Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]([F:22])([F:21])[O:3][C:4]1[CH:5]=[C:6]([C:10]2[CH:11]=[CH:12][C:13]3[N:14]=[CH:15][N:16]=[C:17](O)[C:18]=3[N:19]=2)[CH:7]=[CH:8][CH:9]=1.O=S(Cl)[Cl:25]>>[Cl:25][C:17]1[C:18]2[N:19]=[C:10]([C:6]3[CH:7]=[CH:8][CH:9]=[C:4]([O:3][C:2]([F:22])([F:21])[F:1])[CH:5]=3)[CH:11]=[CH:12][C:13]=2[N:14]=[CH:15][N:16]=1
Reactant: O=S(Cl)Cl
Reactant: Oc1ncnc2ccc(-c3cccc(OC(F)(F)F)c3)nc12
Product: FC(F)(F)Oc1cccc(-c2ccc3ncnc(Cl)c3n2)c1

Procedure:
A solution of 6-(3-(trifluoromethoxy)phenyl)pyrido[3,2-d]pyrimidin-4-ol (1.2 g, 3.9 mmol) in SOCl2 (10 mL) was refluxed for 2 hours. The reaction was concentrated under reduce pressure, and the residue was chased with toluene (10 mL) to obtain 4-chloro-6-(3-(trifluoromethoxy)phenyl)pyrido[3,2-d]pyrimidine as a brown solid. Used as is without further purification.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][N:11]([CH:14]([C:17]3[CH:22]=[CH:21][C:20]([NH2:23])=[CH:19][CH:18]=3)[CH2:15][CH3:16])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.Cl[C:25]1[C:34]2[C:29](=[CH:30][C:31]([C:35]([F:38])([F:37])[F:36])=[CH:32][CH:33]=2)[N:28]=[CH:27][CH:26]=1>>[F:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[CH2:9][CH2:10][N:11]([CH:14]([C:17]3[CH:18]=[CH:19][C:20]([NH:23][C:25]4[C:34]5[C:29](=[CH:30][C:31]([C:35]([F:38])([F:36])[F:37])=[CH:32][CH:33]=5)[N:28]=[CH:27][CH:26]=4)=[CH:21][CH:22]=3)[CH2:15][CH3:16])[CH2:12][CH2:13]2)=[CH:6][CH:7]=1
Reactant: CCC(c1ccc(N)cc1)N1CCN(c2ccc(F)cc2)CC1
Reactant: FC(F)(F)c1ccc2c(Cl)ccnc2c1
Product: CCC(c1ccc(Nc2ccnc3cc(C(F)(F)F)ccc23)cc1)N1CCN(c2ccc(F)cc2)CC1

Procedure:
In the manner given in Example 1C, 1-(p-fluorophenyl)-4-[1-(4-aminophenyl)propyl]piperazine and 4-chloro-7-(trifluoromethyl)quinoline are reacted together at reflux to give 4-[[4-[1-[4-(p-fluorophenyl)-1-piperazinyl]propyl]phenyl]amino]-7-(trifluoromethyl)quinoline.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[CH2:11][N:12]1[C:20]([C:21]2[N:25]([CH3:26])[CH:24]=[C:23]([C:27](O)=[O:28])[CH:22]=2)=[C:19]2[C:14]([N:15]([CH2:33][CH:34]([CH3:36])[CH3:35])[C:16](=[O:32])[N:17]([CH3:31])[C:18]2=[O:30])=[N:13]1.CN.[C:39](P(=O)(OCC)OCC)#[N:40]>>[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[CH2:11][N:12]1[C:20]([C:21]2[N:25]([CH3:26])[CH:24]=[C:23]([C:27]([NH:40][CH3:39])=[O:28])[CH:22]=2)=[C:19]2[C:14]([N:15]([CH2:33][CH:34]([CH3:35])[CH3:36])[C:16](=[O:32])[N:17]([CH3:31])[C:18]2=[O:30])=[N:13]1
Reactant: CC(C)Cn1c(=O)n(C)c(=O)c2c(-c3cc(C(=O)O)cn3C)n(Cc3c[nH]c4ccc(Cl)cc34)nc21
Reactant: CCOP(=O)(C#N)OCC
Agent: CN
Product: CNC(=O)c1cc(-c2c3c(=O)n(C)c(=O)n(CC(C)C)c3nn2Cc2c[nH]c3ccc(Cl)cc23)n(C)c1

Procedure:
This compound was synthesized by the reaction of 5-{2-[(5-chloro-1H-indol-3-yl)methyl]-7-isobutyl-5-methyl-4,6-dioxo-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-d]pyrimidin-3-yl}-1-methyl-1H-pyrrole-3-carboxylic acid and methylamine using diethyl cyanophosphonate as a coupling reagent. Mass: 522.19 (M+H).
Reaction SMILES: [NH2:1][C:2]1[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][C:3]=1[CH:4]([OH:20])[C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([CH2:11][NH:12][C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH:6]=1.[CH:26](=O)[CH:27]=[CH:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1.C(O)(=O)C.[BH4-].C([Na])#N>CO>[C:16]([O:15][C:13]([NH:12][CH2:11][C:7]1[CH:6]=[C:5]([CH:4]([OH:20])[C:3]2[CH:21]=[C:22]([Cl:25])[CH:23]=[CH:24][C:2]=2[NH:1][CH2:26][CH:27]=[CH:28][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH:10]=[CH:9][CH:8]=1)=[O:14])([CH3:18])([CH3:19])[CH3:17]
Reactant: O=CC=Cc1ccccc1
Reactant: CC(C)(C)OC(=O)NCc1cccc(C(O)c2cc(Cl)ccc2N)c1
Agent: N#C[Na]
Agent: [BH4-]
Solvent: CO
Solvent: CC(=O)O
Product: CC(C)(C)OC(=O)NCc1cccc(C(O)c2cc(Cl)ccc2NCC=Cc2ccccc2)c1
Temperature: 25 °C

Procedure:
In methanol (15 ml) were dissolved 2-amino-5-chloro-α-(3-tert-butoxycarbonylaminomethylphenyl)benzyl alcohol (0.6 g) produced in Example (1) and cinnamaldehyde.(0.5 g). To the solution was added acetic acid (0.11 g). To the mixture was added, while stirring at room temperature, cyano sodium borohydride (0.12 g). The reaction mixture was stirred for 40 minutes at 60° C., which was concentrated. The concentrate was subjected to extraction by the addition of water (30 ml) and ethyl acetate (50 ml). The organic layer was washed with water and dried over anhydrous sodium sulfate. The solvent was distilled off, and the residue was purified by means of a silica gel column chromatography to give a-(3-tert-butoxycarbonylaminomethylphenyl)-5-chloro-2-[(3-phenyl)-2-propenyl]amino-benzyl alcohol (0.8 g) as a colorless oily product.
Reaction SMILES: [N+:1]([C:4]1[CH:12]=[CH:11][C:7]([C:8](Cl)=[O:9])=[CH:6][CH:5]=1)([O-:3])=[O:2].[CH2:13]([O:20][C:21](=[O:45])[CH2:22][C@:23]1([C:35]([O:37][CH2:38][C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)=[O:36])[O:27][N:26]=[C:25]([C:28]2[CH:33]=[CH:32][CH:31]=[C:30]([OH:34])[CH:29]=2)[CH2:24]1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.C(OCC)(=O)C.Cl>N1C=CC=CC=1.O>[CH2:13]([O:20][C:21](=[O:45])[CH2:22][C@:23]1([C:35]([O:37][CH2:38][C:39]2[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=2)=[O:36])[O:27][N:26]=[C:25]([C:28]2[CH:33]=[CH:32][CH:31]=[C:30]([O:34][C:8](=[O:9])[C:7]3[CH:6]=[CH:5][C:4]([N+:1]([O-:3])=[O:2])=[CH:12][CH:11]=3)[CH:29]=2)[CH2:24]1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1
Reactant: O=C(C[C@@]1(C(=O)OCc2ccccc2)CC(c2cccc(O)c2)=NO1)OCc1ccccc1
Reactant: O=C(Cl)c1ccc([N+](=O)[O-])cc1
Agent: Cl
Solvent: c1ccncc1
Solvent: CCOC(C)=O
Solvent: O
Product: O=C(C[C@@]1(C(=O)OCc2ccccc2)CC(c2cccc(OC(=O)c3ccc([N+](=O)[O-])cc3)c2)=NO1)OCc1ccccc1
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 98.1 %

Procedure:
4-Nitrobenzoyl chloride (105 g) was added in small portions to a solution of benzyl (5R)-5-(2-(benzyloxy)-2-oxoethyl)-3-(3-hydroxyphenyl)-4,5-dihydro-1,2-oxazole-5-carboxylate (126 g) in pyridine (380 mL) at 20 C. The obtained mixture was stirred at room temperature for 1.5 hours. To the reaction mixture, ethyl acetate (650 mL) and 1 M hydrochloric acid (1300 mL) were added at 0 C, and then, ethyl acetate (1300 mL) and water (260 mL) were added. The organic layer was separated, and the aqueous layer was subjected to extraction with ethyl acetate (1300 mL). Combined organic layers were washed with diluted aqueous ammonia ((28% aqueous ammonia (26 mL)/water (1300 mL))×2), 1 M hydrochloric acid (1300 mL×2), and brine (1300 mL) and dried over anhydrous sodium sulfate, and then, the solvent was distilled off under reduced pressure. The residue was washed with diisopropyl ether (1500 mL) to obtain the title compound (165 g).
Reaction SMILES: [CH:1]1([N:6]2[CH2:12][CH:11]([CH2:13][CH3:14])[C:10](=[O:15])[N:9]([CH2:16][CH3:17])[C:8]3[CH:18]=[N:19][C:20]([NH:22][C:23]4[CH:31]=[CH:30][C:26]([C:27]([OH:29])=O)=[CH:25][C:24]=4[O:32][CH3:33])=[N:21][C:7]2=3)[CH2:5][CH2:4][CH2:3][CH2:2]1.F[P-](F)(F)(F)(F)F.CN(C(N(C)C)=[N+]1C2C(=NC=CC=2)[N+]([O-])=N1)C.C(N(C(C)C)C(C)C)C.[NH2:67][CH:68]1[CH2:73][CH2:72][N:71]([CH3:74])[CH2:70][CH2:69]1>O.C(=O)(O)[O-].[Na+].CN(C)C=O>[CH:1]1([N:6]2[CH2:12][CH:11]([CH2:13][CH3:14])[C:10](=[O:15])[N:9]([CH2:16][CH3:17])[C:8]3[CH:18]=[N:19][C:20]([NH:22][C:23]4[CH:31]=[CH:30][C:26]([C:27]([NH:67][CH:68]5[CH2:73][CH2:72][N:71]([CH3:74])[CH2:70][CH2:69]5)=[O:29])=[CH:25][C:24]=4[O:32][CH3:33])=[N:21][C:7]2=3)[CH2:2][CH2:3][CH2:4][CH2:5]1
Reactant: CN1CCC(N)CC1
Reactant: CCC1CN(C2CCCC2)c2nc(Nc3ccc(C(=O)O)cc3OC)ncc2N(CC)C1=O
Agent: CN(C)C(N(C)C)=[N+]1N=[N+]([O-])c2ncccc21
Agent: F[P-](F)(F)(F)(F)F
Agent: O=C([O-])O
Solvent: O
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: CCC1CN(C2CCCC2)c2nc(Nc3ccc(C(=O)NC4CCN(C)CC4)cc3OC)ncc2N(CC)C1=O
Reaction time: 0.08 h
Yield: 86.4 %

Procedure:
A mixture of 0.037 g (0.00008 mole) of (rac)-4-(9-cyclopentyl-7-ethyl-5-ethyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-yl amino)-3-methoxy-benzoic acid (I-14), 0.037 g (0.00012 mole) of 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium-3-oxide hexafluorophosphate, 0.042 mL (0.00024 mole) of ethyldiisopropyl amine and 1 mL of dimethylformamide was stirred for 5 minutes and then 0.014 g (0.00012 mole) of 4-amino-1-methyl-piperidine was added. The mixture was stirred for 3 hours, then diluted with 10 mL of water plus 2 mL of saturated sodium bicarbonate and then extracted 3 times with 10 mL of ethyl acetate. The combined extracts were washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by reverse phase silica gel chromatography, eluting with an acetonitrile-water gradient (20:80-100:0) to give 0.038 g of (rac)-4-(9-cyclopentyl-5,7-diethyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-N-(1-methyl-piperidin-4-yl)-benzamide (I-15) as a white solid.
Reaction SMILES: [CH2:1]=[CH:2][CH:3]=[CH2:4].[H-].[CH2:6]([Al+]CC(C)C)C(C)C.[Nd].C(Br)C=C>[Nd].CCCCCC>[CH2:1]=[CH:2][C:3](=[CH2:6])[CH3:4].[CH2:1]=[CH:2][CH:3]=[CH2:4]
Reactant: CC(C)C[Al+]CC(C)C
Agent: C=CC=C
Agent: [H-]
Agent: [Nd]
Solvent: C=CCBr
Solvent: CCCCCC
Product: C=CC(=C)C
Temperature: 20 °C
Yield: 87 %

Procedure:
In this experiment, an isoprene-butadiene copolymer rubber was prepared using an alcohol modified neodymium catalyst system. In this procedure, a one gallon (3.78 liter) reactor was charged with 1,214 grams of hexane containing 81.3 grams of butadiene and 558.43 grams of 1.23 molar diisobutylaluminum hydride (DIBAH) in hexane, (i.e., 25% weight percent DIBAH). The reactor was maintained at 20° C. by cooling. N-butanol (11.16 grams) was added with stirring. After stirring for thirty minutes, 107.5 grams of 10.1% neodymium solution (neodymium neodecanoate) diluted with 160 grams of dry hexane, was charged to the reactor. The solution was stirred for another thirty minutes after which time 18.2 grams of allyl bromide was added. The cooling was stopped and the solution was allowed to warm up. A delayed exothermic reaction was noted. After twenty minutes, bring the solution temperatures to about 10° C. above ambient temperature. When the temperature ultimately dropped, the catalyst solution was aged by heating at 65° C. for ninety minutes. The catalyst prepared had a [butanol-DIBAH]Nd-allyl bromide-butadiene molar ratio of [2-13]-1-2-20, respectively, and a concentration of 0.025 molarity with respect to the neodymium.
Reaction SMILES: C=CC1C=CC=CC=1.[H][H].[C]=O.C1(CC2C=CC=CC=2)C=CC=CC=1.[C:26]1([CH:32]([CH3:35])[CH:33]=[O:34])[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.C1(CCC=O)C=CC=CC=1>C1C=CC=CC=1>[C:26]1([C@H:32]([CH3:35])[CH:33]=[O:34])[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1
Reactant: [H][H]
Reactant: CC(C=O)c1ccccc1
Agent: O=CCCc1ccccc1
Agent: [C]=O
Solvent: c1ccc(Cc2ccccc2)cc1
Solvent: C=Cc1ccccc1
Solvent: c1ccccc1
Product: C[C@H](C=O)c1ccccc1
Temperature: 60 °C
Reaction time: 42 h

Procedure:
In a 50 ml autoclave were charged 38.7 mg (0.0488 mmol) of (S,R)-biphemphos, 3.1 mg (0.012 mmol) of Rh(acac)(CO)2, and a solution of 1250 mg (12.0 mmol) of styrene in 2.4 ml of benzene, and hydrogen and carbon monoxide were fed thereto each to a partial pressure of 50 atm. The mixture was stirred at 60° C. for 42 hours. A conversion of the starting olefin and an aldehyde production ratio were determined by 1H-NMR (internal standard: diphenylmethane) analysis, and an optical purity (enantiomer excess) was determined by GLC analysis after conversion of the resulting optically active aldehyde into the corresponding carboxylic acid by Jones oxidation. As a result, the conversion of styrene was 100%, and the 2-phenylpropanal/3-phenylpropanal production ratio was 9:1. The 2-phenylpropanal produced had an optical purity of (S)-(+)-2-phenylpropanal of 94% ee.
Reaction SMILES: C[O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[C:9]([O:13][C:14]1[CH:19]=[CH:18][C:17](/[CH:20]=[CH:21]/[C:22]([OH:24])=[O:23])=[CH:16][CH:15]=1)=[C:8]([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[C:7]([CH2:31][CH2:32][C:33]([F:36])([F:35])[F:34])=[CH:6]2.B(Br)(Br)Br>C(Cl)Cl>[OH:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[C:9]([O:13][C:14]1[CH:15]=[CH:16][C:17](/[CH:20]=[CH:21]/[C:22]([OH:24])=[O:23])=[CH:18][CH:19]=1)=[C:8]([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[C:7]([CH2:31][CH2:32][C:33]([F:34])([F:35])[F:36])=[CH:6]2
Reactant: COc1ccc2c(Oc3ccc(/C=C/C(=O)O)cc3)c(-c3ccccc3)c(CCC(F)(F)F)cc2c1
Agent: BrB(Br)Br
Solvent: ClCCl
Product: O=C(O)/C=C/c1ccc(Oc2c(-c3ccccc3)c(CCC(F)(F)F)cc3cc(O)ccc23)cc1
Yield: 65.4 %

Procedure:
Methyl ether (128) (0.15 g, 0.31 mmol) was treated with BBr3 in CH2Cl2 to give the crude product as orange viscous oil, which was purified by reverse phase preparation HPLC on Agilent 1100 to afford 97 mg (67%) of the title compound (129) as a light yellow solid. mp 118-120° C. 1H NMR (400 MHz, CH3OH-d4): δ 2.15-2.30 (m, 2H), 2.80-2.90 (m, 2H), 6.26 (d, J=15.9 Hz, 1H), 6.57 (d, J=8.6 Hz, 2H), 7.00 (dd, J1=9.0 Hz, J2=2.3 Hz, 1H), 7.16-7.20 (m, 3H), 7.22-7.32 (m, 3H), 7.34 (d, J=8.8 Hz, 2H), 7.52 (d, J=15.9 Hz, 1H), 7.59 (s, 1H), 7.62 (d, J=9.1 Hz, 1H). LCMS (ESI): m/z 479 (M+H)+, m/z 477 (M−H)−. Anal. Calc for C28H21F3O4.0.25H2O: C, 69.63; H, 4.49. Found: C, 69.63; H, 4.41.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5](B(O)O)=[CH:4][CH:3]=1.Br[C:12]1[C:16]([Br:17])=[C:15]([NH:18][C:19]([C@@H:21]2[CH2:23][C@H:22]2[CH3:24])=[O:20])[S:14][N:13]=1>>[Br:17][C:16]1[C:12]([C:5]2[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=2)=[N:13][S:14][C:15]=1[NH:18][C:19]([C@@H:21]1[CH2:23][C@H:22]1[CH3:24])=[O:20]
Reactant: C[C@@H]1C[C@H]1C(=O)Nc1snc(Br)c1Br
Reactant: OB(O)c1ccc(F)cc1
Product: C[C@@H]1C[C@H]1C(=O)Nc1snc(-c2ccc(F)cc2)c1Br
Temperature: 70 °C
Reaction time: 24 h

Procedure:
Using a similar procedure to that of Preparation VI-3, but using 1.3 equivalents of 4-fluorophenylboronic acid to 1 equivalent of (R,R)—N-[3,4-dibromoisothiazol-5-yl]-2-methylcyclopropanecarboxamide and stirring the reaction mixture at 70° C. for 1 day affords (R,R)—N-[4-bromo-3-(4-fluorophenyl)isothiazol-5-yl]-2-methylcyclopropane-carboxamide. ES-MS: m/e 357.0 (m+1).
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([NH:8][N+]([O-])=O)[CH:3]=1.ClC1C=CN=C(N[N+]([O-])=[O:21])C=1>>[NH2:8][C:4]1[C:3]([OH:21])=[C:2]([Br:1])[CH:7]=[CH:6][N:5]=1
Reactant: O=[N+]([O-])Nc1cc(Cl)ccn1
Reactant: O=[N+]([O-])Nc1cc(Br)ccn1
Product: Nc1nccc(Br)c1O

Procedure:
By substituting 4-bromo-2-nitraminopyridine for the 4-chloro-2-nitraminopyridine in Example I-5, there is obtained 2-amino-4-bromo-3-pyridinol.
Reaction SMILES: [CH2:1]([C@:4]1([C:27]2[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=2)[CH2:9][CH2:8][N:7]([C@H:10]([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[CH:19]=[CH:20][C:21](=[O:25])[N:22]([CH3:24])[CH:23]=3)=[CH:14][CH:13]=2)[CH3:11])[C:6](=[O:26])[CH2:5]1)[CH:2]=[CH2:3].B.C1C[O:38]CC1>C1COCC1>[F:33][C:30]1[CH:31]=[CH:32][C:27]([C@@:4]2([CH2:1][CH2:2][CH2:3][OH:38])[CH2:9][CH2:8][N:7]([C@H:10]([C:12]3[CH:17]=[CH:16][C:15]([C:18]4[CH:19]=[CH:20][C:21](=[O:25])[N:22]([CH3:24])[CH:23]=4)=[CH:14][CH:13]=3)[CH3:11])[C:6](=[O:26])[CH2:5]2)=[CH:28][CH:29]=1
Reactant: C=CC[C@]1(c2ccc(F)cc2)CCN([C@@H](C)c2ccc(-c3ccc(=O)n(C)c3)cc2)C(=O)C1
Reactant: C1CCOC1
Agent: B
Product: C[C@@H](c1ccc(-c2ccc(=O)n(C)c2)cc1)N1CC[C@](CCCO)(c2ccc(F)cc2)CC1=O
Reaction time: 2 h
Yield: 2 %

Procedure:
To a solution of 5-(4-((S)-1-((S)-4-allyl-4-(4-fluorophenyl)-2-oxopiperidin-1-yl)ethyl)phenyl)-1-methylpyridin-2(1H)-one (45 mg, 0.10 mmol) in THF (3 mL) was added BH3/THF (0.3 mL, 1 M) at 0° C. under nitrogen atmosphere. The mixture was stirred for 2 h. The reaction was quenched with water. Aqueous NaOH solution (1 M, 0.6 mL) and H2O2 (0.3 mL□30%) were added to the above mixture. The resulting mixture was stirred for 1 h. The mixture was extracted with EtOAc and the combined organic phase was concentrated to give the crude product, which was purified by preparative HPLC to give 5-(4-((S)-1-((S)-4-(4-fluorophenyl)-4-(3-hydroxypropyl)-2-oxopiperidin-1-yl)ethyl)phenyl)-1-methylpyridin-2(1H)-one (1.0 mg, 2%). LC-MS Method 2, tR=1.63 min, m/z=463.1. 1H NMR (CDCl3): δ1.42 (t, 3H), 1.69 (m, 2H), 1.92 (m, 1H), 2.01 (m, 1H), 2.22 (m, 2H), 2.44 (d, 2H), 2.99 (m, 3H), 3.36 (m, 1H), 3.42 (t, 2H), 3.59 (s, 3H), 3.60 (m, 1H), 3.84 (m, 1H), 6.01 (q, 1H), 6.61 (d, 1H) □ 6.89 (m, 4H), 7.14 (m, 4H), 7.33 (d, 1H), 7.49 (m, 1H).
Reaction SMILES: Br[C:2]1[CH:3]=[N:4][CH:5]=[N:6][CH:7]=1.C(=O)([O-])[O-].[Na+].[Na+].[CH:14]([C:16]1[CH:17]=[C:18](B(O)O)[CH:19]=[CH:20][CH:21]=1)=[O:15]>C1(C)C=CC=CC=1.C(O)C.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[N:4]1[CH:3]=[C:2]([C:19]2[CH:18]=[CH:17][C:16]([CH:14]=[O:15])=[CH:21][CH:20]=2)[CH:7]=[N:6][CH:5]=1
Reactant: Brc1cncnc1
Reactant: O=Cc1cccc(B(O)O)c1
Agent: [Pd]
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: CCO
Product: O=Cc1ccc(-c2cncnc2)cc1
Temperature: 80 °C
Reaction time: 0.33 h
Yield: 59.7 %

Procedure:
5-Bromopyrimidine (159 mg, 1 mmol) was dissolved in toluene (5 mL) and treated with tetrakis(triphenylphosphine)-palladium(0) (116 mg, 0.1 equivalent) and a 2 M solution of sodium carbonate (1 mL, 2 equivalents). The mixture was stirred under an argon atmosphere for 20 min. followed by addition of 3-formylphenyl boronic acid (165 mg, 1.1 equivalensts) in ethanol (1 mL). The reaction was heated to 80° C. and stirred for 16 hrs. The mixture was filtered and partitioned between ethyl acetate and water. The organic layer was washed with brine, dried over magnesium sulfate, filtered, and the solvent was removed by evaporation. This material was purified using hexanes:dichloromethane (1:1) followed by dichloromethane:methanol (97:3) to give 110 mg (60%) of the title compound.
Reaction SMILES: [CH3:1][C:2]1[NH:3][CH:4]=[CH:5][N:6]=1.Cl[C:8]1[N:9]=[C:10]([NH:18][CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:11]2[C:16]([CH3:17])=[CH:15][S:14][C:12]=2[N:13]=1>>[CH3:1][C:2]1[N:3]([C:8]2[N:9]=[C:10]([NH:18][CH2:19][C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[C:11]3[C:16]([CH3:17])=[CH:15][S:14][C:12]=3[N:13]=2)[CH:4]=[CH:5][N:6]=1
Reactant: Cc1ncc[nH]1
Reactant: Cc1csc2nc(Cl)nc(NCc3ccccc3)c12
Product: Cc1csc2nc(-n3ccnc3C)nc(NCc3ccccc3)c12

Procedure:
Following the procedure of Example 97, the reaction of 2-methylimidazole with 2-chloro-5-methyl-4-benzylamino-thieno-[2,3-d]-pyrimidine gives 2-(2-methylimidazol-1-yl)-5-methyl-4-benzylamino-thieno-[2,3-d]-pyrimidine.
Reaction SMILES: [CH3:1][CH:2]1[CH2:10][C:9]2[C:4](=[CH:5][C:6]([N+:12]([O-:14])=O)=[C:7]([NH2:11])[CH:8]=2)[CH2:3]1.[N:15]#[C:16][NH2:17].[CH]Cl.[OH-].[Na+]>O>[CH3:1][CH:2]1[CH2:10][C:9]2[C:4](=[CH:5][C:6]3[N+:12]([O-:14])=[N:15][C:16]([NH2:17])=[N:11][C:7]=3[CH:8]=2)[CH2:3]1
Reactant: CC1Cc2cc(N)c([N+](=O)[O-])cc2C1
Reactant: N#CN
Agent: [CH]Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: CC1Cc2cc3nc(N)n[n+]([O-])c3cc2C1
Temperature: 100 °C
Reaction time: 3 h
Yield: 90.1 %

Procedure:
A mixture of nitroaniline 93 (3.0 g, 15.7 mmol) and cyanamide (2.6 g, 62.6 mmol) was mixed together at 80° C., cHCl (5 mL) added dropwise and the mixture heated at 100° C. for 3 h. A further three aliquots of cyanamide (0.5 g, 11.9 mmol) and cHCl (0.5 mL) were added over two hours. The mixture was cooled to 50° C., 7.5 M NaOH solution added until the mixture was strongly basic and the mixture stirred at 100° C. for 3 h. The mixture was cooled, diluted with water (100 mL), filtered, washed with water (2×30 mL), and dried. The residue was purified by chromatography, eluting with a gradient (0-15%) of MeOH/DCM, to give 1-oxide 94 (3.06 g, 90%) as a yellow powder: mp (MeOH/DCM) 275-277° C.; 1H NMR [(CD3)2SO] δ 7.90 (s, 1H, H-9), 7.31 (s, 1H, H-5), 7.10 (br s, 2H, NH2), 3.05-3.14 (m, 2H, CH2), 2.48-2.62 (m, 3H, H-7, CH2), 1.09 (d, J=6.3 Hz, 3H, CH3); 13C NMR [(CD3)2SO] δ 159.9, 153.7, 148.6, 142.1, 128.7, 120.0, 113.9, 41.4, 39.6, 34.3, 19.9. Anal. calcd for C11H12N4O: C, 61.1; H, 5.6; N, 25.9. Found: C, 61.3; H, 5.6; N, 26.2%.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[N:22]([CH2:23][C:24]#[C:25][CH3:26])[C:21]3[C:20](=[O:27])[N:19](COC(=O)C(C)(C)C)[C:18](=[O:36])[N:17](COC(=O)C(C)(C)C)[C:16]=3[N:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].Cl>O1CCCC1.CO>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][N:11]([C:14]2[N:22]([CH2:23][C:24]#[C:25][CH3:26])[C:21]3[C:20](=[O:27])[NH:19][C:18](=[O:36])[NH:17][C:16]=3[N:15]=2)[CH2:12][CH2:13]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC#CCn1c(N2CCN(C(=O)OC(C)(C)C)CC2)nc2c1c(=O)n(COC(=O)C(C)(C)C)c(=O)n2COC(=O)C(C)(C)C
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CO
Product: CC#CCn1c(N2CCN(C(=O)OC(C)(C)C)CC2)nc2[nH]c(=O)[nH]c(=O)c21
Temperature: 25 °C
Reaction time: 1 h
Yield: 100.3 %

Procedure:
4-[7-(2-Butynyl)-1,3-bis-(2,2-dimethylpropionyloxymethyl)-2,6-dioxo 2,3,6,7-tetrahydro-1H-purin-8-yl]piperazine-1-carboxylic acid tert-butyl ester (1.9 g) was dissolved in a solvent mixture of tetrahydrofuran (20 ml) and methanol (10 ml), and sodium hydride (0.31 g) was added to the solution. The mixture was stirred at room temperature for 1 hour. The reaction mixture was neutralized with 2 N hydrochloric acid and extracted with ethyl acetate. The organic layer was concentrated by distillation to give 1.2 g of the title compound.
Reaction SMILES: [CH2:1]([C:3]1[S:4][C:5]([C:15]2[CH:20]=[CH:19][N+:18]([O-])=[CH:17][CH:16]=2)=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([CH3:14])[CH:9]=2)[N:7]=1)[CH3:2].C(=O)([O-])O.[Na+].P(Cl)(Cl)([Cl:29])=O>>[Cl:29][C:19]1[CH:20]=[C:15]([C:5]2[S:4][C:3]([CH2:1][CH3:2])=[N:7][C:6]=2[C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([CH3:14])[CH:9]=2)[CH:16]=[CH:17][N:18]=1
Reactant: O=P(Cl)(Cl)Cl
Reactant: CCc1nc(-c2cccc(C)c2)c(-c2cc[n+]([O-])cc2)s1
Agent: O=C([O-])O
Agent: [Na+]
Product: CCc1nc(-c2cccc(C)c2)c(-c2ccnc(Cl)c2)s1
Yield: 81 %

Procedure:
A solution of 4-[2-ethyl-4-(3-methylphenyl)-1,3-thiazol-5-yl]pyridine N-oxide (1.00 g, 3.37 mmol) in phosphorus oxychloride (6.5 mL) was stirred at 100° C. for 2 hours. The reaction solution was cooled, and poured into a saturated aqueous sodium hydrogen carbonate solution, and extracted with ethyl acetate. The extracts were washed with brine, then, dried, and concentrated. The residue was purified by silica gel column chromatography (hexane-ethyl acetate=2:1) to obtain a title compound (0.90 g, yield 81%).
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]2=[N:12][N:13]=[C:14]([C:15]3[CH:19]=[CH:18][O:17][N:16]=3)[N:4]2[N:3]=1.[OH:20][CH2:21][C:22]1[N:23]([CH2:27][O:28][CH2:29][CH2:30][Si:31]([CH3:34])([CH3:33])[CH3:32])[N:24]=[CH:25][N:26]=1>>[O:17]1[CH:18]=[CH:19][C:15]([C:14]2[N:4]3[N:3]=[C:2]([O:20][CH2:21][C:22]4[N:23]([CH2:27][O:28][CH2:29][CH2:30][Si:31]([CH3:34])([CH3:33])[CH3:32])[N:24]=[CH:25][N:26]=4)[C:11]4[C:6]([C:5]3=[N:12][N:13]=2)=[CH:7][CH:8]=[CH:9][CH:10]=4)=[N:16]1
Reactant: C[Si](C)(C)CCOCn1ncnc1CO
Reactant: Clc1nn2c(-c3ccon3)nnc2c2ccccc12
Product: C[Si](C)(C)CCOCn1ncnc1COc1nn2c(-c3ccon3)nnc2c2ccccc12

Procedure:
The title-compound was prepared from 6-chloro-3-(3-isoxazolyl)-1,2,4-triazolo[3,4-a]phthalazine (described in Example 34, part b) and 3-(hydroxymethyl)-2-{[2-(trimethylsilyl)ethoxyjmethyl}-1,2,4-triazole (described in Example 45, part c) following the procedure described in Example 45, part d, 1H NMR (360 MHz, CDCl3) δ 0.00 (9H, s, 3 of CH3), 0.88 (2H, q, J=8.4 Hz, CH2), 3.67 (2H, t, J=8.3 Hz, CH2), 5.84 (2H, s, CH2), 5.92 (2H, s, CH2), 7.30 (1H, d, J=1.7 Hz, Ar—H), 7.89 (1H, t, J=7.1 Hz, Ar—H), 7.96 (1H, s, Ar—H), 8.02 (1H, t, J=7.6 Hz, Ar—H), 8.32 (1H, d, J=8.2 Hz, Ar—H), 8.70 (1H, s, Ar—H), 8.75 (1H, d, J=8.2 Hz, Ar—H).