:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1.C(=O)([O-])[O-].[Na+].[Na+]>C(C1C=CC=C(C(C)C)C=1N1C=CN(C2C(C(C)C)=CC=CC=2C(C)C)C1=[Pd-2](Cl)C1C(Cl)=CC=CN=1)(C)C>[CH3:28][N:2]([CH3:1])[C:3]1([C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=2)[CH2:8][CH2:7][C:6]([CH2:10][CH2:11][CH2:12][C:13]2[C:36]3[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=3)[NH:30][C:14]=2[Si:15]([CH2:20][CH3:21])([CH2:18][CH3:19])[CH2:16][CH3:17])([OH:9])[CH2:5][CH2:4]1
Reactant: INc1ccccc1
Reactant: CC[Si](C#CCCCC1(O)CCC(c2ccccc2)(N(C)C)CC1)(CC)CC
Agent: CC(C)c1cccc(C(C)C)c1-n1ccn(-c2c(C(C)C)cccc2C(C)C)c1=[Pd-2](Cl)c1ncccc1Cl
Agent: O=C([O-])[O-]
Agent: [Na+]
Product: CC[Si](CC)(CC)c1[nH]c2ccccc2c1CCCC1(O)CCC(c2ccccc2)(N(C)C)CC1
Temperature: 100 °C
Reaction time: 18 h

Procedure:
A mixture of 4-dimethylamino-4-phenyl-1-(5-triethylsilanyl-pent-4-inyl)cyclohexanol (504 mg, 1.26 mmol), iodoaniline (331 mg, 1.51 mmol), [1,3-bis-(2,6-diisopropylphenyl)-imidazol-2-ylidene]-(3-chloropyridyl)palladium(II)-chloride (PEPPSI, 171 mg, 0.25 mmol) and sodium carbonate (668 mg, 6.3 mmol) was evacuated for 30 min (oil pump). It was then flushed with argon and absolute N,N-dimethylformamide (5 mL, previously flushed for 1 h with argon) was added by syringe via a Schlenk tube. The mixture was stirred for 18 h at 100° C. and changed colour to dark brown during this. The reaction mixture was then concentrated to low volume in a vacuum, the residue taken up several times in toluol (3×10 mL) and concentrated to low volume again in each case, distributed between water and ethyl acetate (20 mL each) and the phases separated again. The aqueous phase was extracted with ethyl acetate (2×30 mL), the combined organic phases were washed with 1 M sodium thiosulphate solution (30 mL) and saturated sodium chloride solution (50 mL), dried with sodium sulphate and concentrated to low volume in a vacuum. The raw product (750 mg) was purified by means of flash chromatography (38 g, 20×2.5 cm) with chloroform/methanol (97:3). The mixed fractions (489 mg) obtained were purified once again by means of MPLC [LiChroprep Si60 (15-25 μm), 130 g, 46×2.6 cm] also with chloroform/methanol (97:3).
Reaction SMILES: Cl[C:2]1[N:7]=[CH:6][N:5]=[C:4]([NH2:8])[CH:3]=1.C(N(C(C)C)CC)(C)C.[N:18]1([CH2:23][CH2:24][N:25]2[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]2)[CH2:22][CH2:21][CH2:20][CH2:19]1>C(O)CCC>[N:18]1([CH2:23][CH2:24][N:25]2[CH2:26][CH2:27][N:28]([C:2]3[N:7]=[CH:6][N:5]=[C:4]([NH2:8])[CH:3]=3)[CH2:29][CH2:30]2)[CH2:19][CH2:20][CH2:21][CH2:22]1
Reactant: C1CCN(CCN2CCNCC2)C1
Reactant: Nc1cc(Cl)ncn1
Solvent: CCN(C(C)C)C(C)C
Solvent: CCCCO
Product: Nc1cc(N2CCN(CCN3CCCC3)CC2)ncn1
Temperature: 125 °C
Reaction time: 18 h

Procedure:
6-Chloropyrimidin-4-amine 7-2 (0.317 g, 2.44 mmol) and diisopropylethylamine (0.0.316 g, 2.44 mmol) were suspended in n-butanol and 1-(2-pyrrolidin-1-ylethyl)piperazine 11-1 (0.448 g, 2.44 mmol) was added. The reaction was stirred at 125° C. for 18 hours. Upon cooling the reaction was purified on a silica column (DCM:MeOH:NH4OH) to afford 11-2. 1NMR (CD3OD): 7.96 ppm (s, 1H); 5.71 ppm (s, 1H); 3.53 ppm (t, 4H); 2.69 ppm (m, 2H); 2.58 ppm (m, 10H); 1.82 ppm (m, 4H).
Reaction SMILES: [CH2:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][NH:2]1.[NH:11]1[C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=2[N:13]=[C:12]1[CH2:20][N:21]([CH2:32][C:33]1[CH:40]=[CH:39][C:36]([CH:37]=O)=[CH:35][CH:34]=1)[CH:22]1[C:31]2[N:30]=[CH:29][CH:28]=[CH:27][C:26]=2[CH2:25][CH2:24][CH2:23]1.CC(O)=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C1COCC1>[NH:11]1[C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=2[N:13]=[C:12]1[CH2:20][N:21]([CH2:32][C:33]1[CH:40]=[CH:39][C:36]([CH2:37][N:2]2[CH2:3][CH2:4][C:5]3[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=3)[CH2:1]2)=[CH:35][CH:34]=1)[CH:22]1[C:31]2[N:30]=[CH:29][CH:28]=[CH:27][C:26]=2[CH2:25][CH2:24][CH2:23]1
Reactant: c1ccc2c(c1)CCNC2
Reactant: O=Cc1ccc(CN(Cc2nc3ccccc3[nH]2)C2CCCc3cccnc32)cc1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: CC(=O)O
Solvent: C1CCOC1
Product: c1ccc2c(c1)CCN(Cc1ccc(CN(Cc3nc4ccccc4[nH]3)C3CCCc4cccnc43)cc1)C2
Temperature: 25 °C
Reaction time: 2 h
Yield: 78.4 %

Procedure:
Using General Procedure B: To a stirred solution of 1,2,3,4-tetrahydroisoquinoline (49 mg, 0.37 mmol), 4-{[(1H-benzimidazol-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-benzaldehyde (140 mg, 0.34 mmol), and AcOH 0.020 mL, 0.35 mmol) in THF (3.5 mL) was added NaBH(OAc)3 (94 mg, 0.44 mmol) and the mixture was stirred at room temperature for 2 h. Purification of the crude material by column chromatography on silica gel (500:5:1 CH2Cl2/MeOH/NH4OH) afforded a colourless foam (137 mg).
Reaction SMILES: [CH2:1]([C:8]#N)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH3:7].[CH3:10][NH:11][CH2:12][CH2:13][NH2:14].C(=S)=S>C(OCC)(=O)C>[CH3:10][N:11]1[CH2:12][CH2:13][N:14]=[C:8]1[CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH3:7]
Reactant: CNCCN
Reactant: CCCCCCCC#N
Solvent: S=C=S
Solvent: CCOC(C)=O
Product: CCCCCCCC1=NCCN1C
Temperature: 125 °C
Yield: 95.4 %

Procedure:
14.207 g (113.46 mmoles) of heptyl cyanide, 10.726 g (144.69 mmoles) of N-methylethylenediamine and 0.5 ml of carbon disulfide were mixed and heated at 125° C. for 24 hours. The solution was cooled, diluted with ethyl acetate and extracted with dilute hydrochloric acid. The acidic solution was basified with sodium hydroxide and extracted with ethyl acetate. The organic extracts were treated with charcoal, filtered, concentrated and Kugelrohr distilled at 105° C./1 2mm to give 19.73 g (77.3%) of the product.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([O:8]C)=[CH:4][C:3]=1[NH:10][C:11](N)=[S:12].C[Si](OP(=O)=O)(C)C.C(=O)(O)[O-].[Na+].[F:27][C:28]([F:33])([F:32])C(O)=O>>[F:1][C:2]1[C:3]2[N:10]=[C:11]([C:28]([F:33])([F:32])[F:27])[S:12][C:4]=2[C:5]([OH:8])=[CH:6][CH:7]=1
Reactant: O=C(O)C(F)(F)F
Reactant: COc1ccc(F)c(NC(N)=S)c1
Agent: C[Si](C)(C)OP(=O)=O
Agent: O=C([O-])O
Agent: [Na+]
Product: Oc1ccc(F)c2nc(C(F)(F)F)sc12
Temperature: 95 °C
Reaction time: 18 h

Procedure:
A mixture containing crude 3-amino-4-fluoro-2-sulfanylphenol (C15) (Step 1) and polyphosphoric acid trimethylsilyl ester (10 mL) in trifluoroacetic acid (20 mL) was stirred at 95° C. for 18 hours. After cooling to room temperature the reaction was treated with saturated aqueous sodium bicarbonate solution and extracted with dichloromethane (3×10 mL). The combined organic layers were dried over magnesium sulfate and concentrated in vacuo. Purification via silica gel chromatography (Gradient: 0% to 30% tert-butyl methyl ether in heptanes) afforded the title compound as a solid. Yield: 1.66 g, 7.0 mmol, 59%. GCMS m/z 237 (M+). 1H NMR (400 MHz, CD3OD) δ 6.90 (dd, J=8.7, 3.3 Hz, 1H), 7.21 (dd, J=10.2, 8.7 Hz, 1H).
Reaction SMILES: [CH:1]([C@H:4]1[NH:7][C:6](=[O:8])[C@H:5]1[O:9][Si:10]([CH2:15][CH3:16])([CH2:13][CH3:14])[CH2:11][CH3:12])([CH3:3])[CH3:2].[C:17](Cl)(=[O:24])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.C(N(C(C)C)CC)(C)C>CN(C)C1C=CN=CC=1.C(Cl)Cl>[C:17]([N:7]1[C@H:4]([CH:1]([CH3:2])[CH3:3])[C@H:5]([O:9][Si:10]([CH2:15][CH3:16])([CH2:13][CH3:14])[CH2:11][CH3:12])[C:6]1=[O:8])(=[O:24])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1
Reactant: CC[Si](CC)(CC)O[C@@H]1C(=O)N[C@@H]1C(C)C
Reactant: O=C(Cl)c1ccccc1
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CC[Si](CC)(CC)O[C@@H]1C(=O)N(C(=O)c2ccccc2)[C@@H]1C(C)C
Temperature: 0 °C
Reaction time: 6 h

Procedure:
A solution of (±)-cis-4-isopropyl-3-triethylsilyloxy-azetidin-2-one (486 mg, 2.00 mmole), benzoyl chloride (0.255 mL, 1.1 equiv), diisopropylethyl amine (0.346 mL, 1.2 equiv) and p-dimethylaminopyridine (244 mg, 1 equiv) in dry DCM (6 mL) was left stirring at 0° C. for 6 hr. The bath was removed and the reaction was left stirring overnight. It was then diluted with DCM and washed with water, aq. HCl solution (0.1 N), saturated aq. NaHCO3 solution, brine and dried (Na2SO4). Removal of the solvent followed by silica gel column chromatography (gradient elution with 0 to 5% EtOAc in hexane) gave the title compound: 1H NMR δ (CDCl3) 0.47-0.94 (m, 21H), 2.09 (m, 1H), 4.07 (m, 1H), 4.75 (m, 1H), 7.24-7.76 (m, 5H).
Reaction SMILES: C(Cl)Cl.[SH:4][C:5]1[S:6][C:7]2[CH2:13][CH2:12][CH2:11][CH2:10][C:8]=2[N:9]=1.Br[CH:15]([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[C:16]([OH:18])=[O:17]>C(N(CC)CC)C>[C:19]1([CH:15]([S:4][C:5]2[S:6][C:7]3[CH2:13][CH2:12][CH2:11][CH2:10][C:8]=3[N:9]=2)[C:16]([OH:18])=[O:17])[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1
Reactant: Sc1nc2c(s1)CCCC2
Reactant: O=C(O)C(Br)c1ccccc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: O=C(O)C(Sc1nc2c(s1)CCCC2)c1ccccc1
Yield: 77 %

Procedure:
A methylene chloride solution of 5.13 g (0.03 m) 2-mercapto-4,5,6,7-tetrahydrobenzothiazole, 6.45 g. (0.03 m) α-bromophenylacetic acid and 6.0 g (0.06 m) triethylamine is heated to gentle reflux overnight. The solution is extracted twice with a dilute hydrochloric acid solution, once with water and is then dried over anhydrous MgSO4. The residual solid after solvent removal is recrystallized from acetonitrile. 7.0 g (77% yield) of title compound, melting at 118°-20° C., is obtained
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]2[CH:10]=[C:9]([C:11]3[C:19]4[C:14](=[CH:15][C:16]([O:22][CH3:23])=[C:17]([O:20][CH3:21])[CH:18]=4)[N:13]([CH2:24][CH2:25]I)[CH:12]=3)[N:8]([S:27]([C:30]3[CH:35]=[CH:34][C:33]([CH3:36])=[CH:32][CH:31]=3)(=[O:29])=[O:28])[C:5]2=[N:6][CH:7]=1.C(=O)([O-])[O-].[K+].[K+].[CH3:43][N:44]1[CH2:49][CH2:48][NH:47][CH2:46][CH2:45]1>C(#N)C>[CH3:21][O:20][C:17]1[CH:18]=[C:19]2[C:14](=[CH:15][C:16]=1[O:22][CH3:23])[N:13]([CH2:24][CH2:25][N:47]1[CH2:48][CH2:49][N:44]([CH3:43])[CH2:45][CH2:46]1)[CH:12]=[C:11]2[C:9]1[N:8]([S:27]([C:30]2[CH:35]=[CH:34][C:33]([CH3:36])=[CH:32][CH:31]=2)(=[O:29])=[O:28])[C:5]2=[N:6][CH:7]=[C:2]([F:1])[CH:3]=[C:4]2[CH:10]=1
Reactant: CN1CCNCC1
Reactant: COc1cc2c(-c3cc4cc(F)cnc4n3S(=O)(=O)c3ccc(C)cc3)cn(CCI)c2cc1OC
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: COc1cc2c(-c3cc4cc(F)cnc4n3S(=O)(=O)c3ccc(C)cc3)cn(CCN3CCN(C)CC3)c2cc1OC
Yield: 86.9 %

Procedure:
But using 1 g of 5-fluoro-2-[1-(2-iodoethyl)-5,6-dimethoxy-1H-indol-3-yl]-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine, 0.223 g of potassium carbonate and 0.323 g of 1-methylpiperazine in 100 ml of acetonitrile. 0.83 g of 2-[5,6-dimethoxy-1-[2-(4-methylpiperazin-1-yl)ethyl]-1H-indol-3-yl]-5-fluoro-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine is thus obtained in the form of a solid, the characteristics of which are as follows:
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6]([C:8]#[C:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[CH2:16][C:17]([NH2:19])=[O:18])[C:5]([CH3:20])=[CH:4][N:3]=1>CN(C=O)C.CO.[Pt]=O>[Cl:1][C:2]1[N:7]=[C:6]([CH2:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[CH2:16][C:17]([NH2:19])=[O:18])[C:5]([CH3:20])=[CH:4][N:3]=1
Reactant: Cc1cnc(Cl)nc1C#Cc1ccccc1CC(N)=O
Agent: O=[Pt]
Solvent: CO
Solvent: CN(C)C=O
Product: Cc1cnc(Cl)nc1CCc1ccccc1CC(N)=O
Reaction time: 40 h

Procedure:
A suspension of 2-(2-((2-chloro-5-methylpyrimidin-4-yl)ethynyl)phenyl)acetamide (I9) (5.01 g, 17.5 mmol) in DMF (231 mL) and MeOH (80 mL) containing platinum oxide (0.995 g, 4.38 mmol) was stirred under a hydrogen atmosphere for 40 hours. The resulting mixture was filtered through a pad of Celite and the filtrate concentrated in vacuo. The resulting residue was diluted with ice water (400 mL) to give a precipitate, which was filtered and dried to give the title compound K6 (4.23 g, 83%); 1H NMR (300 MHz, d6-DMSO) δ 8.47 (s, 1H), 7.44 (brs, 1H), 7.21-7.24 (m, 1H), 7.12-7.15 (m, 3H), 6.92 (brs, 1H), 3.47 (s, 2H), 2.99 (s, 4H), 2.15 (s, 3H). LCMS-B: rt 5.528 min; m/z 290 [M+H]+.
Reaction SMILES: [OH:1][CH2:2][C:3]1[CH:4]=[C:5]([CH:8]=[CH:9][CH:10]=1)[C:6]#[N:7].Cl[C:12]1[CH:13]=[C:14]2[N:21](C(OC(C)(C)C)=O)[C@@H:20]([CH3:29])[CH2:19][N:15]2[C:16](=[O:18])[N:17]=1>>[CH3:29][C@H:20]1[CH2:19][N:15]2[C:16](=[O:18])[N:17]=[C:12]([O:1][CH2:2][C:3]3[CH:4]=[C:5]([CH:8]=[CH:9][CH:10]=3)[C:6]#[N:7])[CH:13]=[C:14]2[NH:21]1
Reactant: C[C@H]1Cn2c(cc(Cl)nc2=O)N1C(=O)OC(C)(C)C
Reactant: N#Cc1cccc(CO)c1
Product: C[C@H]1Cn2c(cc(OCc3cccc(C#N)c3)nc2=O)N1

Procedure:
The title compound was prepared by a procedure similar to that described for E9 starting from 3-(hydroxymethyl)benzonitrile and (S)-tert-butyl 7-chloro-2-methyl-5-oxo-2,3-dihydroimidazo[1,2-c]pyrimidine-1(5H)-carboxylate.
Reaction SMILES: [N:1]([C:4]1[C:24](=[O:25])[CH2:23][CH2:22][C@@:21]2([CH3:26])[C:5]=1[CH2:6][CH2:7][C@@H:8]1[C@@H:20]2[CH2:19][CH2:18][C@@:17]2([CH3:27])[C@H:9]1[CH2:10][CH2:11][C@@H:12]2[C@H:13]([CH3:16])[CH2:14][OH:15])=[N+]=[N-].O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>O1CCCC1>[NH2:1][C:4]1[C:24](=[O:25])[CH2:23][CH2:22][C@@:21]2([CH3:26])[C:5]=1[CH2:6][CH2:7][C@@H:8]1[C@@H:20]2[CH2:19][CH2:18][C@@:17]2([CH3:27])[C@H:9]1[CH2:10][CH2:11][C@@H:12]2[C@H:13]([CH3:16])[CH2:14][OH:15]
Reactant: C[C@H](CO)[C@H]1CC[C@H]2[C@@H]3CCC4=C(N=[N+]=[N-])C(=O)CC[C@]4(C)[C@H]3CC[C@]12C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Solvent: O
Product: C[C@H](CO)[C@H]1CC[C@H]2[C@@H]3CCC4=C(N)C(=O)CC[C@]4(C)[C@H]3CC[C@]12C

Procedure:
To a stirred solution of (20S)-4-azido-21-hydroxy-20-methylpregn-4-en-3-one (3.15 mmole) in tetrahydrofuran (20 mL)-water (7 mL) was added triphenylphosphine (1.41 g, 5.38 mmole). The reaction was heated at reflux temperature for 16 hours. Most of the tetrahydrofuran was removed under vacuum. Dichloromethane was added to the mixture and the organic solution was placed atop a column of silica gel and flash chromatographed (hexane-30% ethyl acetate). The fractions containing the product were combined and concentrated to a white solid which was crystallized from diethyl ether to give (20S)-4-amino-21-hydroxy-20-methylpregn-4-en-3-one. IR 3510, 3470, 3384, 1648, 1614, 1576 cm-1 ; MS (CI) 346 (100%, M+ +1) (EI) 345 (65%, M+), 302 (100%); 1H NMR δ (CDCl3) 0.73 (3H, s, C18 -Me), 1.04 (d, C21 -Me), 1.15 (s, C19 -Me), 2.42-2.56 (3H m) 3.73 (v br NH2) 3.36 (1H dd 1/2 C21 -CH2), 3.63 (1H, dd, 1/2 C21 -CH2); 13C NMR δ (CDCl3) 132.85, 139.15, 194.38. This compound has the following structure: ##STR4##
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][N:5]1[C:17]2[CH:16]=[C:15]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[C:14]3[C:24](=[O:28])[NH:25][C:26](=[O:27])[C:13]=3[C:12]=2[C:11]2[CH:10]=[C:9]([OH:29])[CH:8]=[CH:7][C:6]1=2.[CH3:30][NH:31][CH3:32].Cl.C(=O)([O-])[O-].[K+].[K+]>CC(N(C)C)=O.O>[CH3:30][N:31]([CH3:32])[CH2:2][CH2:3][CH2:4][N:5]1[C:17]2[CH:16]=[C:15]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[C:14]3[C:24](=[O:28])[NH:25][C:26](=[O:27])[C:13]=3[C:12]=2[C:11]2[CH:10]=[C:9]([OH:29])[CH:8]=[CH:7][C:6]1=2
Reactant: CNC
Reactant: O=C1NC(=O)c2c1c(-c1ccccc1)cc1c2c2cc(O)ccc2n1CCCBr
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CC(=O)N(C)C
Product: CN(C)CCCn1c2ccc(O)cc2c2c3c(c(-c4ccccc4)cc21)C(=O)NC3=O
Temperature: 80 °C
Reaction time: 18 h
Yield: 47 %

Procedure:
To a solution of bromide (204) prepared as described in example 173 (0.12 g, 0.27 mmol) in dimethylacetamide (4 mL) was added the amine, dimethylamine (25 mol eq., 0.85 mL in this case as an 40% aqueous solution). The reaction vessel was sealed and heated at 80° C. with stirring for 18 h, before being diluted with water. The resulting solution was then acidified by the dropwise addition of concentrated hydrochloric acid and the pH was then adjusted to approximately pH=9 by the addition of solid potassium carbonate. The precipitated product was either collected by filtration and washed with water and diisopropyl ether before being dried or extracted with ethyl acetate. The organic layer was dried, the drying agent was removed and the solution was concentrated to dryness. Chromatography on silica eluting with methanol/dichloromethane (1:9 to 1:4), followed by trituration in ethyl acetate/hexane gave amine (208) (52 mg, 47%) as a yellow powder, mp 185–189° C. 1H NMR δ [(CD3)2SO] 11.05 (s, 1H), 9.34 (s, 1H), 8.41 (d, J=2.4 Hz, 1H), 7.78 (s, 1H), 7.64 (m, 2H), 7.56 (d, J=8.9 Hz, 1H), 7.47 (m, 3H), 7.14 (dd, J=8.9, 2.4 Hz, 1H), 4.48 (t, J=6.6 Hz, 2H), 2.16 (t, J=6.5 Hz, 2H), 2.08 (s, 6H), 1.90 (m, 2H). Found: C, 71.98; H, 5.67; N, 10.14. C25H23N3O3.1/4H2O requires: C, 71.84; H, 5.67; N, 10.05.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:20]=[CH:19][C:18]3[CH2:17][N:16](C(OC(C)(C)C)=O)[CH2:15][CH2:14][C:13]=3[N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1.[C:28]([O:31][CH2:32][C:33]1[C:38](B2OC(C)(C)C(C)(C)O2)=[CH:37][CH:36]=[CH:35][C:34]=1[N:48]1[CH2:53][CH2:52][C:51]2[C:54]3[CH2:60][CH2:59][CH2:58][CH2:57][C:55]=3[S:56][C:50]=2[C:49]1=[O:61])(=[O:30])[CH3:29].C([O-])([O-])=O.[Na+].[Na+].COCCOC>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.C(Cl)Cl>[C:28]([O:31][CH2:32][C:33]1[C:38]([C:2]2[CH:3]=[C:4]([NH:10][C:11]3[CH:20]=[CH:19][C:18]4[CH2:17][NH:16][CH2:15][CH2:14][C:13]=4[N:12]=3)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=2)=[CH:37][CH:36]=[CH:35][C:34]=1[N:48]1[C:49](=[O:61])[C:50]2[S:56][C:55]3[CH2:57][CH2:58][CH2:59][CH2:60][C:54]=3[C:51]=2[CH2:52][CH2:53]1)(=[O:30])[CH3:29]
Reactant: Cn1cc(Br)cc(Nc2ccc3c(n2)CCN(C(=O)OC(C)(C)C)C3)c1=O
Reactant: CC(=O)OCc1c(B2OC(C)(C)C(C)(C)O2)cccc1N1CCc2c(sc3c2CCCC3)C1=O
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: COCCOC
Solvent: ClCCl
Product: CC(=O)OCc1c(-c2cc(Nc3ccc4c(n3)CCNC4)c(=O)n(C)c2)cccc1N1CCc2c(sc3c2CCCC3)C1=O

Procedure:
To a microwave tube equipped with a stirring bar, 158c (300 mg, 0.689 mmol), boronic ester 111a (365 mg, 0.758 mmol), Pd(PPh3)4 (39.8 mg, 0.034 mmol), Na2CO3 aqueous solution (1.0 N, 2.27 mL. 2.27 mmol), 1,2-dimethoxyethane (3.0 mL) were added. The mixture was reacted in microwave at 130° C. for 10 min. methylene chloride (200 mL) was added and the resulting mixture was washed with water (30 mL×3), brine (30 mL×1), dried over MgSO4, filtered, and removed solvent in vacuo. Silica gel column chromatography (MeOH:methylene chloride=5:95) gave 158d.