Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([CH:3]([CH:7]([NH:10][C:11](=[O:19])[CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[C:8]#[CH:9])[C:4]([OH:6])=[O:5])[CH3:2].[OH-].[Na+].CC1(C)S[C@@H]2[C@H](NC(CC3C=CC=CC=3)=O)C(=O)N2[C@H]1C(O)=O>P([O-])([O-])([O-])=O>[CH2:1]([C@@H:3]([CH:7]([NH:10][C:11](=[O:19])[CH2:12][C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1)[C:8]#[CH:9])[C:4]([OH:6])=[O:5])[CH3:2]
Reactant: C#CC(NC(=O)Cc1ccccc1)C(CC)C(=O)O
Agent: CC1(C)S[C@@H]2[C@H](NC(=O)Cc3ccccc3)C(=O)N2[C@H]1C(=O)O
Agent: O=P([O-])([O-])[O-]
Agent: [Na+]
Product: C#CC(NC(=O)Cc1ccccc1)[C@H](CC)C(=O)O
Temperature: 25 °C
Reaction time: 48 h

Procedure:
Racemic ethyl 3-(phenylacetamido)-4-pentynoic acid (400 mg) was suspended in phosphate buffer (100 mL, 0.01 molar, prepared from 0.1 molar pH 7.24 solution obtained from sigma). The pH of the solution was adjusted between 8.0 to 8.2 using dilute sodium hydroxide. Under slow stirring, 100 units of immobilized penicillin G acylase (Boehringer-Mannheim) was added. The reaction mixture was stirred at room temperature for 48 hours, the pH was adjusted to 3.0, and then extracted with ethyl acetate (3×50 mL). The organic extracts were combined, dried over magnesium sulfate, filtered and evaporated to give the desired amide, (S)-ethyl-3-(phenylacetamido)-4-pentynoic acid.
Reaction SMILES: [CH2:1]([O:8][C:9]([C:11]([CH3:23])([CH3:22])[CH2:12][O:13][C:14]1[CH:21]=[CH:20][C:17]([CH:18]=[O:19])=[CH:16][CH:15]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[BH4-].[Na+].Cl>O1CCCC1>[CH2:1]([O:8][C:9]([C:11]([CH3:23])([CH3:22])[CH2:12][O:13][C:14]1[CH:15]=[CH:16][C:17]([CH2:18][OH:19])=[CH:20][CH:21]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CC(C)(COc1ccc(C=O)cc1)C(=O)OCc1ccccc1
Agent: Cl
Agent: [BH4-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CC(C)(COc1ccc(CO)cc1)C(=O)OCc1ccccc1
Temperature: 25 °C
Reaction time: 3 h
Yield: 97.3 %

Procedure:
To a solution of 4-(2-benzyloxycarbonyl-2-methyl-propoxy)benzaldehyde (0.97 g) in tetrahydrofuran (20 mL) was added sodium borohydride (59 mg), and the mixture was stirred at room temperature for 3 hours. The reaction mixture was poured into 0.5 mol/L hydrochloric acid, and the resulting mixture was extracted with diethyl ether. The organic layer was washed with water and brine successively, and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=6/1-3/2) to give the title compound (0.95 g).
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[N:8]=[C:9]([CH2:11][CH2:12][CH3:13])[NH:10][C:3]=12.[H-].[Na+].Br[CH2:17][C:18]1[CH:23]=[CH:22][C:21]([CH2:24][CH:25]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[C:26]#[N:27])=[CH:20][CH:19]=1>CN(C=O)C>[C:26]([CH:25]([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[CH2:24][C:21]1[CH:22]=[CH:23][C:18]([CH2:17][N:8]2[C:4]3=[N:5][CH:6]=[CH:7][C:2]([CH3:1])=[C:3]3[N:10]=[C:9]2[CH2:11][CH2:12][CH3:13])=[CH:19][CH:20]=1)#[N:27]
Reactant: CCCc1nc2nccc(C)c2[nH]1
Reactant: N#CC(Cc1ccc(CBr)cc1)c1ccccc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCCc1nc2c(C)ccnc2n1Cc1ccc(CC(C#N)c2ccccc2)cc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 19.1 %

Procedure:
To a solution of 7-methyl-2-propylimidazo [4,5-b]pyridine (106 mg, 0.61 mmol) in DMF (3 mL) was added NaH (0.91 mmol). The suspension was stirred at room temperature for 30 minutes, at which time a solution of the product of Step D (200 mg, 0.667 mmol) in DMF (2 mL) was added. The mixture was stirred for 2 hours at room temperature, quenched with water, and then concentrated in vacuo. The residue was partitioned between water and EtOAc, and the combined organic layers were washed with brine, dried (K2CO3), filtered, and evaporated in vacuo. The residue was chromatographed on a silica gel flash chromatography column eluted with 50% ethyl acetate/hexane to afford 46 mg (19%) of the title compound.
Reaction SMILES: C[O:2][C:3](=[O:29])[C@@H:4]([O:26][CH2:27][CH3:28])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][CH2:13][C:14]2[N:15]=[C:16]([C:20]([CH3:23])([CH3:22])[CH3:21])[O:17][C:18]=2[CH3:19])=[CH:8][C:7]=1[CH2:24][CH3:25].[Li+].[OH-]>>[C:20]([C:16]1[O:17][C:18]([CH3:19])=[C:14]([CH2:13][O:12][C:9]2[CH:10]=[CH:11][C:6]([CH2:5][C@H:4]([O:26][CH2:27][CH3:28])[C:3]([OH:29])=[O:2])=[C:7]([CH2:24][CH3:25])[CH:8]=2)[N:15]=1)([CH3:22])([CH3:23])[CH3:21]
Reactant: CCO[C@@H](Cc1ccc(OCc2nc(C(C)(C)C)oc2C)cc1CC)C(=O)OC
Agent: [Li+]
Agent: [OH-]
Product: CCO[C@@H](Cc1ccc(OCc2nc(C(C)(C)C)oc2C)cc1CC)C(=O)O

Procedure:
In analogy to the procedure described in example 46 d], (S)-3-[4-(2-tert-butyl-5-methyl-oxazol-4-ylmethoxy)-2-ethyl-phenyl]-2-ethoxy-propionic acid methyl ester was treated with LiOH to obtain (S)-3-[4-(2-tert-butyl-5-methyl-oxazol-4-ylmethoxy)-2-ethyl-phenyl]-2-ethoxy-propionic acid as colorless solid.
Reaction SMILES: [CH3:1][C:2]1[C:6]([C:7]2[C:8]([C:15]3[CH:20]=[CH:19][C:18]([O:21]C)=[CH:17][CH:16]=3)=[N:9][N:10]([CH3:14])[C:11]=2[CH:12]=[O:13])=[C:5]([CH3:23])[O:4][N:3]=1.Cl.NO.N1C=CC=CC=1.Cl>C(O)C.C(Cl)Cl>[CH3:1][C:2]1[C:6]([C:7]2[C:8]([C:15]3[CH:20]=[CH:19][C:18]([OH:21])=[CH:17][CH:16]=3)=[N:9][N:10]([CH3:14])[C:11]=2[CH2:12][OH:13])=[C:5]([CH3:23])[O:4][N:3]=1
Reactant: COc1ccc(-c2nn(C)c(C=O)c2-c2c(C)noc2C)cc1
Agent: Cl
Agent: NO
Solvent: CCO
Solvent: c1ccncc1
Solvent: ClCCl
Product: Cc1noc(C)c1-c1c(-c2ccc(O)cc2)nn(C)c1CO
Temperature: 100 °C

Procedure:
A mixture of 4-(3,5-dimethylisoxazol-4-yl)-3-(4-methoxyphenyl)-1-methyl-1H-pyrazole-5-carbaldehyde (45.0 mg, 0.14 mmol), hydroxylamine hydrochloride (100 mg, 1.45 mmol) and pyridine (129 μL, 1.59 mmol) in ethanol (1 mL) was heated at 100° C. for 3 minutes in the microwave. 1 mL 2 M HCl and 5 mL DCM were added. A precipitate was formed, which was found to be the desired product. The remaining solution was extracted with DCM (5×3 mL). The DCM layer was filtered through a phase separator and concentrated together with the precipitate to give the raw product. To this was added thionyl chloride (3 mL) and the mixture was stirred at room temperature for 2 h and concentrated. Dry DCM (1 mL) and BF3.Me2S (1 M solution in DCM, 0.5 mL, 0.5 mmol) were added and stirred at room temperature over night. The mixture was concentrated and MeOH was added to quench the reaction The crude product was purified on silica gel to give 4-(3,5-dimethylisoxazol-4-yl)-3-(4-hydroxyphenyl)-1-methyl-1H-pyrazole-5-carbonitrile (30.5 mg, 0.01 mmol, 68%), and 3-(3-chloro-4-hydroxyphenyl)-4-(3,5-dimethylisoxazol-4-yl)-1-methyl-1H-pyrazole-5-carbonitrile (6.0 mg, 0.018 mmol, 13%).
Reaction SMILES: [NH2:1][C@@H:2]([CH3:17])[C@@H:3]([C:5]1[CH:6]=[CH:7][C:8]([OH:16])=[C:9]([NH:11][S:12]([CH3:15])(=[O:14])=[O:13])[CH:10]=1)[OH:4].[CH3:18][C:19]1[CH:20]=[C:21]([CH:24]=[C:25]([CH3:27])[CH:26]=1)[CH:22]=O>CO>[CH3:18][C:19]1[CH:26]=[C:25]([CH:24]=[C:21]([CH3:22])[CH:20]=1)[CH2:27][NH:1][C@@H:2]([CH3:17])[C@@H:3]([C:5]1[CH:6]=[CH:7][C:8]([OH:16])=[C:9]([NH:11][S:12]([CH3:15])(=[O:14])=[O:13])[CH:10]=1)[OH:4]
Reactant: C[C@H](N)[C@H](O)c1ccc(O)c(NS(C)(=O)=O)c1
Reactant: Cc1cc(C)cc(C=O)c1
Solvent: CO
Product: Cc1cc(C)cc(CN[C@@H](C)[C@H](O)c2ccc(O)c(NS(C)(=O)=O)c2)c1
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 32.8 %

Procedure:
Borane-pyridine complex (160 μL, 1.50 mmol) was added to a methanol solution (5 mL) of an amine (3) (131 mg, 0.50 mmol) and 3,5-dimethylbenzaldehyde (90 μL, 0.65 mmol) at 40° C. and the mixture was stirred for 1.5 hours. The reaction mixture was allowed to cool to room temperature and extracted after addition of water with a mixed solvent (ethyl acetate: methanol=10:1), and the organic layer was washed with saturated aqueous sodium chloride solution. The organic layer was dried and concentrated, and the crude product obtained was purified by amine silica gel column chromatography (eluant:chloroform:methanol=7:1), to give a desired amine (8) as a white solid (62 mg, yield 33%).
Reaction SMILES: C[O:2][C:3]1[CH:8]=[CH:7][C:6]([S:9]([C:12]2[C:13]([NH:19][C:20]3[C:25]([CH3:26])=[CH:24][C:23]([CH3:27])=[CH:22][C:21]=3[CH3:28])=[N:14][C:15]([CH3:18])=[N:16][CH:17]=2)(=[O:11])=[O:10])=[CH:5][CH:4]=1.[Li+].[I-].N1C(C)=CC(C)=CC=1C>CCOCC>[CH3:18][C:15]1[N:14]=[C:13]([NH:19][C:20]2[C:25]([CH3:26])=[CH:24][C:23]([CH3:27])=[CH:22][C:21]=2[CH3:28])[C:12]([S:9]([C:6]2[CH:5]=[CH:4][C:3]([OH:2])=[CH:8][CH:7]=2)(=[O:11])=[O:10])=[CH:17][N:16]=1
Reactant: COc1ccc(S(=O)(=O)c2cnc(C)nc2Nc2c(C)cc(C)cc2C)cc1
Agent: [I-]
Agent: [Li+]
Solvent: Cc1cc(C)nc(C)c1
Solvent: CCOCC
Product: Cc1cc(C)c(Nc2nc(C)ncc2S(=O)(=O)c2ccc(O)cc2)c(C)c1
Temperature: 25 °C
Yield: 94.2 %

Procedure:
A mixture of [5-(4-methoxy-benzenesulfonyl)-2-methyl-pyrimidin-4-yl]-(2,4,6-trimethylphenyl)-amine (300 mg, 0.75 mmol), prepared as described in Example 1, LiI (2.0 g, 15 mmol) and 2,4,6-collidine (5 mL) was refluxed under N2 for 2 h and then cooled to room temperature. The reaction mixture was diluted with Et2O, and extracted (4×) with 2 N NaOH. The combined aqueous layers were washed with ether, neutralized with 3 N HCl to pH=7.0 and then were extracted three times with CH2Cl2. The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by chromatography on silica gel (50:50 hexanes/EtOAc) to provide the desired product (271 mg, 93%) as a white solid: mp 246–248° C.; 1H NMR (300 MHz, CDCl3) δ 8.69 (s, 1H), 8.30 (br s, 1H), 7.82 (d, J=8.7 Hz, 2H), 6.92 (s, 2H), 6.89 (d, J=8.7 Hz, 2H), 2.40 (s, 3H), 2.31 (s, 3H), 2.03 (s, 6H); APCI MS m/z 384 [(M+H)+, calcd for C20H22N3O3S, 384.1].
Reaction SMILES: [ClH:1].Cl.[N:3]1([CH:12]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH:13]([OH:22])[CH2:14][N:15]2CCN(C)[CH2:17][CH2:16]2)[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[CH:4]1.C(N)C>>[ClH:1].[CH2:16]([NH:15][CH2:14][CH:13]([OH:22])[CH:12]([N:3]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[CH:4]1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[CH3:17]
Reactant: CN1CCN(CC(O)C(c2ccccc2)n2ccc3ccccc32)CC1
Agent: CCN
Agent: Cl
Product: CCNCC(O)C(c1ccccc1)n1ccc2ccccc21

Procedure:
In an analogous manner to EXAMPLE 1, step 3, a solution of (2RS,3RS)-toluene-4-sulfonic acid 2-hydroxy-3-indol-1-yl-3-phenyl-propyl ester (EXAMPLE 1, step 3, 0.42 g, 1.0 mmol) and ethylamine (2 N solution in methanol, 5 mL) was stirred in a sealed flask at room temperature for 15 hours. After dilution with a saturated aqueous solution of sodium bicarbonate, the mixture was extracted with a solution of dichloromethane/isopropyl alcohol (3/1). The extract was washed with water, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The crude product was purified on via Biotage chromatography (FlasH40i, silica, dichloromethane, 5% methanol/dichloromethane) to give an oil as free base of the expected product. The free base was dissolved in a minimum amount of ethanol and treated with a 1 N ethereal solution of hydrochloric acid until the solution was pH=3 followed by diethyl ether. The product was then crystallized by adding a minimum amount ethyl acetate to afford the titled compound, (1RS,2SR)-3-(ethylamino)-1-(1H-indol-1-yl)-1-phenylpropan-2-ol hydrochloride as a tan solid. MS (ES) m/z 295.2 ([M+H]+); HRMS: calcd for C19H22N20+H+, 295.18049; found (ESI, [M+H]+), 295.1797.
Reaction SMILES: [NH2:1][C:2]1[C:7]([NH2:8])=[C:6]([NH:9][C@@H:10]2[C@@H:15]3[O:16][C@@H:12]([CH2:13][CH2:14]3)[C@@H:11]2[C:17]([NH2:19])=[O:18])[C:5]([Cl:20])=[CH:4][N:3]=1.[CH3:21][N:22]1[CH:26]=[C:25]([CH:27]=O)[CH:24]=[N:23]1.C([O-])(=O)C.[NH4+]>CCO>[Cl:20][C:5]1[C:6]([NH:9][C@@H:10]2[C@@H:15]3[O:16][C@@H:12]([CH2:13][CH2:14]3)[C@@H:11]2[C:17]([NH2:19])=[O:18])=[C:7]2[N:8]=[C:27]([C:25]3[CH:24]=[N:23][N:22]([CH3:21])[CH:26]=3)[NH:1][C:2]2=[N:3][CH:4]=1
Reactant: Cn1cc(C=O)cn1
Reactant: NC(=O)[C@@H]1[C@H](Nc2c(Cl)cnc(N)c2N)[C@H]2CC[C@@H]1O2
Agent: CC(=O)[O-]
Agent: [NH4+]
Solvent: CCO
Product: Cn1cc(-c2nc3c(N[C@H]4[C@@H](C(N)=O)[C@@H]5CC[C@H]4O5)c(Cl)cnc3[nH]2)cn1
Temperature: 70 °C

Procedure:
(1S,2R,3S,4R)-3-(2,3-diamino-5-chloropyridin-4-ylamino)-7-oxabicyclo[2.2.1]heptane-2-carboxamide (17) (90 mg, 0.302 mmol), 1-methyl-1H-pyrazole-4-carbaldehyde (30 mg, 0.272 mmol) were taken in EtOH (15 ml) to which ammonium acetate (35 mg) was added and the reaction mixture was heated at 70° C. for 48 h. Crude LCMS showed the desired product along with trace of starting material. The reaction mixture was allowed to come to rt and the precipitated was filtered and washed well with hot ethanol to afford the desired product (70 mg, 41%) as a white solid. NMR: δ (1H, 400M Hz, DMSO-d6): 1.40-1.80 (4H, m), 2.92 (1H, d, J=8.4 Hz), 3.92 (3H, s), 4.28 (1H, s), 4.56 (1H, s), 5.40-5.55 (1H, m), 6.82 (1H, s), 7.14 (1H, s), 7.1 (1H, s), 7.86 (1H, s), 7.99 (1H, s), 8.23 (1H, s).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[CH2:13][NH:14][C@H:15]1[CH2:20][CH2:19][CH2:18][NH:17][C@H:16]1[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[N:9]([CH3:27])[C:8](=[O:28])[CH2:7][CH2:6]2.[C:29]([NH:36][CH2:37][CH2:38][N:39]=[C:40]=[S:41])([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30]>C1C=CC=CC=1.C(OCC)C>[C:32]([O:31][C:29](=[O:30])[NH:36][CH2:37][CH2:38][NH:39][C:40]([N:17]1[CH2:18][CH2:19][CH2:20][CH:15]([NH:14][CH2:13][C:12]2[CH:11]=[C:10]3[C:5]([CH2:6][CH2:7][C:8](=[O:28])[N:9]3[CH3:27])=[CH:4][C:3]=2[O:2][CH3:1])[CH:16]1[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)=[S:41])([CH3:35])([CH3:33])[CH3:34]
Reactant: CC(C)(C)OC(=O)NCCN=C=S
Reactant: COc1cc2c(cc1CN[C@H]1CCCN[C@H]1c1ccccc1)N(C)C(=O)CC2
Solvent: CCOCC
Solvent: c1ccccc1
Product: COc1cc2c(cc1CNC1CCCN(C(=S)NCCNC(=O)OC(C)(C)C)C1c1ccccc1)N(C)C(=O)CC2
Yield: 69.5 %

Procedure:
6-Methoxy-1-methyl-7-[(2S,3S)-(2-phenyl-piperidin-3-ylamino)-methyl]-3,4-dihydro-1H-quinolin-2-one (750 mg, 1.98 mmol) and N-BOC-2-isothiocyanatoethylamine (400 mg, 1.98 mmol) were stirred in 20 mL of benzene at room temperature for 16 hours. The reaction was diluted with diethyl ether and washed 1× with water, dried over MgSO4, filtered, and concentrated. Silica gel chromatography using (6:1 ethyl acetate/hexane) gave 800 mg (70% yield) of [2-({3-[(6-Methoxy-1-methyl-2-oxo-1,2,3,4-tetrahydro-quinolin-7-ylmethyl)-amino]-2-phenyl-piperidine-1-carbothioyl}-amino)-ethyl]-carbamic acid tert-butyl ester. Rf=0.11 (6:1 ethyl acetate/hexane).
Reaction SMILES: [NH2:1][CH2:2][CH2:3][N:4]([CH3:12])[C:5](=[O:11])[O:6][C:7]([CH3:10])([CH3:9])[CH3:8].C[Al](C)C.C[O:18][C:19]([C:21]1[S:22][CH:23]=[CH:24][C:25]=1[NH:26][C:27]1[C:28]2[CH:35]=[CH:34][NH:33][C:29]=2[N:30]=[CH:31][N:32]=1)=O.O>C1(C)C=CC=CC=1.CO>[CH3:12][N:4]([CH2:3][CH2:2][NH:1][C:19]([C:21]1[S:22][CH:23]=[CH:24][C:25]=1[NH:26][C:27]1[C:28]2[CH:35]=[CH:34][NH:33][C:29]=2[N:30]=[CH:31][N:32]=1)=[O:18])[C:5](=[O:11])[O:6][C:7]([CH3:8])([CH3:9])[CH3:10]
Reactant: COC(=O)c1sccc1Nc1ncnc2[nH]ccc12
Reactant: CN(CCN)C(=O)OC(C)(C)C
Agent: C[Al](C)C
Solvent: Cc1ccccc1
Solvent: CO
Solvent: O
Product: CN(CCNC(=O)c1sccc1Nc1ncnc2[nH]ccc12)C(=O)OC(C)(C)C
Temperature: 105 °C
Reaction time: 2 h

Procedure:
To a solution of tert-butyl (2-aminoethyl)(methyl)carbamate (158 μl; 154 mg; 0.88 mmol) in anhydrous toluene (3 mL) placed in a sealed tube under nitrogen was added a solution of trimethylaluminum (354 μl; 2 M; 0.71 mmol) in toluene. The colorless solution was stirred at 25° C. for 1 h, before 3-(7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)-thiophene-2-carboxylic acid methyl ester (55 mg; 0.18 mmol) was added and the resulting yellow suspension was heated to 105° C. overnight. The reaction mixture was allowed to cool down before water (0.1 mL) was added. The resulting gray suspension was stirred at 25° C. for 2 h, diluted with methanol and purified by chromatography on a SP1 Biotage system, using hexane and ethyl acetate as eluents to afford crude tert-butyl methyl[2-({[3-(7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)-2-thienyl]carbonyl}amino)ethyl]carbamate as a white solid. The solid was suspended in methanol (1 mL) in a 5 mL flask with magnetic stir bar. To the white suspension was added hydrochloric acid (0.21 mL, 2.0N in diethyl ether, 0.42 mmol). The resulting solution was stirred at 25° C. overnight and the resulting precipitate was collected by filtration. The precipitate was purified using preparative HPLC to afford 3-(7H-Pyrrolo[2,3-d]pyrimidin-4-ylamino)-thiophene-2-carboxylic acid (2-methylamino-ethyl)-amide (1 mg, 2%) as a brown solid. 1H NMR (MeOH-d4) 8.55 (d, J=5.5 Hz, 1H), 8.40 (s, 1H), 7.66 (d, J=5.2 Hz, 1H), 7.29 (d, J=3.7 Hz, 1H), 6.61 (d, J=3.3 Hz, 1H), 3.73-3.67 (m, 2H), 3.34-3.28 (m, 2H), 2.75 (s, 3H); MS (m/z) 317 [M+H]+.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[C:6]([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[N:5]2.C1C(=O)N([Br:31])C(=O)C1.CC(N=NC(C#N)(C)C)(C#N)C>>[Br:31][CH2:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[C:6]([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[N:5]2
Reactant: O=C1CCC(=O)N1Br
Reactant: Cc1ccc2nc(-c3ccccc3)c(-c3ccccc3)nc2c1
Agent: CC(C)(C#N)N=NC(C)(C)C#N
Product: BrCc1ccc2nc(-c3ccccc3)c(-c3ccccc3)nc2c1

Procedure:
6-Methyl-2,3-diphenylquinoxaline (5.0 g, 16.9 mmol) was dissolved in dry, oxygen free benzene (50 ml). The solution was brought to reflux and a mixture of NBS (3.00 g, 16.9 mmol) and AIBN (0.1 g) added as a solid over a period of 30 minutes. The solution was then refluxed for 2 hrs, cooled, washed with water (3×100 ml), dried over MgSO4 and evaporated to leave a pale brown solid. This was recrystallised from hexane/toluene (1:1, 80 ml) to yield 6-bromomethyl-2,3-diphenylquinoxaline, 3.5 g, 56%. Traces of 6-methyl-2,3-diphenylquinoxaline were shown to be present by 1H NMR. A small sample was recrystallised from acetone for characterisation (m.pt. 146-148° C.). Found: C,; H,; N, %; C21H15N2Br requires C, 67.21; H, 4.03; N, 7.47%. 1H NMR (CDCl3 , 300 MHz) δ 8.16 (d, J 8.7 Hz, 1H, Hs of quinoxaline), 8.16 (d, J 2.2 Hz, 1H, Hs of quinoxaline), 7.78 (d of d, J 8.7 Hz, J 2.2 Hz, 1H, Hs of quinoxaline), 7.48-7.56 (m, 4H, phenyl ring), 7.30-7.40 (m, 6H, phenyl ring), 4.71 (s, 2H, CH2Br).
Reaction SMILES: [H-].C[C@H]1C[C@]23[C@@H]4CCCN2CCC[C@@H]3C(=O)C[C@@H]4C1.[N:20]1[CH:25]=[CH:24][CH:23]=[C:22]([CH:26]=[CH:27][CH2:28][C:29]([O:31]CC)=[O:30])[CH:21]=1>>[N:20]1[CH:25]=[CH:24][CH:23]=[C:22]([CH:26]=[CH:27][CH2:28][C:29]([OH:31])=[O:30])[CH:21]=1
Reactant: CCOC(=O)CC=Cc1cccnc1
Agent: C[C@@H]1C[C@H]2CC(=O)[C@H]3CCCN4CCC[C@H]2[C@]34C1
Agent: [H-]
Product: O=C(O)CC=Cc1cccnc1

Procedure:
The target compound 4-pyridin-3-yl-but-3-enoic acid (Compound 2035) was prepared by two steps starting from the commercial available 3-Pyridinecarboxaldehyde. Reaction of this aldehyde with ethyl acrylate and triphenylphosphine in a sealed tube for 4 hr at 140° C. gave ethyl 4-pyridin-3-yl-3-butenoate in a 55% yield. Kirby, Anthony J.; Walwyn, David R. Effective molarities for intramolecular hydride transfer. Reduction by 1,4-dihydropyridines of the neighboring α-ketoester group. Gazzetta Chimica Italiana (1987), 117(11), 667-80. This reaction is a self-priming Wittig reaction and the yield was not optimized. Gilbert Stork, R. A. Kretchmer, R. H. Schlessinger. The Stereospecific Total Synthesis of dl-Lycopodine. J. Am. Chem. Soc. (1968), 90, 1647. Hydrolysis of the ester using the routine condition and the subsequent purification with preparative HPLC afforded the target compound 2035 with almost quantitative yield.
Reaction SMILES: [CH:1](/[C:12]1[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=1)=[CH:2]/[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH3:11].C(=O)([O-])[O-].[K+].[K+].[Br:25][CH2:26][CH2:27]Br>C(C(C)=O)C(C)C>[Br:25][CH2:26][CH2:27][O:18][C:15]1[CH:14]=[CH:13][C:12](/[CH:1]=[CH:2]\[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH3:11])=[CH:17][CH:16]=1
Reactant: CCCCCCCCC/C=C\c1ccc(O)cc1
Reactant: BrCCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(=O)CC(C)C
Product: CCCCCCCCC/C=C\c1ccc(OCCBr)cc1
Yield: 40.8 %

Procedure:
4-[(Z)-1-Undecenyl]phenol, (2.30 g, 9.30 mmol) and anhydrous potassium carbonate, (1.93 g, 14.0 mmol) in methyl isobutyl ketone (100 ml) were stirred and treated with 1,2-dibromoethane, (5.27 g, 29 mmol). The mixture was refluxed for 24 h after which time a further aliquot of 1,2-dibromoethane, (5.27 g, 28 mmol) was added. The mixture was refluxed a further 24 h, then cooled and washed with water, (twice). The organic phase was dried, (MgSO4), and evaporated in vacuo to an oil. Purification by column chromatography on silica gel, eluting with n-hexane then dichloromethane gave 1.34 g (41%) of the title compound as a white crystalline solid mp 40°-1° C. νmax (mull) 1510, 1573 (weak) 1610 cm-1, δ (CDCl3) 0.86 (3H, distorted t, terminal CH3), 1.26 (14H, m, (CH2)7), 2.26 (2H, m, allylic CH2), 3.60 (2H, t, J 6 Hz, CH2Br), 4.26 (2H, t, J 6 Hz, OCH2) 5.56 (1H, d.t, Jd 12 Hz, Jt 7 Hz, =CH--alkyl), 6.32 (1H, d, J 12 Hz, ArCH=), 7.06 (4H, ABq, Δν 33 Hz, J 9 Hz, C6H4).
Reaction SMILES: [C:1]([C:4]1[CH:13]=[CH:12][C:7]([C:8]([O:10][CH3:11])=[O:9])=[CH:6][CH:5]=1)(=[S:3])[NH2:2].[CH3:14][C:15]1[CH:24]=[CH:23][C:18]([C:19](=O)[CH2:20]Br)=[CH:17][CH:16]=1>>[CH3:14][C:15]1[CH:24]=[CH:23][C:18]([C:19]2[N:2]=[C:1]([C:4]3[CH:13]=[CH:12][C:7]([C:8]([O:10][CH3:11])=[O:9])=[CH:6][CH:5]=3)[S:3][CH:20]=2)=[CH:17][CH:16]=1
Reactant: Cc1ccc(C(=O)CBr)cc1
Reactant: COC(=O)c1ccc(C(N)=S)cc1
Product: COC(=O)c1ccc(-c2nc(-c3ccc(C)cc3)cs2)cc1
Yield: 61 %

Procedure:
In the same manner as in Example 28, methyl 4-thiocarbamoylbenzoate was reacted with 4-methylphenacyl bromide to obtain methyl 4-[4-(4-methylphenyl)-2-thiazolyl]benzoate. The product was recrystallized from ethanol. Yield: 61%. Pale yellow prisms. Melting point: 185 to 187° C.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([O:11][CH2:12][C@H:13]2[CH:22]=[CH:21][C:20]3[C:15](=[C:16]([C:24]4[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][C:25]=4[Cl:31])[C:17]([F:23])=[CH:18][CH:19]=3)[O:14]2)(=[O:10])=[O:9])=[CH:4][CH:3]=1>C(O)C.C(OCC)(=O)C.[Pt](=O)=O>[CH3:1][C:2]1[CH:3]=[CH:4][C:5]([S:8]([O:11][CH2:12][C@H:13]2[CH2:22][CH2:21][C:20]3[C:15](=[C:16]([C:24]4[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][C:25]=4[Cl:31])[C:17]([F:23])=[CH:18][CH:19]=3)[O:14]2)(=[O:10])=[O:9])=[CH:6][CH:7]=1
Reactant: Cc1ccc(S(=O)(=O)OC[C@H]2C=Cc3ccc(F)c(-c4ccc(Cl)cc4Cl)c3O2)cc1
Agent: O=[Pt]=O
Solvent: CCO
Solvent: CCOC(C)=O
Product: Cc1ccc(S(=O)(=O)OC[C@H]2CCc3ccc(F)c(-c4ccc(Cl)cc4Cl)c3O2)cc1
Yield: 99.6 %

Procedure:
Treatment of ((2R)-8-(2,4-dichlorophenyl)-7-fluoro-2H-chromen-2-yl)methyl 4-methylbenzenesulfonate (0.35 g, 0.73 mmol) with platinum (IV) oxide (84% Pt, 0.14 g) in ethanol (20 mL) and ethyl acetate (5 mL) according to the procedure described for Example 69, Step 8 provided 0.35 g (100%) of ((2R)-8-(2.4-dichlorophenyl)-7-fluorochroman-2-yl)methyl 4-methylbenzenesulfonate as a light brown oil.
Reaction SMILES: [C:1]1([C:7]2[O:11][C:10](=[O:12])[C:9](=[CH:13][C:14]3[S:15][CH:16]=[CH:17][CH:18]=3)[CH:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CS(O)(=O)=O>C(O)(=O)C>[C:1]1([C:7]2[C:18]3[CH:17]=[CH:16][S:15][C:14]=3[CH:13]=[C:9]([C:10]([OH:11])=[O:12])[CH:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: O=C1OC(c2ccccc2)=CC1=Cc1cccs1
Agent: CS(=O)(=O)O
Solvent: CC(=O)O
Product: O=C(O)c1cc(-c2ccccc2)c2ccsc2c1
Temperature: 40 °C
Yield: 49.9 %

Procedure:
5-Phenyl-3-(2-thienylmethylene)-2-furanone (34.9 g), methanesulfonic acid (170 cc) and glacial acetic acid (170 cc) are heated for one hour at 120° C. The mixture is cooled to 40° C., poured onto crushed ice and extracted with methylene chloride. The organic phase is washed with water and extracted with a normal sodium hydroxide solution. The basic aqueous phase is washed with methylene chloride, acidified to pH 1 by adding an aqueous hydrochloric acid solution and extracted with methylene chloride. The precipitate formed is filtered, the organic phase is dried over magnesium sulfate and evaporated under reduced pressure. The evaporation residue and the precipitate are combined and chromatographed on silica gel using ethyl acetate as the eluent. 4-Phenylbenzo[b]thiophene-6-carboxylic acid (17.4 g), m.p. 222° C., is thereby isolated.