Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([C:4]1[O:5][C:6]2[C:11]([C:12](=[O:14])[CH:13]=1)=[C:10]([O:15][CH2:16][CH:17]([OH:34])[CH2:18][O:19][C:20]1[CH:29]=[CH:28][CH:27]=[C:26]3[C:21]=1[C:22](=[O:33])[CH:23]=[C:24]([C:30]([OH:32])=[O:31])[O:25]3)[CH:9]=[CH:8][CH:7]=2)([OH:3])=[O:2].[C:35]([NH:54][C@H:55]([C:59]([O:61][CH2:62][CH:63]([CH2:70][O:71][C:72](=[O:90])[CH2:73][CH2:74][CH2:75][CH2:76][CH2:77][CH2:78][CH2:79][CH2:80][CH2:81][CH2:82][CH2:83][CH2:84][CH2:85][CH2:86][CH2:87][CH2:88][CH3:89])[CH2:64][CH2:65][CH2:66][C:67](O)=[O:68])=[O:60])[CH:56]([CH3:58])[CH3:57])([C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1)([C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1)[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1.CN(C1C=CC=CN=1)C.C1CCC(N=C=NC2CCCCC2)CC1>ClCCl>[C:35]([NH:54][C@H:55]([C:59]([O:61][CH2:62][CH:63]([CH2:70][O:71][C:72](=[O:90])[CH2:73][CH2:74][CH2:75][CH2:76][CH2:77][CH2:78][CH2:79][CH2:80][CH2:81][CH2:82][CH2:83][CH2:84][CH2:85][CH2:86][CH2:87][CH2:88][CH3:89])[CH2:64][CH2:65][CH2:66][C:67]([O:34][CH:17]([CH2:16][O:15][C:10]1[CH:9]=[CH:8][CH:7]=[C:6]2[C:11]=1[C:12](=[O:14])[CH:13]=[C:4]([C:1]([OH:3])=[O:2])[O:5]2)[CH2:18][O:19][C:20]1[CH:29]=[CH:28][CH:27]=[C:26]2[C:21]=1[C:22](=[O:33])[CH:23]=[C:24]([C:30]([OH:32])=[O:31])[O:25]2)=[O:68])=[O:60])[CH:56]([CH3:58])[CH3:57])([C:36]1[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=1)([C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1)[C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1
Reactant: O=C(O)c1cc(=O)c2c(OCC(O)COc3cccc4oc(C(=O)O)cc(=O)c34)cccc2o1
Reactant: CCCCCCCCCCCCCCCCCC(=O)OCC(CCCC(=O)O)COC(=O)[C@@H](NC(c1ccccc1)(c1ccccc1)c1ccccc1)C(C)C
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: CN(C)c1ccccn1
Solvent: ClCCl
Product: CCCCCCCCCCCCCCCCCC(=O)OCC(CCCC(=O)OC(COc1cccc2oc(C(=O)O)cc(=O)c12)COc1cccc2oc(C(=O)O)cc(=O)c12)COC(=O)[C@@H](NC(c1ccccc1)(c1ccccc1)c1ccccc1)C(C)C
Reaction time: 72 h

Procedure:
To a solution of the dibenzyl ester of 1,3-bis-(2-carboxychromon-5-yloxy)propan-2-ol (270 mg, 0.42 mmole), 5-(N-Trityl-L-valyloxymethyl)-6-stearoyloxyhexanoic acid (323 mg, 0.42 mmol) and dimethylaminopyridine (6 mg, 0.05 mmol) in dichloromethane was added DCC (92 mg, 0.45 mmol). After 3 days, the reaction mixture was filtered through Celite and the filtrate was washed with sodium hydrogen carbonate aqueous solution and dried. The product dibenzyl ester of 2-[5-(N-trityl-L-valyloxymethyl)-6-stearoyloxyhexanoyloxy]-1,3-bis-(2-carboxychromon-5-yloxy)propane was isolated from silica gel column chromatography. 250 mg.
Reaction SMILES: [ClH:1].Cl.[NH:3]1[CH2:6][CH:5]([C:7]2[C:8]([O:28][CH3:29])=[C:9]([CH:15]([N:17]3[C:21]4=[N:22][CH:23]=[N:24][C:25]([NH2:26])=[C:20]4[C:19]([CH3:27])=[N:18]3)[CH3:16])[CH:10]=[C:11](Cl)[C:12]=2[F:13])[CH2:4]1.[CH3:30][C:31]([CH3:33])=O.C(N(CC)CC)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl>[Cl:1][C:7]1([CH:5]2[CH2:6][N:3]([CH:31]([CH3:33])[CH3:30])[CH2:4]2)[C:12]([F:13])=[CH:11][CH:10]=[C:9]([CH:15]([N:17]2[C:21]3=[N:22][CH:23]=[N:24][C:25]([NH2:26])=[C:20]3[C:19]([CH3:27])=[N:18]2)[CH3:16])[CH:8]1[O:28][CH3:29]
Reactant: Cl
Reactant: CC(C)=O
Reactant: COc1c(C(C)n2nc(C)c3c(N)ncnc32)cc(Cl)c(F)c1C1CNC1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: COC1C(C(C)n2nc(C)c3c(N)ncnc32)=CC=C(F)C1(Cl)C1CN(C(C)C)C1
Temperature: 25 °C
Reaction time: 2 h
Yield: 105.3 %

Procedure:
To a mixture of 1-[1-(3-azetidin-3-yl-5-chloro-4-fluoro-2-methoxyphenyl)ethyl]-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine dihydrochloride (0.90 g, 1.9 mmol, Example 67, step 1), acetone (1.0 mL, 14 mmol) and triethylamine (2.5 mL, 18 mmol) in methylene chloride (20 mL) was added sodium triacetoxyborohydride resin (2.5 g, 5.8 mmol). The mixture was stirred at room temperature for 2 h, then filtered, washed with water, dried over MgSO4, filtered and concentrated to give crude product (870 mg, 100%). LCMS calculated for C21H27ClFN6O (M+H)+: m/z=433.2; Found: 433.1
Reaction SMILES: [N:1]([CH:4]([C:6]1[CH:7]=[N:8][CH:9]=[CH:10][C:11]=1[C:12]1[C:17]2[S:18][CH:19]=[CH:20][C:16]=2[CH:15]=[CH:14][CH:13]=1)[CH3:5])=[N+]=[N-].C(O)=O.NN>[Ni].C(O)C>[S:18]1[CH:19]=[CH:20][C:16]2[CH:15]=[CH:14][CH:13]=[C:12]([C:11]3[CH:10]=[CH:9][N:8]=[CH:7][C:6]=3[CH:4]([NH2:1])[CH3:5])[C:17]1=2
Reactant: CC(N=[N+]=[N-])c1cnccc1-c1cccc2ccsc12
Agent: [Ni]
Agent: NN
Solvent: O=CO
Solvent: CCO
Product: CC(N)c1cnccc1-c1cccc2ccsc12
Temperature: 25 °C
Reaction time: 1 h
Yield: 100.4 %

Procedure:
Add Raney Nickel (1.38 g, 2.35 mmol) into a solution of 3-(1-azido-ethyl)-4-benzo[b]thiophen-7-yl-pyridine (0.66 g, 2.35 mmol) in ethanol (10 mL), formic acid (1.08 g, 23.54 mmol), and hydrazine (754.4 mg, 23.54 mmol) in a 50-mL round bottom flask in an ice bath. Stir the mixture at RT for 1 h and filter the Raney Nickel. Dilute the filtrate with ammonium hydroxide. Extract the product into chloroform. Wash the organic phase with water, dry over sodium sulfate, and concentrate to give the title compound as a brown oil (0.6 g, 100%). MS (ES) m/z 255 [M+1]+.
Reaction SMILES: C1(C2OC(C(F)(F)F)=C(C(NC3C=CC(C4C=CC(C([C@@H]5CCC[C@H]5C(O)=O)=O)=CC=4)=CC=3)=O)N=2)C=CC=CC=1.[C:41]1([C:47]2[O:48][C:49]([C:78]([F:81])([F:80])[F:79])=[C:50]([C:52]([NH:54][C:55]3[CH:60]=[CH:59][C:58]([C:61]4[CH:66]=[CH:65][C:64]([C:67]([CH:69]5[CH2:74][CH2:73][CH2:72][CH2:71][CH:70]5[C:75]([OH:77])=[O:76])=[O:68])=[CH:63][CH:62]=4)=[CH:57][CH:56]=3)=[O:53])[N:51]=2)[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1.C1(C2OC(C(F)(F)F)=C(C(O)=O)N=2)C=CC=CC=1.NC1C=CC(C2C=CC(C([C@H]3CCCC[C@H]3C(O)=O)=O)=CC=2)=CC=1>>[C:41]1([C:47]2[O:48][C:49]([C:78]([F:80])([F:81])[F:79])=[C:50]([C:52]([NH:54][C:55]3[CH:56]=[CH:57][C:58]([C:61]4[CH:66]=[CH:65][C:64]([C:67]([C@@H:69]5[CH2:74][CH2:73][CH2:72][CH2:71][C@@H:70]5[C:75]([OH:77])=[O:76])=[O:68])=[CH:63][CH:62]=4)=[CH:59][CH:60]=3)=[O:53])[N:51]=2)[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1
Reactant: O=C(Nc1ccc(-c2ccc(C(=O)C3CCCCC3C(=O)O)cc2)cc1)c1nc(-c2ccccc2)oc1C(F)(F)F
Agent: Nc1ccc(-c2ccc(C(=O)[C@H]3CCCC[C@H]3C(=O)O)cc2)cc1
Agent: O=C(Nc1ccc(-c2ccc(C(=O)[C@@H]3CCC[C@H]3C(=O)O)cc2)cc1)c1nc(-c2ccccc2)oc1C(F)(F)F
Agent: O=C(O)c1nc(-c2ccccc2)oc1C(F)(F)F
Product: O=C(Nc1ccc(-c2ccc(C(=O)[C@@H]3CCCC[C@@H]3C(=O)O)cc2)cc1)c1nc(-c2ccccc2)oc1C(F)(F)F

Procedure:
With a method similar to that used for the preparation of racemic trans-2-{4′-[(2-phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-biphenyl-4-carbonyl}-cyclopentanecarboxylic acid above, racemic 2-{4′-[(2-phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-biphenyl-4-carbonyl}-cyclohexanecarboxylic acid was prepared from 2-phenyl-5-trifluoromethyl-oxazole-4-carboxylic acid and cis-2-(4′-amino-biphenyl-4-carbonyl)-cyclohexanecarboxylic acid. The racemic product was separated by chiral SFC to afford (1S,2R)-2-{4′-[(2-phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-biphenyl-4-carbonyl}-cyclohexanecarboxylic acid (or enantiomer). [α]D: −23.8° in DMSO. LCMS calcd for C31H25F3N2O5 (m/e) 562, obsd 563 (M+H).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:17]=[C:16]([O:18][CH3:19])[CH:15]=[CH:14][C:4]=1[CH2:5][NH:6][C:7]1[CH:12]=[CH:11][C:10]([F:13])=[CH:9][N:8]=1.[F:20][C:21]1[C:26]([Br:27])=[CH:25][C:24]([S:28](Cl)(=[O:30])=[O:29])=[CH:23][CH:22]=1>>[Br:27][C:26]1[CH:25]=[C:24]([S:28]([N:6]([CH2:5][C:4]2[CH:14]=[CH:15][C:16]([O:18][CH3:19])=[CH:17][C:3]=2[O:2][CH3:1])[C:7]2[CH:12]=[CH:11][C:10]([F:13])=[CH:9][N:8]=2)(=[O:29])=[O:30])[CH:23]=[CH:22][C:21]=1[F:20]
Reactant: O=S(=O)(Cl)c1ccc(F)c(Br)c1
Reactant: COc1ccc(CNc2ccc(F)cn2)c(OC)c1
Product: COc1ccc(CN(c2ccc(F)cn2)S(=O)(=O)c2ccc(F)c(Br)c2)c(OC)c1

Procedure:
The title compound was prepared according to the method described for Preparation 11 using N-(2,4-dimethoxybenzyl)-5-fluoropyridin-2-amine (Preparation 20) and 4-fluoro-5-bromobenzenesulfonyl chloride at 40° C. The residue was purified by silica gel column chromatography eluting with 10% EtOAc in heptanes.
Reaction SMILES: NC1C=CC=CC=1N[S:9]([C:12]1[S:16][C:15]2[CH:17]=[CH:18][CH:19]=[CH:20][C:14]=2[CH:13]=1)(=[O:11])=[O:10].C[O:22]C1C=CC(S(C(C)C)(=O)=O)=CC=1S(Cl)(=O)=O>C(Cl)Cl.N1C=CC=CC=1>[S:16]1[C:12]([S:9]([OH:10])(=[O:11])=[O:22])=[CH:13][C:14]2[CH:20]=[CH:19][CH:18]=[CH:17][C:15]1=2
Reactant: Nc1ccccc1NS(=O)(=O)c1cc2ccccc2s1
Reactant: COc1ccc(S(=O)(=O)C(C)C)cc1S(=O)(=O)Cl
Solvent: c1ccncc1
Solvent: ClCCl
Product: O=S(=O)(O)c1cc2ccccc2s1
Temperature: 25 °C
Reaction time: 8 h
Yield: 214.7 %

Procedure:
To a solution of benzo[b]thiophene-2-sulfonic acid (2-aminophenyl)-amide (1 mmol) (prepared as in example 1) in DCM (2 mL) and pyridine (2 mL), 2-methoxy-5-(propane-2-sulfonyl)benzenesulfonyl chloride (1.1 mmol) was added at RT and the reaction mixture was then allowed to stir at RT overnight. The reaction mixture was then diluted with DCM (10 mL). The organic phase was washed with 10% aqueous HCl (10 mL), water (10 mL) and brine (10 mL). The organic phase was dried over anhydrous sodium sulfate, and concentrated under vacuum. The residue obtained was purified by flash column chromatography eluting with DCM/EtOAc to obtain 460 mg of benzo[b]thiophene-2-sulfonic acid {2-[2-methoxy-5-(propane-2 sulfonyl) benzenesulfonylamino]phenyl-amide. Tr 1.09 min; MS: 581.4 (M+1)+. 1H NMR (DMSO-d6, 400 MHz): δ 0.97 (d, 6H), 3.58 (m, 1H), 4.02 (s, 3H), 6.84 (dd, 1H), 7.96 (td, 1H), 7.10 (td, 1H), 7.23 (dd, 1H), 7.44-7.54 (m, 3H), 7.86 (d, 1H), 7.90 (s, 1H), 7.96 (d, 1H), 8.03 (dd, 2H), 9.22 (bs, 1H), 9.79 (s, 1H) ppm.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([CH:8]=O)[N:3]=1.[NH:10]1[CH2:15][CH2:14][O:13][CH:12]([CH2:16][CH2:17][OH:18])[CH2:11]1>>[Cl:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([CH2:8][N:10]2[CH2:15][CH2:14][O:13][CH:12]([CH2:16][CH2:17][OH:18])[CH2:11]2)[N:3]=1
Reactant: O=Cc1nccc(Cl)n1
Reactant: OCCC1CNCCO1
Product: OCCC1CN(Cc2nccc(Cl)n2)CCO1

Procedure:
The title compound was prepared as described in Example 106, Step 1 with 4-chloropyrimidine-2-carbaldehyde (110 mg, 0.84 mmol) and 2-morpholin-2-ylethanol (100 mg, 0.70 mmol) as starting materials.
Reaction SMILES: [CH2:1]([NH:4][C:5]([C:7]1[N:8]=[CH:9][N:10]2[C:16]3[CH:17]=[CH:18][CH:19]=[C:20]([Cl:21])[C:15]=3[C:14](=[O:22])[N:13]3[CH2:23][CH2:24][CH2:25][C@H:12]3[C:11]=12)=[O:6])[C:2]#[CH:3].IN1C(=O)CCC1=O.[CH2:34]([NH:37][CH2:38][CH2:39][CH3:40])[CH2:35][CH3:36]>C(O)(=O)C>[Cl:21][C:20]1[C:15]2[C:14](=[O:22])[N:13]3[CH2:23][CH2:24][CH2:25][C@H:12]3[C:11]3[N:10]([CH:9]=[N:8][C:7]=3[C:5]3[O:6][C:2]([CH2:3][N:37]([CH2:38][CH2:39][CH3:40])[CH2:34][CH2:35][CH3:36])=[CH:1][N:4]=3)[C:16]=2[CH:17]=[CH:18][CH:19]=1
Reactant: CCCNCCC
Reactant: C#CCNC(=O)c1ncn2c1[C@@H]1CCCN1C(=O)c1c(Cl)cccc1-2
Agent: O=C1CCC(=O)N1I
Solvent: CC(=O)O
Product: CCCN(CCC)Cc1cnc(-c2ncn3c2[C@@H]2CCCN2C(=O)c2c(Cl)cccc2-3)o1
Temperature: 25 °C
Reaction time: 12 h
Yield: 47.7 %

Procedure:
A solution of 1.07 g (0.003 mol) of (S)-8-chloro-9-oxo-11,12,13,13a-tetrahydro-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]-benzodiazepine-1-carboxylic acid prop-2-ynylamide in 10 ml of acetic acid was treated with 1.01 g (0.0045 mol) of N-iodosuccinimide. After stirring at room temperature for 12 hrs. the mixture was heated to 50° for a further 4 hrs. The dark suspension obtained was completely freed from solvent in a vacuum and dried azeotropically several times with toluene. The brown residue was dissolved in 10 ml of THF, treated at room temperature with 10 ml (0.073 mol) of dipropylamine and stirred at 50° for 2 hrs. The suspension obtained was completely freed from the solvents and the residue was partitioned between ethyl acetate and 1N aqueous hydrochloric acid and extracted. The acidic phase was made basic and extracted with ethyl acetate. The organic phase was concentrated, the pale brown product was chromatographed over silica gel with dichloromethane/methanol 95:5 as the eluent and digested with diethyl ether. There was obtained 0.65 g (48%) of (S)-8-chloro-1-(5-dipropylaminomethyl-oxazol-2-yl)-11,12,13,13a-tetrahydro-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]-benzodiazepin-9-one; [α]D20 =+11.5° (MeOH, c=1%)
Reaction SMILES: [CH:1]([C:3]1[CH:8]=[C:7]([C:9]2[C:14]3[C:15]([O:37][CH3:38])=[N:16][N:17]([C:18]([C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=4)([C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)[C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)[C:13]=3[CH:12]=[C:11]([NH:39][C:40]([NH:42][C@@H:43]([C:45]3[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=3)[CH3:44])=[O:41])[N:10]=2)[CH:6]=[CH:5][N:4]=1)=[O:2].[BH4-].[Na+].Cl>CO>[OH:2][CH2:1][C:3]1[CH:8]=[C:7]([C:9]2[C:14]3[C:15]([O:37][CH3:38])=[N:16][N:17]([C:18]([C:19]4[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=4)([C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=4)[C:25]4[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=4)[C:13]=3[CH:12]=[C:11]([NH:39][C:40]([NH:42][C@@H:43]([C:45]3[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=3)[CH3:44])=[O:41])[N:10]=2)[CH:6]=[CH:5][N:4]=1
Reactant: COc1nn(C(c2ccccc2)(c2ccccc2)c2ccccc2)c2cc(NC(=O)N[C@H](C)c3ccccc3)nc(-c3ccnc(C=O)c3)c12
Agent: Cl
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Product: COc1nn(C(c2ccccc2)(c2ccccc2)c2ccccc2)c2cc(NC(=O)N[C@H](C)c3ccccc3)nc(-c3ccnc(CO)c3)c12
Temperature: 25 °C
Reaction time: 2 h

Procedure:
(R)-1-(4-(2-formyl pyridin-4-yl)-3-methoxy-1-trityl-1H-pyrazolo[4,3-c]pyridin-6-yl)-3-(1-phenylethyl)urea (60 mg, 0.091 mmol, prepared from intermediate 51B by Scheme 3/Method A) was taken up in MeOH (2 ml) and sodium borohydride (3.79 mg, 0.100 mmol) was added. The reaction was allowed to stir at rt for 2 hours—until complete by LCMS. 1 ml of 2N HCl was added and the mixture was concentrated in vacuo. Reaction products were carrried forward without purification. MS: [M+H]+ m/z 661.
Reaction SMILES: [NH2:1][CH:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH:10]([C:22]2[CH:27]=[CH:26][C:25]([Cl:28])=[C:24]([Cl:29])[CH:23]=2)[CH2:11][N:12]([CH3:21])[C:13](=[O:20])[C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH2:4][CH2:3]1.C(N(CC)CC)C.[C:37](OC(=O)C)(=[O:39])[CH3:38]>ClCCl>[C:37]([NH:1][CH:2]1[CH2:3][CH2:4][N:5]([CH2:8][CH2:9][CH:10]([C:22]2[CH:27]=[CH:26][C:25]([Cl:28])=[C:24]([Cl:29])[CH:23]=2)[CH2:11][N:12]([CH3:21])[C:13](=[O:20])[C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH2:6][CH2:7]1)(=[O:39])[CH3:38]
Reactant: CC(=O)OC(C)=O
Reactant: CN(CC(CCN1CCC(N)CC1)c1ccc(Cl)c(Cl)c1)C(=O)c1ccccc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(=O)NC1CCN(CCC(CN(C)C(=O)c2ccccc2)c2ccc(Cl)c(Cl)c2)CC1
Reaction time: 0.5 h

Procedure:
To a solution of N-[4-(4-aminopiperidino)-2-(3,4-dichlorophenyl)butyl]-N-methylbenzamide (1.5 g) in dichloromethane (35 mL) was added triethylamine (0.60 mL) and acetic anhydride (0.41 mL), and the resulting solution was allowed to stir for 30 minutes. The mixture was diluted with dichloromethane and was washed (0.3 N sodium hydroxide, water), dried, and evaporated. The material was dissolved in toluene and the resulting solution was evaporated to give the title compound (1.63 g) as a white solid; MS: m/z=476(M+1). Analysis for C25H31Cl2N3O2.0.2 C6H5CH3 : Calculated: C, 64.07; H, 6.63; N, 8.49; Found: C, 64.04; H, 6.59; N, 8.32.
Reaction SMILES: [CH3:1][S:2]Cl.[Na].[OH:5][C:6]1[CH:11]=[C:10]([CH3:12])[O:9][C:8](=[O:13])[CH:7]=1>C(Cl)Cl>[OH:5][C:6]1[CH:11]=[C:10]([CH3:12])[O:9][C:8](=[O:13])[C:7]=1[S:2][CH3:1]
Reactant: CSCl
Reactant: Cc1cc(O)cc(=O)o1
Agent: [Na]
Solvent: ClCCl
Product: CSc1c(O)cc(C)oc1=O
Temperature: 25 °C
Reaction time: 4 h
Yield: 58 %

Procedure:
Methanesulfenyl chloride (21.6 g., 0.261 mol) dissolved in methylene chloride (100 ml.) was added to a rapidly stirred slurry of the monosodium salt of 4-hydroxy-6-methyl-2-pyrone (38.6 g., 0.261 mol) in methylene chloride (500 ml.) over a period of 35 minutes. The reaction temperature was maintained at 25°C. with cooling during the addition; then stirring was continued at ambient temperature for 4 hours. The methylene chloride was removed by distillation in vacuo and the residue triturated with water (200 ml.) to remove the by-product sodium chloride. The crude product was removed by filtration, 26.0 g., m. 127°-134°C., 58 percent yield; after recrystallization from 2-propanol, 17.2 g., m. 139°-140.5°C., 38 percent yield
Reaction SMILES: [CH2:1]([C:3]([C:28]1[CH:33]=[CH:32][C:31](B2OC(C)(C)C(C)(C)O2)=[C:30]([CH3:43])[CH:29]=1)([C:6]1[CH:11]=[CH:10][C:9]([CH2:12][CH2:13][C:14]([O:23][CH2:24][O:25][CH3:26])([C:19]([F:22])([F:21])[F:20])[C:15]([F:18])([F:17])[F:16])=[C:8]([CH3:27])[CH:7]=1)[CH2:4][CH3:5])[CH3:2].[CH3:44][O:45][C:46](=[O:55])[CH2:47][C:48]1[CH:49]=[N:50][CH:51]=[C:52](Br)[CH:53]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>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.O>[CH3:44][O:45][C:46](=[O:55])[CH2:47][C:48]1[CH:49]=[N:50][CH:51]=[C:52]([C:31]2[CH:32]=[CH:33][C:28]([C:3]([CH2:1][CH3:2])([C:6]3[CH:11]=[CH:10][C:9]([CH2:12][CH2:13][C:14]([O:23][CH2:24][O:25][CH3:26])([C:19]([F:22])([F:20])[F:21])[C:15]([F:18])([F:16])[F:17])=[C:8]([CH3:27])[CH:7]=3)[CH2:4][CH3:5])=[CH:29][C:30]=2[CH3:43])[CH:53]=1
Reactant: COC(=O)Cc1cncc(Br)c1
Reactant: CCC(CC)(c1ccc(CCC(OCOC)(C(F)(F)F)C(F)(F)F)c(C)c1)c1ccc(B2OC(C)(C)C(C)(C)O2)c(C)c1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=P([O-])([O-])[O-]
Agent: [K+]
Solvent: O
Product: CCC(CC)(c1ccc(CCC(OCOC)(C(F)(F)F)C(F)(F)F)c(C)c1)c1ccc(-c2cncc(CC(=O)OC)c2)c(C)c1
Temperature: 90 °C
Reaction time: 3 h
Yield: 80.3 %

Procedure:
Degassed N,N-dimethylformamide (0.37 mL) was added to 2-(4-{1-ethyl-1-[3-methyl-4-(4,4,4-trifluoro-3-methoxymethoxy-3-trifluoromethyl-butyl)-phenyl]-propyl}-2-methyl-phenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (Example 108-(1); 38.4 mg, 0.0623 mmol), (5-bromo-pyridin-3-yl)acetic acid methyl ester (Example 24-(2); 19.9 mg, 0.0865 mmol), tetrakis(triphenylphosphine)palladium (0) (9.0 mg, 0.0078 mmol) and potassium phosphate (28.2 mg, 0.133 mmol). After replacement with nitrogen, the mixture was heated while stirring at an external temperature of 85 to 95° C. for three hours. Water was added to the reaction mixture, followed by extraction with diethyl ether. The extract was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The residue was purified by silica gel chromatography (hexane/ethyl acetate=2/1) to give the title compound (32 mg, 80%).
Reaction SMILES: [F:1][C:2]([C:11]1[CH:16]=[CH:15][C:14]([N:17]2[C:26](=[O:27])[C:25]3[C:20](=[N+:21]([O-:28])[CH:22]=[CH:23][CH:24]=3)C2=O)=[C:13]([CH3:29])[CH:12]=1)([C:7]([F:10])([F:9])[F:8])[C:3]([F:6])([F:5])[F:4].[CH:30]([NH2:33])([CH3:32])[CH3:31].C1C[O:37][CH2:36]C1>>[F:1][C:2]([C:11]1[CH:16]=[CH:15][C:14]([NH:17][C:26]([CH:25]2[C:24](=[C:36]=[O:37])[CH:23]=[CH:22][N+:21]([O-:28])=[C:20]2[NH:33][CH:30]([CH3:32])[CH3:31])=[O:27])=[C:13]([CH3:29])[CH:12]=1)([C:3]([F:4])([F:5])[F:6])[C:7]([F:10])([F:8])[F:9]
Reactant: CC(C)N
Reactant: C1CCOC1
Reactant: Cc1cc(C(F)(C(F)(F)F)C(F)(F)F)ccc1N1C(=O)c2ccc[n+]([O-])c2C1=O
Product: Cc1cc(C(F)(C(F)(F)F)C(F)(F)F)ccc1NC(=O)C1C(=C=O)C=C[N+]([O-])=C1NC(C)C
Yield: 63 %

Procedure:
In 10 ml of THF was dissolved 400 mg of N-[4-(heptafluoro-2-propyl)-2-methylphenyl]pyridine-2,3-dicarboximide-1-oxide, followed by adding thereto 200 mg of isopropylamine, and the resulting mixture was stirred at room temperature for 5 hours. After completion of the reaction, the solvent was distilled off under reduced pressure and the resulting residue was purified by a silica gel column chromatography using ethyl acetate/n-hexane as an eluent, to obtain 290 mg of the desired compound as white crystals.
Reaction SMILES: [CH2:1]([C:8]1[N:12]=[C:11]([NH2:13])[NH:10][N:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[O:14]1[C:18]2[CH:19]=[CH:20][C:21]([C:23](=O)[CH2:24][C:25](OCC)=[O:26])=[CH:22][C:17]=2[O:16][CH2:15]1.CC1C=CC(S(O)(=O)=O)=CC=1>CCCCO>[O:14]1[C:18]2[CH:19]=[CH:20][C:21]([C:23]3[NH:13][C:11]4[N:10]([N:9]=[C:8]([CH2:1][C:2]5[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=5)[N:12]=4)[C:25](=[O:26])[CH:24]=3)=[CH:22][C:17]=2[O:16][CH2:15]1
Reactant: CCOC(=O)CC(=O)c1ccc2c(c1)OCO2
Reactant: Nc1nc(Cc2ccccc2)n[nH]1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: CCCCO
Product: O=c1cc(-c2ccc3c(c2)OCO3)[nH]c2nc(Cc3ccccc3)nn12
Reaction time: 8 h
Yield: 25.4 %

Procedure:
To a solution of 3-benzyl-1H-1,2,4-triazol-5-amine (100 mg, 0.57 mmol) in n-BuOH (3 ml) was added ethyl 3-(2H-1,3-benzodioxol-5-yl)-3-oxopropanoate (200 mg, 0.85 mmol) and 4-methylbenzene-1-sulfonic acid (4 mg, 0.02 mmol). After stirring overnight at reflux, the solids were collected by filtration and washed with ethyl acetate (3×10 mL), methanol (3×10 ml) and dried to give 5-(benzo[d][1,3]dioxol-5-yl)-2-benzyl-[1,2,4]triazolo[1,5-α]pyrimidin-7(4H)-one as a white solid (50.2 mg, 25%).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([C:9](=O)[CH2:10][C:11]2[CH:16]=[CH:15][C:14]([N:17]([CH3:19])[CH3:18])=[CH:13][CH:12]=2)[C:5](F)=[N:6][CH:7]=1.C(O)C.[NH2:24][NH2:25]>O>[Br:1][C:2]1[CH:3]=[C:4]2[C:9]([CH2:10][C:11]3[CH:16]=[CH:15][C:14]([N:17]([CH3:19])[CH3:18])=[CH:13][CH:12]=3)=[N:25][NH:24][C:5]2=[N:6][CH:7]=1
Reactant: NN
Reactant: CN(C)c1ccc(CC(=O)c2cc(Br)cnc2F)cc1
Solvent: CCO
Solvent: O
Product: CN(C)c1ccc(Cc2n[nH]c3ncc(Br)cc23)cc1
Temperature: 25 °C
Reaction time: 18 h
Yield: 57.2 %

Procedure:
1-(5-Bromo-2-fluoro-pyridin-3-yl)-2-(4-dimethylamino-phenyl)-ethanone (890 mg, 2.64 mmol), ethanol (100 ml), and anhydrous hydrazine (0.4 ml, 12.74 mmol) were combined and stirred for 18 hours at room temperature. The reaction was diluted with water and the precipitate filtered and dried to obtain 500 mg (57%) of [4-(5-bromo-1H-pyrazolo[3,4-b]pyridin-3-ylmethyl)-phenyl]-dimethyl-amine. MS m/z 331.1+333.1 (M+H+).
Reaction SMILES: [C:1](Cl)(=[O:13])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12].[Br-:15].[NH2:16][C:17]1[CH:42]=[C:41]([C:43]([O:45][CH3:46])=[O:44])[CH:40]=[CH:39][C:18]=1[CH2:19][P+:20]([C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>CN(C)C=O>[Br-:15].[CH3:46][O:45][C:43]([C:41]1[CH:40]=[CH:39][C:18]([CH2:19][P+:20]([C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=2)([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[C:17]([NH:16][C:1](=[O:13])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12])[CH:42]=1)=[O:44]
Reactant: COC(=O)c1ccc(C[P+](c2ccccc2)(c2ccccc2)c2ccccc2)c(N)c1
Reactant: CCCCCCCCCCCC(=O)Cl
Agent: [Br-]
Solvent: CN(C)C=O
Product: CCCCCCCCCCCC(=O)Nc1cc(C(=O)OC)ccc1C[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Reaction time: 3 h
Yield: 73.5 %

Procedure:
n-Dodecanoyl chloride (9.9 g) was added dropwise to a stirred suspension of (2-amino-4-methoxycarbonylbenzyl)triphenylphosphonium bromide (22.9 g) in dry dimethylformamide (225 ml) and stirring continued for 3 hours. The resulting solution was evaporated in vacuo to give an orangebrown oil which on treatment with water gave a solid. The solid was collected, washed with water, dried, washed with diethyl ether and collected to give [4-methoxycarbonyl-2-(n-dodecanamido)benzyl]triphenylphosphonium bromide (22.9 g) in the form of a pale yellow solid, m.p. 142°-145° C.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[C:13]([C:14]([O:16][CH3:17])=[O:15])=[C:12]([CH3:18])[O:11][N:10]=1.C(O[CH:24](N(C)C)[N:25]([CH3:27])[CH3:26])(C)(C)C>C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[C:13]([C:14]([O:16][CH3:17])=[O:15])=[C:12]([CH:18]=[CH:24][N:25]([CH3:27])[CH3:26])[O:11][N:10]=1
Reactant: CN(C)C(OC(C)(C)C)N(C)C
Reactant: COC(=O)c1c(-c2c(F)cccc2Cl)noc1C
Solvent: Cc1ccccc1
Product: COC(=O)c1c(-c2c(F)cccc2Cl)noc1C=CN(C)C

Procedure:
To a solution of 0.1 g (0.3708 mmol) methyl 3-(2-chloro-6-fluorophenyl)-5-methylisoxazole-4-carboxylate in 10 mL dry toluene, 0.15 mL (0.7417 mmol) tert-Butoxy-bis(dimethylamino)methane (Bredereck's reagent) were added. The reaction mixture was heated under reflux for 6 h.