Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([C:8]([NH:10][CH2:11][C:12]2[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=2)=[O:9])[CH:3]=1.CC1(C)C(C)(C)OB(/[CH:28]=[CH:29]/[C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)O1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.O>[CH3:19][O:18][C:15]1[CH:16]=[CH:17][C:12]([CH2:11][NH:10][C:8](=[O:9])[C:4]2[CH:3]=[C:2](/[CH:28]=[CH:29]/[C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[CH:7]=[CH:6][N:5]=2)=[CH:13][CH:14]=1
Reactant: COc1ccc(CNC(=O)c2cc(Br)ccn2)cc1
Reactant: CC1(C)OB(/C=C/c2ccccc2)OC1(C)C
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: O
Solvent: C1COCCO1
Product: COc1ccc(CNC(=O)c2cc(/C=C/c3ccccc3)ccn2)cc1
Temperature: 95 °C
Reaction time: 12 h
Yield: 77.7 %

Procedure:
To a flask containing 4-bromo-N-(4-methoxybenzyl)picolinamide (0.3 g) in 1,4-dioxane (1.1 mL) was added (E)-4,4,5,5-tetramethyl-2-styryl-1,3,2-dioxaborolane (0.22 g), Pd(dppf)—chloroform adduct (0.04 g) and 2M aqueous cesium carbonate (1.9 mL). The mixture was stirred at about 95° C. for about 12 h. The reaction was diluted with water and washed three times with CH2Cl2. The organic solution was filtered over Celite®, and concentrated under reduced pressure yielding (E)-N-(4-methoxybenzyl)-4-styrylpicolinamide as a deep yellow oil (0.25 g, 80%). LC/MS (Table-1, Method f) Rt=2.03 min; MS m/z 345 (M+H)+. This intermediate was then dissolved in 4.3 mL of 1,4-dioxane and treated with 0.87 mL of water and sodium periodate (0.75 g). After stirring for approximately 30 min at RT, osmium tetroxide (0.30 mL of a 0.1 M solution in t-butanol) was added to the reaction which was then stirred for about an additional 4 h at RT. The layers were separated and the organic solution was dried over MgSO4, filtered, and concentrated under reduced pressure. The product was isolated by flash chromatography to give 4-formyl-N-(4-methoxybenzyl)picolinamide (0.25 g, 80%): LC/MS (Table 1, method-f) Rt=1.01 min; MS m/z 271 (M+H)+.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([OH:10])=[CH:6][CH:5]=1)([O-:3])=[O:2].[H-].[Na+].[CH3:13][O:14][CH2:15][CH2:16]Br>CN(C=O)C>[CH3:13][O:14][CH2:15][CH2:16][O:10][C:7]1[CH:8]=[CH:9][C:4]([N+:1]([O-:3])=[O:2])=[CH:5][CH:6]=1
Reactant: O=[N+]([O-])c1ccc(O)cc1
Reactant: COCCBr
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COCCOc1ccc([N+](=O)[O-])cc1
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 104.1 %

Procedure:
A stirred solution of 4-nitrophenol (Fluka) (0.511 g, 3.67 mmol) in DMF (10 mL) was treated with 60% sodium hydride (Aldrich) (0.170 g, 4.25 mmol) added in portions at 0° C. The yellow mixture was stirred at that temperature for 10 min, then 2-bromoethyl methyl ether (Aldrich) (0.380 mL, 4.04 mmol) was added dropwise at 0° C. The mixture was stirred at that temperature for 5 min, warmed up to rt and stirred for 3.5 h then at 70° C. overnight. The reaction mixture was poured into ice-water (100 mL). The aqueous phase was extracted with EtOAc (2×70 mL). The combined organic phases were dried over sodium sulfate, filtered and concentrated in vacuo to give 1-(2-methoxyethoxy)-4-nitrobenzene (0.753 g, 105% yield) as an off-white solid. 1H NMR (400 MHz, CDCl3) δ 8.16-8.25 (m, 2H); 6.95-7.03 (m, 2H); 4.17-4.26 (m, 2H); 3.73-3.84 (m, 2H); 3.46 (s, 3H). m/z (ESI, +ve ion) 198.1 (M+H)+.
Reaction SMILES: [C:1](OC(C1C=CN(C2C=CC(C3C=CC=CC=3)=CC=2)C=1)C(N1[C@@H](CC2C=CC=CC=2)COC1(C)C)=O)(=[O:3])[CH3:2].[CH2:39]([O:41][C:42](=[O:62])[CH:43]([C:45]1[O:49][C:48]([C:50]2[CH:55]=[CH:54][C:53]([C:56]3[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=3)=[CH:52][CH:51]=2)=[CH:47][CH:46]=1)[OH:44])[CH3:40]>>[CH2:39]([O:41][C:42](=[O:62])[CH:43]([O:44][C:1](=[O:3])[CH3:2])[C:45]1[O:49][C:48]([C:50]2[CH:55]=[CH:54][C:53]([C:56]3[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=3)=[CH:52][CH:51]=2)=[CH:47][CH:46]=1)[CH3:40]
Reactant: CCOC(=O)C(O)c1ccc(-c2ccc(-c3ccccc3)cc2)o1
Reactant: CC(=O)OC(C(=O)N1[C@@H](Cc2ccccc2)COC1(C)C)c1ccn(-c2ccc(-c3ccccc3)cc2)c1
Product: CCOC(=O)C(OC(C)=O)c1ccc(-c2ccc(-c3ccccc3)cc2)o1
Yield: 83 %

Procedure:
According to the procedure described in Example 13 for the preparation of 2-acetoxy-1-(4(S)-benzyl-2,2-dimethyl-oxazolidin-3-yl)-2-(biphenyl-4-yl-1H-pyrrol-3-yl)-ethanone, 2-(2-biphenyl-4-yl-furan-5-yl)-2-hydroxy-acetic acid ethyl ester was acylated to furnish in 83% yield 2-acetoxy-2-(2-biphenyl-4-yl-furan-5-yl)-acetic acid ethyl ester which was used without purification. Flash column chromatography with 0-20% EtOAc/hex as eluant gave an analytically pure pink solid, mp 136-140° C. 1H NMR: δ 7.74 (d, 2H, J=8.5 Hz), 7.63 (d, 4H, J=8.5 Hz), 7.46 (t, 2H, =7.4 Hz), 7.36 (t, 1H, J=7.2 Hz), 6.68 (d, 1H, J=3.7 Hz), 658 (d, 1H, J=3.3 Hz), 6.57 (s, 1H), 4.29 (q, 2H, J=7.0 Hz), 2.21 (s, 3H), 1.29 (t, 3H, J=7.2 Hz). Anal. Calculated for C22H20O5 : C, 72.51; H, 5.53. Found: C, 72.61; H, 5.63.
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6](B2OC(C)(C)C(C)(C)O2)[CH:5]=[CH:4][C:3]=1[C:17]1[N:18]=[CH:19][C:20]([NH2:23])=[N:21][CH:22]=1.Br[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[NH:31][S:32]([N:35]1[CH2:39][CH2:38][CH2:37][CH2:36]1)(=[O:34])=[O:33]>>[NH2:23][C:20]1[N:21]=[CH:22][C:17]([C:3]2[CH:4]=[CH:5][C:6]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=3[NH:31][S:32]([N:35]3[CH2:39][CH2:38][CH2:37][CH2:36]3)(=[O:34])=[O:33])=[CH:7][C:2]=2[F:1])=[N:18][CH:19]=1
Reactant: CC1(C)OB(c2ccc(-c3cnc(N)cn3)c(F)c2)OC1(C)C
Reactant: O=S(=O)(Nc1ccccc1Br)N1CCCC1
Product: Nc1cnc(-c2ccc(-c3ccccc3NS(=O)(=O)N3CCCC3)cc2F)cn1

Procedure:
The title compound was prepared in a manner similar to that described in Example 571 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrazin-2-amine and N-(2-bromophenyl)pyrrolidine-1-sulfonamide in Step B. MS (ESI): mass calcd. for C20H20FN5O2S, 413.13; m/z found, 414.2 [M+H]+. 1H NMR (500 MHz, CDCl3) δ 8.40 (dd, J=5.4, 1.4, 2H), 8.14 (m, 1H), 7.61 (dd, J=8.3, 1.1, 1H), 7.42-7.35 (m, 1H), 7.32 (dd, J=8.0, 1.7, 1H), 7.23 (dd, J=3.6, 1.6, 1H), 7.22-7.15 (m, 1H), 6.44 (s, 1H), 3.33-3.25 (m, 4H), 1.87 (dd, J=7.0, 0.9, 4H).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[O:8][CH:7]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[CH2:6][C:5]2=O.[CH3:19][C:20]([S:23]([NH2:26])(=O)=[O:24])([CH3:22])[CH3:21]>C1COCC1.[Cl-].[Na+].O>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[O:8][CH:7]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[CH2:6][C:5]2=[N:26][S:23]([C:20]([CH3:22])([CH3:21])[CH3:19])=[O:24]
Reactant: O=C1CC(c2ccccc2)Oc2ccc(Br)cc21
Reactant: CC(C)(C)S(N)(=O)=O
Agent: [Cl-]
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Product: CC(C)(C)S(=O)N=C1CC(c2ccccc2)Oc2ccc(Br)cc21
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 39 %

Procedure:
To a solution of 6-bromo-2-phenylchroman-4-one (2.010 g, 6.63 mmol) and 2-methyl-2-propane sulfonamide (804 mg, 6.63 mmol) in anhydrous THF (22 mL) is added Ti(OEt)4 (3.025 g, 2.80 mL, 13.22 mmol). The resulting mixture is heated to reflux for 20 h. Brine (10 mL) is added after the mixture is cooled to rt, and stirred vigorously for 10 min. The mixture is filtered through a pad of Celite, and washed with ethyl acetate (50 mL). The filtrate is washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated. The residue is purified through chromatography on silica gel to afford N-(6-bromo-2-phenylchroman-4-ylidene)-2-methylpropane-2-sulfinamide 1.05 g, 39%) as a light yellow solid. MS ESI +ve m/z 406 (M+H)+
Reaction SMILES: [NH2:1][C:2]1[C:7]([CH:8]=[O:9])=[C:6](Cl)[N:5]=[CH:4][N:3]=1.[F:11][C:12]1[CH:13]=[C:14]([CH:26]=[CH:27][CH:28]=1)[CH2:15][N:16]1[C:24]2[C:19](=[CH:20][C:21]([NH2:25])=[CH:22][CH:23]=2)[CH:18]=[N:17]1.C(N(C(C)C)CC)(C)C>CS(C)=O>[NH2:1][C:2]1[C:7]([CH:8]=[O:9])=[C:6]([NH:25][C:21]2[CH:20]=[C:19]3[C:24](=[CH:23][CH:22]=2)[N:16]([CH2:15][C:14]2[CH:26]=[CH:27][CH:28]=[C:12]([F:11])[CH:13]=2)[N:17]=[CH:18]3)[N:5]=[CH:4][N:3]=1
Reactant: Nc1ncnc(Cl)c1C=O
Reactant: Nc1ccc2c(cnn2Cc2cccc(F)c2)c1
Solvent: CS(C)=O
Solvent: CCN(C(C)C)C(C)C
Product: Nc1ncnc(Nc2ccc3c(cnn3Cc3cccc(F)c3)c2)c1C=O
Temperature: 100 °C
Reaction time: 2 h

Procedure:
To a mixture of 4-amino-6-chloro-pyrimidine-5-carbaldehyde (95.5 mg, 0.61 mmol) and 1-(3-fluoro-benzyl)-1H-indazol-5-ylamine (147 mg, 0.61 mmol) in DMSO (1.5 mL) was added diisopropylethylamine (DIEA, 79 mg, 0.61 mmol). The mixture was stirred at 100° C. for 2 h, cooled to room temperature, then partitioned between ethyl acetate and H2O. The combined ethyl acetate extracts were dried over Na2SO4 and evaporated to afford a yellow solid, which was used in the next step without further purification.
Reaction SMILES: [CH:1]1([C:7]([O:9][CH2:10][CH3:11])=[O:8])[CH2:6][CH2:5][CH:4]=[CH:3][CH2:2]1.ClC1C=CC=C(C(OO)=[O:20])C=1.C([O-])([O-])=O.[Na+].[Na+]>C(Cl)Cl>[CH:3]12[O:20][CH:4]1[CH2:5][CH2:6][CH:1]([C:7]([O:9][CH2:10][CH3:11])=[O:8])[CH2:2]2
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: CCOC(=O)C1CC=CCC1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: ClCCl
Product: CCOC(=O)C1CCC2OC2C1
Temperature: 25 °C
Reaction time: 2.5 h

Procedure:
To a solution of ethyl cyclohex-3-ene-1-carboxylate (14.0 g, 90 mmol) in CH2Cl2 (350 mL) was added meta-chloroperbenzoic acid (18.9 g, 110 mmol) at 0° C. The reaction mixture was stirred at room temperature for 2.5 hours. After cooling to 0° C., the reaction was neutralized with aqueous Na2CO3 solution. The organic layer was collected and washed with water and brine, then was dried over MgSO4 and concentrated in vacuo to a light oil (17.8 g), which was used in the next reaction with further purification.
Reaction SMILES: [CH3:1][S:2](Cl)(=[O:4])=[O:3].[C:6]([O:10][C:11]1[CH:12]=[C:13]([C@H:24]([OH:27])[CH2:25][OH:26])[C:14]2[S:18][C:17]([O:19][CH:20]([CH3:22])[CH3:21])=[N:16][C:15]=2[CH:23]=1)([CH3:9])([CH3:8])[CH3:7]>N1C=CC=CC=1>[C:6]([O:10][C:11]1[CH:12]=[C:13]([C@H:24]([OH:27])[CH2:25][O:26][S:2]([CH3:1])(=[O:4])=[O:3])[C:14]2[S:18][C:17]([O:19][CH:20]([CH3:21])[CH3:22])=[N:16][C:15]=2[CH:23]=1)([CH3:7])([CH3:8])[CH3:9]
Reactant: CC(C)Oc1nc2cc(OC(C)(C)C)cc([C@H](O)CO)c2s1
Reactant: CS(=O)(=O)Cl
Solvent: c1ccncc1
Product: CC(C)Oc1nc2cc(OC(C)(C)C)cc([C@H](O)COS(C)(=O)=O)c2s1
Temperature: 0 °C
Reaction time: 3 h

Procedure:
Methane sulfonylchloride (112 mg) is added to (S)-1-(5-tert-Butoxy-2-isopropoxy-benzothiazol-7-yl)-ethane-1,2-diol (289 mg) in pyridine (2 ml) at 0° C. The reaction mixture is then stirred at 0° C. for 3 hours. The solvent is removed in vacuo, The resulting residue is partitioned between HCl(aq) (2M) and ether. The organics is washed with water (2×), brine (1×), dried over MgSO4, filtered and the solvent removed in vacuo to give the title compound. 1H nmr (CDCl3, 400 MHz); 7.20 (d, 1H), 6.80 (d, 1H), 5.30 (sept, 1H), 5.10 (t, 1H), 4.30 (d, 2H), 3.00 (s, 3H), 1.40 (d, 6H), 1.30 (s, 9H).
Reaction SMILES: [Cl:1][C:2]1[C:7]([Cl:8])=[CH:6][CH:5]=[CH:4][C:3]=1[S:9]([NH:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]2[CH:24]=[N:23][C:22]([C:25]#[N:26])=[C:21](Cl)[N:20]=2)=[CH:15][CH:14]=1)(=[O:11])=[O:10].[NH2:28][NH2:29]>CC(O)C.O>[NH2:26][C:25]1[C:22]2[C:21](=[N:20][C:19]([C:16]3[CH:15]=[CH:14][C:13]([NH:12][S:9]([C:3]4[CH:4]=[CH:5][CH:6]=[C:7]([Cl:8])[C:2]=4[Cl:1])(=[O:10])=[O:11])=[CH:18][CH:17]=3)=[CH:24][N:23]=2)[NH:29][N:28]=1
Reactant: NN
Reactant: N#Cc1ncc(-c2ccc(NS(=O)(=O)c3cccc(Cl)c3Cl)cc2)nc1Cl
Solvent: O
Solvent: CC(C)O
Product: Nc1n[nH]c2nc(-c3ccc(NS(=O)(=O)c4cccc(Cl)c4Cl)cc3)cnc12
Temperature: 120 °C

Procedure:
2,3-Dichloro-N-[4-(6-chloro-5-cyano-pyrazin-2yl)-phenyl]-benzenesulfonamide (1.0 g) was suspended in a mixture of 5 ml iPrOH and 5 ml 35% hydrazine in water at RT and heated to 120° C. by microwave irradiation for 20 min under stirring in a sealed vessel. The reaction mixture was left to cool to RT. The precipitate was filtered off and washed with water to give the title compound as a yellow solid after drying under vacuum. Yield: 536 mg (54%).
Reaction SMILES: ClC(Cl)=[C:3]([C:11]1[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][CH:12]=1)[C:4]1[CH:9]=[CH:8][C:7]([Cl:10])=[CH:6][CH:5]=1.[N+]([O-])(O)=[O:20]>O>[Cl:10][C:7]1[CH:8]=[CH:9][C:4]([C:3]([C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][CH:12]=2)=[O:20])=[CH:5][CH:6]=1
Reactant: ClC(Cl)=C(c1ccc(Cl)cc1)c1ccc(Cl)cc1
Reactant: O=[N+]([O-])O
Solvent: O
Product: O=C(c1ccc(Cl)cc1)c1ccc(Cl)cc1
Temperature: 20 °C

Procedure:
A 200 ml flask equipped with a stirrer was charged with 3.3 g of 1,1-dichloro-2,2-bis(4-chlorophenyl)ethylene and then with 50 ml of an aqueous nitric acid solution having a specific gravity of 1.52. The weight ratio of the reaction material to the aqueous solution of nitric acid was 0.043. While vigorously stirring the resulting mixture at room temperature of about 20° C. in a nitrogen atmosphere, they were reacted for 1 hour. The reaction mixture was thereafter added with water, followed by extraction with dichloromethane. After sufficient washing of the dichloromethane layer with water, the extract was analyzed by gas chromatography. As a result, it was found that 1,1-dichloro-2,2-bis(4-chlorophenyl)ethylene was converted in its entirety to 4,4'-dichloro-3,3'-dinitrobenzophenone, but no 4,4'-dichlorobenzophenone was formed at all.
Reaction SMILES: C(=O)([O-])N.[CH:5]12[O:12][CH:9]([CH2:10][CH2:11]1)[CH2:8][N:7]([C:13]1[N:18]=[C:17]([C:19]3[CH:24]=[CH:23][C:22]([NH:25][C:26](NCC)=[O:27])=[CH:21][CH:20]=3)[N:16]=[C:15]3[N:31]([CH:34]4CCN(C(OCC)=O)C[CH2:35]4)[N:32]=[CH:33][C:14]=13)[CH2:6]2.[CH2:45]([OH:49])[CH:46]([OH:48])[CH3:47]>>[CH:9]12[O:12][CH:5]([CH2:11][CH2:10]1)[CH2:6][N:7]([C:13]1[N:18]=[C:17]([C:19]3[CH:24]=[CH:23][C:22]([NH:25][C:26](=[O:27])[O:49][CH2:45][CH:46]([OH:48])[CH3:47])=[CH:21][CH:20]=3)[N:16]=[C:15]3[N:31]([CH2:34][CH3:35])[N:32]=[CH:33][C:14]=13)[CH2:8]2
Reactant: CC(O)CO
Reactant: CCNC(=O)Nc1ccc(-c2nc(N3CC4CCC(C3)O4)c3cnn(C4CCN(C(=O)OCC)CC4)c3n2)cc1
Agent: NC(=O)[O-]
Product: CCn1ncc2c(N3CC4CCC(C3)O4)nc(-c3ccc(NC(=O)OCC(C)O)cc3)nc21

Procedure:
A carbamate formation procedure similar to that used for the synthesis of ethyl 4-(4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-6-(4-(3-ethylureido)phenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidine-1-carboxylate is used, utilizing 1,2-propanediol as the alcohol component. (24%, MS=453.2 (M+H))
Reaction SMILES: [NH2:1][C:2]1[C:3]([C:16]([NH:18][C@H:19]2[CH2:24][CH2:23][CH2:22][N:21](C(OC(C)(C)C)=O)[CH2:20]2)=[O:17])=[N:4][C:5]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([CH2:14][NH2:15])[CH:9]=2)=[CH:6][N:7]=1.[F:32][C:33]1[CH:41]=[CH:40][C:36]([C:37](O)=[O:38])=[CH:35][CH:34]=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C>CN(C=O)C.O>[NH2:1][C:2]1[C:3]([C:16]([NH:18][C@H:19]2[CH2:24][CH2:23][CH2:22][NH:21][CH2:20]2)=[O:17])=[N:4][C:5]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([CH2:14][NH:15][C:37]([C:36]3[CH:40]=[CH:41][C:33]([F:32])=[CH:34][CH:35]=3)=[O:38])[CH:9]=2)=[CH:6][N:7]=1
Reactant: CC(C)(C)OC(=O)N1CCC[C@H](NC(=O)c2nc(-c3cccc(CN)c3)cnc2N)C1
Reactant: O=C(O)c1ccc(F)cc1
Agent: CCN=C=NCCCN(C)C
Agent: On1nnc2ccccc21
Solvent: O
Solvent: CN(C)C=O
Product: Nc1ncc(-c2cccc(CNC(=O)c3ccc(F)cc3)c2)nc1C(=O)N[C@H]1CCCNC1
Temperature: 25 °C
Reaction time: 8 h
Yield: 46.6 %

Procedure:
1,1-dimethylethyl (3S)-3-[({3-amino-6-[3-(amino-methyl)phenyl]pyrazin-2-yl}carbonyl)amino]piperidine-1-carboxylate (150.0 mg, 0.35 mmol) and 4-fluorobenzoic acid (50.0 mg, 0.36 mmol) was dissolved in DMF (5 mL) followed by the addition of HOBT (95.5 mg, 0.70 mmol) and EDCI (135.4 mg, 0.70 mmol). It was stirred at room temperature overnight. The reaction mixture was poured into water (20 mL), and extracted with ethyl acetate (2×30 mL) then dried over anhydrous sodium sulfate and filteration, concentration and purified by column chromatography (50% Ethylacetae/hexanes) and subsequently it was treated with 4.0 M HCl in dioxane (20 mL) to give compound 3-Amino-6-[3-({[(4-fluorophenyl)carbonyl]amino}methyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide: 70.0 mg (46.6% yield). 1H NMR (400 MHz, d4-MeOH): δ 8.62 (s, 1H), 8.16 (s, 1H), 7.98 (m, 3H), 7.48 (m, 2H), 7.20 (m, 3H), 4.67(s, 2H), 4.38 (m, 1H), 3.45 (m, 1H), 3.38 (m, 1H), 3.18 (m, 1H), 3.00 (m, 1H), 2.18 (m, 2H), 1.80 (m, 2H); MS (EI) for C24H25N6O2F: 449.32 (MH+).
Reaction SMILES: [OH-].[K+].[F:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[C:15]([C:16]3[CH:21]=[CH:20][N:19]=[CH:18][CH:17]=3)=[C:14]([C:22]3[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=3)[N:13]=[C:12]3[NH:29][N:30]=[C:31]([C:32]#[N:33])[C:11]=23)=[CH:6][CH:5]=1.O.CC[O:37]C(C)=O>CC(O)(C)C>[F:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[C:15]([C:16]3[CH:21]=[CH:20][N:19]=[CH:18][CH:17]=3)=[C:14]([C:22]3[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=3)[N:13]=[C:12]3[NH:29][N:30]=[C:31]([C:32]([NH2:33])=[O:37])[C:11]=23)=[CH:6][CH:5]=1
Reactant: CCOC(C)=O
Reactant: N#Cc1n[nH]c2nc(-c3ccc(F)cc3)c(-c3ccncc3)c(-c3ccc(F)cc3)c12
Agent: [K+]
Agent: [OH-]
Solvent: CC(C)(C)O
Solvent: O
Product: NC(=O)c1n[nH]c2nc(-c3ccc(F)cc3)c(-c3ccncc3)c(-c3ccc(F)cc3)c12
Yield: 28 %

Procedure:
A solution of KOH (0.07 g, 1.3 mmol) in tBuOH (2.5 mL) was added under argon atmosphere to 4,6-bis(4-fluorophenyl)-5-(4-pyridyl)-1H-pyrazolo[3,4-b]pyridine-3-carbonitrile (0.05 g, 0.1 mmol, obtained in example 65) and heated to reflux overnight. Water and EtOAc were added and the phases were separated. The aqueous phase was extracted with EtOAc. The combined organic phases were dried over Na2SO4 and concentrated to dryness. The crude product obtained was purified by chromatography on silica gel using hexane-EtOAc mixtures of increasing polarity as eluent, to afford 15 mg of the title compound in solid form (yield: 28%)
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([C:10]2[O:11][C:12]3[C:17]([C:18](=[O:20])[CH:19]=2)=[CH:16][CH:15]=[CH:14][CH:13]=3)[CH:5]=[CH:6][C:7]=1[O:8]C.CC(O)=O>O>[F:1][C:2]1[CH:3]=[C:4]([C:10]2[O:11][C:12]3[C:17]([C:18](=[O:20])[CH:19]=2)=[CH:16][CH:15]=[CH:14][CH:13]=3)[CH:5]=[CH:6][C:7]=1[OH:8]
Reactant: COc1ccc(-c2cc(=O)c3ccccc3o2)cc1F
Solvent: O
Solvent: CC(=O)O
Product: O=c1cc(-c2ccc(O)c(F)c2)oc2ccccc12
Temperature: 110 °C
Reaction time: 4 h
Yield: 72.5 %

Procedure:
To a solution of 2′-hydroxyacetophenone (1.36 g, 10 mmol) in 20 mL anhydrous pyridine was added 3-fluoro-4-methoxybenzoyl chloride (1.89 g, 10 mmol) and the reaction mixture was stirred at rt for 15 h under a nitrogen atmosphere. The reaction mixture was poured into 200 mL of 2 N HCl. The formed solid was isolated by filtration, washed with water and dried under vacuum to give a white solid (2.76 g, 95.7%). The compound (2.68 g, 9.3 mmol) was dissolved in 10 mL anhydrous pyridine. Powdered potassium hydroxide (1.57 g, 27.9 mmol) was added and the reaction mixture was stirred at rt overnight under nitrogen. Water (100 mL) was added, the solid was isolated by filtration and washed with water to give a yellow solid (1.83 g, 68%). The compound (1.78 g, 6.17 mmol) was suspended in 15 mL glacial AcOH. Five drops of conc. HCl was added and the reaction mixture was stirred at 110° C. for 2 h, then cooled to rt. Water (100 mL) was added. The formed solid was separated by filtration, washed with water and dried under vacuum to give 2-(3-fluoro-4-methoxyphenyl)chromen-4-one as a white solid (1.62 g, 97%). 2-(3-Fluoro-4-methoxyphenyl)chromen-4-one (1.6 g, 5.92 mmol) was suspended in 40 mL of Hi. Glacial AcOH (15 mL) was added and the reaction mixture was stirred at 110° C. for 4 h, then cooled to rt. Water (200 mL) was added, and the solid was isolated by filtration, washed with water and dried under vacuum. The crude compound was washed with 1:1 dichloromethane and methanol (15 mL) to give 1.1 g of 2-(3-fluoro-4-hydroxyphenyl)chromen-4-one (72%) as a pale yellow solid. MS (ES) m/z: 257.91 (M+1), 256.88 (M); Mp. 275-276° C.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH:14]=[O:15])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:16][Mg]Br.O>O1CCCC1>[C:1]([O:5][C:6]([NH:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH:14]([OH:15])[CH3:16])=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: C[Mg]Br
Reactant: CC(C)(C)OC(=O)NCCCCCC=O
Solvent: C1CCOC1
Solvent: O
Product: CC(O)CCCCCNC(=O)OC(C)(C)C
Reaction time: 2 h

Procedure:
Under argon atmosphere, a solution of 650 mg of 6-tert-butoxycarbonylaminohexanal in 10 mL of anhydrous tetrahydrofuran was cooled to −78° C., and treated dropwise with 6.8 mL of methylmagnesium bromide (a 1.0 M solution in tetrahydrofuran). After 2 hours, the reaction solution was combined with water, extracted with ethyl acetate, and dried. After concentrating, the residue was purified by column chromatography on silica gel (n-hexane:ethyl acetate=2:1) to obtain 280 mg of the desirable compound.
Reaction SMILES: C(Cl)(=O)CCCCCCCCCCCCC.[C:17]([NH:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH3:46])(=O)[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH3:30].C(N)CCCCCCCCCCCCC.C1CCN2C(=NCCC2)CC1>C(Cl)Cl>[CH2:33]([NH:32][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH3:30])[CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH3:46]
Reactant: CCCCCCCCCCCCCCNC(=O)CCCCCCCCCCCCC
Agent: CCCCCCCCCCCCCC(=O)Cl
Agent: CCCCCCCCCCCCCCN
Solvent: C1CCC2=NCCCN2CC1
Solvent: ClCCl
Product: CCCCCCCCCCCCCCNCCCCCCCCCCCCCC
Temperature: 25 °C
Reaction time: 4 h
Yield: 83 %

Procedure:
N-myristyl myristamide Myristoyl chloride (2.5 g; 10 mmole) was added to a room temperature methylene chloride solution of n-tetradecylamine (2.1 g; 10 mmole, TCI chemicals) and DBU (2.3 g; 15 mmole). The resulting mixture was stirred at room temperature for 4 hours, diluted with CH2Cl2, washed with brine solution, dried, and purified by column chromatography on silica gel, to give 3.40 g, 80.9% of product. 1H NMR (CDCl3): δ 5.38 (6s, 1H), 3.24 (q, 2H), 2.16 (t, 2H, J=7.8 Hz), 1.58-1.66 m, 2H), 1.40-1.57 (m, 2H), 1.20-1.40 (m, 42H), 0.89 (t, 6H).
Reaction SMILES: [CH2:1]([C:4]1[NH:5][C:6]2[C:11]([CH:12]=1)=[CH:10][CH:9]=[C:8]([C:13]([O:15][CH3:16])=[O:14])[CH:7]=2)[CH2:2][CH3:3].[Cl:17][C:18]1[CH:25]=[CH:24][CH:23]=[CH:22][C:19]=1[CH2:20]Br>>[Cl:17][C:18]1[CH:25]=[CH:24][CH:23]=[CH:22][C:19]=1[CH2:20][N:5]1[C:6]2[C:11](=[CH:10][CH:9]=[C:8]([C:13]([O:15][CH3:16])=[O:14])[CH:7]=2)[CH:12]=[C:4]1[CH2:1][CH2:2][CH3:3]
Reactant: CCCc1cc2ccc(C(=O)OC)cc2[nH]1
Reactant: Clc1ccccc1CBr
Product: CCCc1cc2ccc(C(=O)OC)cc2n1Cc1ccccc1Cl
Yield: 72.6 %

Procedure:
Methyl 1-(2-chlorobenzyl)-2-propylindole-6-carboxylate (400 mg) was prepared from methyl 2-propylindole-6-carboxylate (350 mg) and 2-chlorobenzyl bromide (364 mg) in a similar manner to that of Example 1.
Reaction SMILES: Cl[CH2:2][C:3]1[N:8]=[C:7]([NH2:9])[CH:6]=[CH:5][N:4]=1.[NH:10]1[CH2:15][CH2:14][O:13][CH2:12][CH2:11]1.C(N(CC)CC)C>C(O)C>[O:13]1[CH2:14][CH2:15][N:10]([CH2:2][C:3]2[N:8]=[C:7]([NH2:9])[CH:6]=[CH:5][N:4]=2)[CH2:11][CH2:12]1
Reactant: Nc1ccnc(CCl)n1
Reactant: C1COCCN1
Solvent: CCO
Solvent: CCN(CC)CC
Product: Nc1ccnc(CN2CCOCC2)n1
Reaction time: 0.5 h
Yield: 61.6 %

Procedure:
A solution of 2-(chloromethyl)pyrimidin-4-amine 126 (30.0 g, 209 mmol), morpholine 63 (23.7 g, 272 mmol) and triethylamine (42.3 g, 418 mmol) in anhydrous ethanol (250 mL) was heated at reflux for 16 h. The solvent was removed in vacuo and methanol (400 mL), H2O (100 mL) and sodium bicarbonate (25.0 g) were added. Stirring was continued for 30 min. The mixture was concentrated and purified by flash chromatography (dichloromethane: methanol: triethylamine=100:8:0.5) to give 127 (25.0 g, 62% yield).