Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N:1]1[C:9]([NH:10][C@H:11]([C:13]2[N:17]([CH:18]3[CH2:23][CH2:22][N:21](C(OC(C)(C)C)=O)[CH2:20][CH2:19]3)[C:16]3[CH:31]=[CH:32][CH:33]=[CH:34][C:15]=3[N:14]=2)[CH3:12])=[C:8]2[C:4]([NH:5][CH:6]=[N:7]2)=[N:3][CH:2]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH:21]1[CH2:22][CH2:23][CH:18]([N:17]2[C:16]3[CH:31]=[CH:32][CH:33]=[CH:34][C:15]=3[N:14]=[C:13]2[C@@H:11]([NH:10][C:9]2[N:1]=[CH:2][N:3]=[C:4]3[C:8]=2[N:7]=[CH:6][NH:5]3)[CH3:12])[CH2:19][CH2:20]1
Reactant: C[C@H](Nc1ncnc2[nH]cnc12)c1nc2ccccc2n1C1CCN(C(=O)OC(C)(C)C)CC1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: C[C@H](Nc1ncnc2[nH]cnc12)c1nc2ccccc2n1C1CCNCC1
Temperature: 25 °C
Reaction time: 2 h
Yield: 86.1 %

Procedure:
To a solution of 4-{2-[(S)-1-(9H-purin-6-ylamino)ethyl]benzoimidazol-1-yl}piperidine-1-carboxylic acid tertbutyl ester 112 (101 mg, 0.218 mmol) in DCM (3 mL) was added TFA (1 mL) and the mixture was stirred at RT for 2 h. The reaction mixture was loaded onto an Isolute® SCX-2 cartridge which was washed with MeOH and the product eluted with 2M NH3/MeOH. The product containing fractions were combined and concentrated under reduced pressure. The resulting residue was purified by column chromatography (Si—PCC, gradient 0-20% 2M NH3/MeOH in DCM) affording 113 as a white solid (68 mg, 86%). LCMS: RT 1.65 min [M+H]+ 363.1. 1H NMR (CDCl3, 400 MHz): δ 8.34 (1H, s), 7.88 (1H, s), 7.75-7.65 (3H, m), 7.27-7.19 (3H, m), 6.01 (1H, br), 4.80-4.70 (1H, m), 3.39-3.38 (1H, m), 3.37-3.30 (1H, m), 3.19-3.09 (1H, m), 2.89-2.38 (3H, m) 1.99-1.70 (6H, m)
Reaction SMILES: [NH2:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[C@@H:11]2[CH2:15][C@H:14]([CH2:16][OH:17])[CH:13]=[CH:12]2)=[C:4](Cl)[N:3]=1.[CH2:19]1[CH:23]([CH2:24][OH:25])[CH2:22][CH:21]([NH2:26])[CH2:20]1.[OH-].[Na+]>C(N(CC)CC)C.C(O)C>[NH2:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[C@@H:11]2[CH2:15][C@H:14]([CH2:16][OH:17])[CH:13]=[CH:12]2)=[C:4]([NH:26][C@H:21]2[CH2:20][CH2:19][C@@H:23]([CH2:24][OH:25])[CH2:22]2)[N:3]=1
Reactant: NC1CCC(CO)C1
Reactant: Nc1nc(Cl)c2ncn([C@H]3C=C[C@@H](CO)C3)c2n1
Agent: [Na+]
Agent: [OH-]
Solvent: CCN(CC)CC
Solvent: CCO
Product: Nc1nc(N[C@H]2CC[C@@H](CO)C2)c2ncn([C@H]3C=C[C@@H](CO)C3)c2n1
Temperature: 25 °C

Procedure:
A solution of (±)-cis-4-(2-Amino-6-chloro-9H-purin-9-yl)-2-cyclopentene-1-methanol (530 mg, 2.00 mmol) from Example 4, 3-aminocyclopentyl-1-methanol (276 mg, 24 mmol), triethylamine (1.12 g, 10.98 mmol), and ethanol (20 mL) was stirred at reflux for 5 hours. An additional amount of triethylamine (1.17 g) was then added and the solution was refluxed for 8 additional hours. The solution was allowed to cool to room temperature and 2 mL of 1 N NaOH was added. The solution was concentrated and the residues were placed on silica gel column which was eluted with 10% methanol-chloroform (0.36 g, 52%). Recrystallization of such a sample from ethanolacetonitrile gave title compound as white powder, m.p. 177-180° C.
Reaction SMILES: Br[C:2]1[CH:11]=[C:10]2[C:5]([C:6]([C:13]3[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=3)=[CH:7][C:8](=[O:12])[O:9]2)=[CH:4][CH:3]=1.[F:20][C:21]([F:35])([F:34])[C@:22]([OH:33])([C:27]1[S:31][C:30]([SH:32])=[N:29][CH:28]=1)[CH2:23][C:24]([OH:26])=[O:25].C(=O)([O-])[O-].[K+].[K+]>CN1C(=O)CCC1>[F:35][C:21]([F:20])([F:34])[C@@:22]([C:27]1[S:31][C:30]([S:32][C:2]2[CH:11]=[C:10]3[C:5]([C:6]([C:13]4[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=4)=[CH:7][C:8](=[O:12])[O:9]3)=[CH:4][CH:3]=2)=[N:29][CH:28]=1)([OH:33])[CH2:23][C:24]([OH:26])=[O:25]
Reactant: O=c1cc(-c2ccc(F)cc2)c2ccc(Br)cc2o1
Reactant: O=C(O)C[C@@](O)(c1cnc(S)s1)C(F)(F)F
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN1CCCC1=O
Product: O=C(O)C[C@@](O)(c1cnc(Sc2ccc3c(-c4ccc(F)cc4)cc(=O)oc3c2)s1)C(F)(F)F

Procedure:
Employing the procedure of Example 1, Step 3, using 7-bromo-4-(4-fluorophenyl)-2H-chromen-2-one (0.467 g, 1.5 mmol), (3S)-4,4,4-trifluoro-3-hydroxy-3-(2-mercapto-1,3-thiazol-5-yl)butanoic acid (enantiomer #1, 0.400 g, 1.5 mmol) and potassium carbonate (0.708 g, 5.1 mmol) in NMP at 120° C., the title compound was obtained. Purification was done on silica gel (CH2Cl2/MeOH/HOAc; 90:10:0.5). [α]25D−30° (c=0.5, CHCl3). 1H NMR (400 MHz, acetone-d6): δ 7.99 (s, 1H), 7.68 (m, 2H), 7.58 (m, 2H), 7.48 (dd, 1H), 7.39 (dd, 2H), 6.43 (s, 1H), 3.33 (dd, 2H).
Reaction SMILES: C(OCC)(=O)CC(C)=O.[CH2:10]([N:17]1[CH2:22][CH2:21][CH:20]([NH:23][NH2:24])[CH2:19][CH2:18]1)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.[CH:25]1([C:28]2N(C(C)C)N=[CH:30][C:29]=2[CH:36]=[O:37])CC1.C(N1CCC(=O)CC1)C1C=CC=CC=1.CN1CCC(NN)CC1>>[CH2:10]([N:17]1[CH2:18][CH2:19][CH:20]([N:23]2[C:28]([CH3:25])=[C:29]([CH:36]=[O:37])[CH:30]=[N:24]2)[CH2:21][CH2:22]1)[C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1.[CH2:10]([N:17]1[CH2:18][CH2:19][CH:20]([NH:23][NH2:24])[CH2:21][CH2:22]1)[C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1
Reactant: CC(C)n1ncc(C=O)c1C1CC1
Agent: CN1CCC(NN)CC1
Agent: NNC1CCN(Cc2ccccc2)CC1
Agent: O=C1CCN(Cc2ccccc2)CC1
Solvent: CCOC(=O)CC(C)=O
Product: Cc1c(C=O)cnn1C1CCN(Cc2ccccc2)CC1

Procedure:
1-(1-Benzyl-piperidin-4-yl)-5-methyl-1H-pyrazole-4-carbaldehyde was prepared from ethyl acetoacetate and (1-benzyl-piperidin-4-yl)-hydrazine in the same manner as 5-cyclopropyl-1-isopropyl-1H-pyrazole-4-carbaldehyde (Example 49). (1-Benzyl-piperidin-4-yl)-hydrazine was prepared from 1-benzyl-piperidin-4-one in the same manner as (1-methyl-piperidin-4-yl)-hydrazine (Example 92).
Reaction SMILES: Cl.[CH3:2][NH:3][O:4][CH3:5].C[Al](C)C.[N:10]1([CH:16]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:17]([O:19]C)=O)[CH2:15][CH2:14][O:13][CH2:12][CH2:11]1.Cl>>[CH3:5][O:4][N:3]([CH3:2])[C:17](=[O:19])[CH:16]([N:10]1[CH2:11][CH2:12][O:13][CH2:14][CH2:15]1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1
Reactant: COC(=O)C(c1ccccc1)N1CCOCC1
Reactant: CNOC
Agent: C[Al](C)C
Agent: Cl
Product: CON(C)C(=O)C(c1ccccc1)N1CCOCC1
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
N,O-Dimethylhydroxylamine hydrochloride (1.66 g, 17.0 mmol) was suspended in 20 mL of dry TVF and cooled to 0° C. Trimethylaluminum (8.50 mL, 2.0M solution in toluene, 17.0 mmol) was added slowly and stirred for 30 minutes. Methyl morpholin-4-yl-(phenyl)acetate (1.00 g, 4.25 mmol) was added to the cooled mixture in an 8 mL TIFF solution. The reaction was allowed to warm to ambient temperature while for 18 hours. The mixture was poured into 1N HCl(aq) and stirred for 1 hour. The mixture was then poured into NaHCO3(sat) and extracted 3× with EtOAc. The combined organic layers were washed 1× with brine, dried with Na2SO4, filtered and concentrated in vacuo to provide N-methoxy-N-methyl-2-morpholin-4-yl-2-phenylacetamide. HRMS [M+H] C14H21N2O3 calc'd 265.1547. found 265.1553.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([S:8](Cl)(=[O:10])=[O:9])=[CH:4][CH:3]=1.[CH3:12][CH:13]([OH:15])[CH3:14].O>N1C=CC=CC=1>[CH:13]([O:15][S:8]([C:5]1[CH:6]=[CH:7][C:2]([CH3:1])=[CH:3][CH:4]=1)(=[O:10])=[O:9])([CH3:14])[CH3:12]
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Reactant: CC(C)O
Solvent: c1ccncc1
Solvent: O
Product: Cc1ccc(S(=O)(=O)OC(C)C)cc1
Temperature: 0 °C
Reaction time: 2 h

Procedure:
At 0° C., 4-methyl-benzenesulfonyl chloride (3.8 g) was added to a solution of 2-propanol (6.12 ml) in pyridine (6.6 ml). The reaction mixture was stirred at 0° C. for 2 h and then at 20° C. for 16 h. The reaction mixture was poured into water (150 ml) and extracted with dichloromethane. The combined organic phases were washed with 3M aqueous HCl and sat. NaHCO3. After drying (MgSO4) and concentrating in vacuo, the title product was obtained as a pale yellow oil. Yield: 2.89 g. MS-ESI: [M+H]+=215.
Reaction SMILES: [C:1]1([C:7]#[C:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.O>C(OCC)(=O)C>[C:1]1([CH2:7][CH2:8][C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: C(#Cc1ccccc1)c1ccccc1
Solvent: CCOC(C)=O
Solvent: O
Product: c1ccc(CCc2ccccc2)cc1
Reaction time: 0.5 h
Yield: 98 %

Procedure:
89.1 mg (0.50 mmol) of diphenylacetylene (1), 270 μL (15 mmol) of distilled water and stainless steel balls (50 pieces) were placed in the vessel of the planetary ball mill, which was then closed, and agitated by operating the planetary ball mill for 12 hours at 800 rpm (reversed every 30 minutes). After the lapse of 12 hours, 10 mL of ethyl acetate was added to the vessel of the ball mill to provide a solution containing the reaction mixture, which was then filtered with celite. The operation was repeated 5 times to provide a filtrate, which was then concentrated, thereby providing 89.4 mg (0.49 mmol) of 1,2-diphenylethane (2). The yield was 98%.
Reaction SMILES: N[C@@H:2]([C:4]([OH:6])=[O:5])[CH3:3].C(N[C@@H](C(O)=O)C)(=O)CC[CH2:10][CH2:11][C@H:12]1[C@@H:20]2[C@@H:15]([NH:16][C:17]([NH:19]2)=[O:18])[CH2:14][S:13]1.Cl.CN(C)CCCN=C=NCC.ON1C(=O)CCC1=O.[CH2:48]1[N:59]([CH2:60][C:61]([OH:63])=[O:62])[CH2:58][CH2:57][N:56]([CH2:64][C:65]([OH:67])=[O:66])[CH2:55][CH2:54][N:53]([CH2:68][C:69]([OH:71])=[O:70])[CH2:52][CH2:51][N:50]([CH2:72][C:73]([OH:75])=[O:74])[CH2:49]1.NC1C=CC=CC=1>>[CH2:49]1[N:50]([CH2:72][C:73]([OH:75])=[O:74])[CH2:51][CH2:52][N:53]([CH2:68][C:69]([OH:71])=[O:70])[CH2:54][CH2:55][N:56]([CH2:64][C:65]([OH:67])=[O:66])[CH2:57][CH2:58][N:59]([CH2:60][C:61]([OH:63])=[O:62])[CH2:48]1.[OH:6][C:4]([CH2:2][CH2:3][CH2:10][CH2:11][C@H:12]1[C@@H:20]2[C@@H:15]([NH:16][C:17]([NH:19]2)=[O:18])[CH2:14][S:13]1)=[O:5]
Reactant: C[C@@H](N)C(=O)O
Reactant: C[C@@H](NC(=O)CCCC[C@@H]1SC[C@@H]2NC(=O)N[C@@H]21)C(=O)O
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: O=C(O)CN1CCN(CC(=O)O)CCN(CC(=O)O)CCN(CC(=O)O)CC1
Solvent: Nc1ccccc1
Product: O=C(O)CCCC[C@@H]1SC[C@@H]2NC(=O)N[C@@H]21

Procedure:
The D-alanine-linked conjugate was prepared by first coupling D-alanine (Sigma Chemical Co.) to biotin-NHS ester. The resultant biotinyl-D-alanine was then activated with 1-(3-dimethylaminopropyl)-3-ethyl-carbodiimide hydrochloride (EDCI) and N-hydroxysuccinimide (NHS). This NHS ester was reacted in situ with DOTA-aniline to give the desired product which was purified by preparative HPLC.
Reaction SMILES: Cl.[NH2:2][OH:3].[H-].[Na+].[CH2:6]([N:13]1[C:17](=[O:18])[CH:16]2[CH:19]([CH3:31])[N:20]([CH3:30])[CH:21]([C:22]3[CH:29]=[CH:28][C:25]([C:26]#[N:27])=[CH:24][CH:23]=3)[CH:15]2[C:14]1=[O:32])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1>CN(C=O)C>[NH2:27][C:26](=[N:2][OH:3])[C:25]1[CH:28]=[CH:29][C:22]([CH:21]2[N:20]([CH3:30])[CH:19]([CH3:31])[CH:16]3[C:17](=[O:18])[N:13]([CH2:6][C:7]4[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=4)[C:14](=[O:32])[CH:15]23)=[CH:23][CH:24]=1
Reactant: NO
Reactant: CC1C2C(=O)N(Cc3ccccc3)C(=O)C2C(c2ccc(C#N)cc2)N1C
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CC1C2C(=O)N(Cc3ccccc3)C(=O)C2C(c2ccc(C(N)=NO)cc2)N1C
Temperature: 0 °C
Reaction time: 120 h
Yield: 48.2 %

Procedure:
841 mg (12.12 mmol) of hydroxylamine hydrochloride were suspended in 4 ml of DMF and cooled to 0° C. 303 mg (10.1 mmol) of 80% sodium hydride were added slowly. 365 mg (1.01 mmol) of (1RS,3SR,3aRS,6aSR)-4-(5-benzyl-2,3-dimethyl-4,6-dioxo-octahydro-pyrrolo[3,4-c]pyrrol-1-yl)-benzonitrile were dissolved in DMF and added to the reaction mixture. The cooling was thereafter no longer renewed. The mixture was stirred at room temperature for 5 days. Thereafter, it was filtered and the solvent was removed in a high vacuum. The mixture was purified chromatographically (RP18, gradient from water to methanol). 191 mg (48%) of (3aRS,4SR,6RS,6aSR)-4-[4-(amino-hydroxyimino-methyl)-phenyl]-2-benzyl-5,6-dimethyl-tetrahydro-pyrrolo[3,4-c]pyrrole-1,3-dione were isolated as a colourless powder. M.p.: 194°-196° C. ISP-MS: 393 ([M+H]+, 100); 303 (20); 219 (10).
Reaction SMILES: [OH:1][CH2:2][C:3]1[C:8]([F:9])=[CH:7][N:6]=[C:5]([F:10])[C:4]=1[F:11].[Cl:12][C:13]([C:23]([F:26])([F:25])[F:24])=[CH:14][C@@H:15]1[C@H:17]([C:18](Cl)=[O:19])[C:16]1([CH3:22])[CH3:21]>>[Cl:12][C:13]([C:23]([F:24])([F:25])[F:26])=[CH:14][C@@H:15]1[C@H:17]([C:18]([O:1][CH2:2][C:3]2[C:8]([F:9])=[CH:7][N:6]=[C:5]([F:10])[C:4]=2[F:11])=[O:19])[C:16]1([CH3:22])[CH3:21]
Reactant: OCc1c(F)cnc(F)c1F
Reactant: CC1(C)[C@H](C=C(Cl)C(F)(F)F)[C@@H]1C(=O)Cl
Product: CC1(C)[C@H](C=C(Cl)C(F)(F)F)[C@@H]1C(=O)OCc1c(F)cnc(F)c1F
Yield: 45.1 %

Procedure:
By the method of Example 2, 0.3 g (0.002 mole) of 4-hydroxymethyl-2,3,5-trifluoropyridine (from Example 9) was reacted with 0.5 g (0.002 mole) of cis-3-(2-chloro-3,3,3-trifluoropropenyl)-2,2-dimethylcyclopropanecarbonyl chloride to produce 0.35 g of (2,3,5-trifluoropyridin-4-yl)methyl cis-3-(2-chloro-3,3,3-trifluoropropenyl)-2,2-dimethylcyclopropanecarboxylate as a clear, yellow oil, Compound 15 of the tables below.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6]([C:8]([O:10]C)=O)[CH:5]=[C:4](N[C@@H](C)C(OC)=O)[N:3]=1.CO.[NH3:21]>>[Cl:1][C:2]1[N:7]=[C:6]([C:8]([NH2:21])=[O:10])[CH:5]=[CH:4][N:3]=1
Reactant: N
Reactant: COC(=O)c1cc(N[C@@H](C)C(=O)OC)nc(Cl)n1
Solvent: CO
Product: NC(=O)c1ccnc(Cl)n1
Yield: 89 %

Procedure:
A solution of the (S)-methyl 2-chloro-6-((1-methoxy-1-oxopropan-2-yl)amino)pyrimidine-4-carboxylate (3.719 g, 13.59 mmol) in 7M ammonia in methanol (20 mL, 140 mmol) was heated in a sealed tube for 3 days at 50° C. After cooling, the precipitated solid was filtered off and rinsed with MeOH (2×5 mL) then dried under vacuum at 40° C. to give (S)-6-(1-amino-1-oxopropan-2-yl)amino)-2-chloropyrimidine-4-carboxamide as a pale yellow powder (2.946 g, 12.09 mmol, 89% yield). LC/MS: m/z=244.2 [M+H]+.
Reaction SMILES: [NH2:1][C@@H:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][NH:10][C:11]2[N:16]=[CH:15][CH:14]=[CH:13][N:12]=2)[CH2:4][C@H:3]1[OH:17].ClC(Cl)Cl.[F:22][C:23]([F:34])([F:33])[C:24]1[CH:25]=[C:26]([CH:30]=[CH:31][CH:32]=1)[C:27](Cl)=[O:28]>C(N(CC)CC)C>[OH:17][C@H:3]1[C@H:2]([NH:1][C:27](=[O:28])[C:26]2[CH:30]=[CH:31][CH:32]=[C:24]([C:23]([F:22])([F:33])[F:34])[CH:25]=2)[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][NH:10][C:11]2[N:12]=[CH:13][CH:14]=[CH:15][N:16]=2)[CH2:4]1
Reactant: O=C(Cl)c1cccc(C(F)(F)F)c1
Reactant: N[C@@H]1CCN(CCNc2ncccn2)C[C@H]1O
Solvent: CCN(CC)CC
Solvent: ClC(Cl)Cl
Product: O=C(N[C@@H]1CCN(CCNc2ncccn2)C[C@H]1O)c1cccc(C(F)(F)F)c1
Reaction time: 0.25 h
Yield: 50.5 %

Procedure:
To a stirred solution of 2.37 parts of trans-4-amino-1-[2-(2-pyrimidinylamino)ethyl]-3-piperidinol in 120 parts of trichloromethane were added 2.08 parts of 3-(trifluoromethyl)benzoyl chloride. The whole was stirred for 15 minutes in an ice bath. After the addition of 1.26 parts of N,N-diethylethanamine, stirring was continued for 18 hours and the temperature was allowed to reach room temperature. The reaction mixture was washed with a sodium carbonate solution and water, dried, filtered and evaporated. The residue was purified by column chromatography over silica gel using a mixture of trichloromethane and methanol, saturated with ammonia, (95:5 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was suspended in 2,2'-oxybispropane. The product was filtered off and dried, yielding 2.07 parts (50.5%) of trans-N-[3-hydroxy-1-[2-(2-pyrimidinylamino)ethyl]-4-piperidinyl]-3-(trifluoromethyl)benzamide; mp. 148.3° C. (compound 65).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([NH:11][C@H:12]([CH2:17][OH:18])[C@@H:13]([CH3:16])[CH2:14][CH3:15])(=[O:10])=[O:9])=[CH:4][CH:3]=1.[C:19](=O)([O-])[O-].[K+].[K+].IC>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([S:8]([N:11]([CH3:19])[C@H:12]([CH2:17][OH:18])[C@@H:13]([CH3:16])[CH2:14][CH3:15])(=[O:9])=[O:10])=[CH:6][CH:7]=1
Reactant: O=C([O-])[O-]
Reactant: CC[C@H](C)[C@@H](CO)NS(=O)(=O)c1ccc(Cl)cc1
Agent: [K+]
Solvent: CI
Solvent: CN(C)C=O
Product: CC[C@H](C)[C@@H](CO)N(C)S(=O)(=O)c1ccc(Cl)cc1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 67.7 %

Procedure:
To a solution of 4-chloro-N-[(1S,2S)-1-(hydroxymethyl)-2-methylbutyl]benzenesulfonamide (0.10 g, 0.343 mmol) dissolved in DMF (2.0 mL) was added potassium carbonate (47 mg, 0.343 mmol). After 30 minutes, the reaction mixture was cooled to 0° C. and iodomethane (50 μL, 0.686 mmol) was added. After 2 hours, the ice bath was removed and the reaction mixture was stirred at 25° C. for 24 hours. The insolubles were then filtered off and the DMF solution was diluted with EtOAc (50 mL) and washed sequentially with 10% citric acid (50 mL) and saturated brine (50 mL), dried over MgSO4 and evaporated to a clear oil which was washed with Et2O and then purified by flash chromatography (eluant: 95-5 CHCl3/iPrOH) to afford the desired product as a clear oil (71 mg, 68%). Mass Spectrum (+APCI): 306 ([M+H]+). Anal: Calc'd for C13H20ClNO3S: C, 51.06; H, 6.59; N, 4.58. Found: C, 51.15; H, 6.73; N, 4.36.
Reaction SMILES: [CH:1](OCC#N)=[O:2].Cl.[CH3:8][O:9][C:10](=[O:20])[C@H:11]([CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[NH2:12].C(N(CC)CC)C>ClCCl>[CH:1]([NH:12][CH:11]([CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[C:10]([O:9][CH3:8])=[O:20])=[O:2]
Reactant: N#CCOC=O
Reactant: COC(=O)[C@@H](N)Cc1ccccc1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COC(=O)C(Cc1ccccc1)NC=O
Temperature: 0 °C
Reaction time: 16 h

Procedure:
Cyanomethyl formate (Aldrich, Order No. 453579, 5.05 g, 59.3 mmole) was suspended together with the phenylalanine methyl ester hydrochloride (Aldrich, Order No. 525472, 12.80 g, 59.3 mmole) in 80 ml dichloromethane and cooled to 0° C. in an ice bath. Triethylamine (6.01 g, 59.3 mmole) dissolved in 15 ml of dichloromethane was then added and the mixture was stirred for 16 hours at room temperature. A clear solution formed. In order to work up the mixture the latter was diluted with 100 ml of dichloromethane and washed firstly with 200 ml of saturated NaHCO3 solution and then twice with saturated NaCl solution. The organic phase was dried over magnesium sulfate and concentrated by evaporation. The product obtained was used without further purification for the next stage.
Reaction SMILES: [CH3:1][C:2]1[N:6]2[C:7](=[S:11])[NH:8][N:9]=[CH:10][C:5]2=[C:4]([CH3:12])[N:3]=1.[CH2:13](I)[CH3:14].C1C2N(C=NC=2)C(=S)NN=1.CI>>[CH3:1][C:2]1[N:6]2[C:7]([S:11][CH2:13][CH3:14])=[N:8][N:9]=[CH:10][C:5]2=[C:4]([CH3:12])[N:3]=1
Reactant: Cc1nc(C)n2c(=S)[nH]ncc12
Reactant: CCI
Agent: S=c1[nH]ncc2cncn12
Solvent: CI
Product: CCSc1nncc2c(C)nc(C)n12

Procedure:
The procedure of Example 29 is repeated substituting equimolecular amounts of 6,8-dimethyl-imidazo[1,5-d]-as-triazine-4(3H)-thione and ethyl iodide for the imidazo[1,5-d]-as-triazine-4(3H)-thione and methyl iodide employed in that example. There is thus obtained the title compound in equally good yield.
Reaction SMILES: [OH:1][CH2:2][C:3]1([CH2:15][OH:16])[CH2:9][CH2:8][CH2:7][C:6]2[CH:10]=[CH:11][CH:12]=[CH:13][C:5]=2[C:4]1=[O:14].C(N(CC)CC)C.[F:24][C:25]1[CH:30]=[C:29]([F:31])[CH:28]=[CH:27][C:26]=1[N:32]=[C:33]=[S:34]>O1CCCC1>[OH:16][CH2:15][C:3]1([CH2:2][O:1][C:33](=[S:34])[NH:32][C:26]2[CH:27]=[CH:28][C:29]([F:31])=[CH:30][C:25]=2[F:24])[CH2:9][CH2:8][CH2:7][C:6]2[CH:10]=[CH:11][CH:12]=[CH:13][C:5]=2[C:4]1=[O:14]
Reactant: O=C1c2ccccc2CCCC1(CO)CO
Reactant: Fc1ccc(N=C=S)c(F)c1
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: O=C1c2ccccc2CCCC1(CO)COC(=S)Nc1ccc(F)cc1F

Procedure:
To a solution of 6,6-bis(hydroxymethyl)-6,7,8,9-tetrahydrobenzocyclohepten-5-one (500 mg, 2.27 mmol) in 28 ml of tetrahydrofuran were added, at room temperature, triethylamine (0.35 ml, 2.50 mmol) and 2,4-difluorophenyl isothiocyanate (740 μl, 5.68 mmol). The mixture was heated to reflux for 72 hours, concentrated and purified by column chromatography on silica gel (eluent: 1:2 tert-butyl methyl ether/cyclohexane). The product was obtained in a yield of 234 mg (26%).
Reaction SMILES: [C:1]1([C:7]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[CH:8][CH3:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1.[Br:34]N1C(=O)CCC1=O>C(Cl)(Cl)(Cl)Cl>[Br:34][CH2:9][CH:8]=[C:7]([C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1)[C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: CC=C(c1ccccc1)c1ccccc1
Reactant: O=C1CCC(=O)N1Br
Agent: O=C(OOC(=O)c1ccccc1)c1ccccc1
Solvent: ClC(Cl)(Cl)Cl
Product: BrCC=C(c1ccccc1)c1ccccc1
Temperature: 25 °C

Procedure:
A mixture of 1,1-diphenyl-1-propene (17.0 g, 0.10 mol), carbon tetrachloride (100 ml), benzoylperoxide (0.2 g) and N-bromosuccinimide (17.8 g, 0.10 mol) was heated at reflux temperature for 18 h. The reaction mixture was allowed to cool to room temperature, filtered and the solvent was evaporated in vacuo to give 3-bromo-1 1-diphenyl-1-propene in a quantitative yield.
Reaction SMILES: [C:1]([O:5][C:6]([C:8]1[O:9][C:10]2[CH:17]=[CH:16][CH:15]=[C:14]([OH:18])[C:11]=2[C:12]=1[CH3:13])=[O:7])([CH3:4])([CH3:3])[CH3:2].[Br:19]N1C(=O)CCC1=O>C(Cl)(Cl)(Cl)Cl>[C:1]([O:5][C:6]([C:8]1[O:9][C:10]2[CH:17]=[CH:16][C:15]([Br:19])=[C:14]([OH:18])[C:11]=2[C:12]=1[CH3:13])=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: Cc1c(C(=O)OC(C)(C)C)oc2cccc(O)c12
Reactant: O=C1CCC(=O)N1Br
Solvent: ClC(Cl)(Cl)Cl
Product: Cc1c(C(=O)OC(C)(C)C)oc2ccc(Br)c(O)c12
Temperature: 0 °C
Reaction time: 6 h
Yield: 85 %

Procedure:
To 200 mg (0.81 mmol) of 4-hydroxy-3-methyl-benzofuran-2-carboxylic acid tert-butyl ester was added 2 mL of carbon tetrachloride. The mixture was cooled with water/ice bath while 1 equivalent of N-bromosuccinimide was added in small portions. After stirring at 0° C. for 6 h, the reaction mixture was filtered and the filtrate was loaded onto a column and purified by column chromatography to give 225 mg (85% yield) of 5-bromo-4-hydroxy-3-methyl-benzofuran-2-carboxylic acid tert-butyl ester as a white solid.
Reaction SMILES: [OH-].[Na+].[Cl:3][C:4]1[CH:5]=[C:6]2[C:12]3=[CH:13][C:14]4[C:22](=[CH:23][C:11]3=[N:10][C:7]2=[CH:8][CH:9]=1)[C:21]1[C:16](=[CH:17][CH:18]=[C:19]([Cl:24])[CH:20]=1)[N:15]=4.Br[CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH3:37].CO>[Cl-].C([N+](CC)(CC)CC)C1C=CC=CC=1.CS(C)=O>[Cl:24][C:19]1[CH:20]=[C:21]2[C:22]3=[CH:23][C:11]4[N:10]([CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH3:37])[C:7]5[C:6]([C:12]=4[CH:13]=[C:14]3[N:15]([CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:11][CH2:12][CH2:6][CH2:5][CH2:4][CH2:9][CH3:8])[C:16]2=[CH:17][CH:18]=1)=[CH:5][C:4]([Cl:3])=[CH:9][CH:8]=5
Reactant: Clc1ccc2c(c1)-c1cc3c(cc1=N2)-c1cc(Cl)ccc1N=3
Reactant: CCCCCCCCCCCCBr
Agent: CC[N+](CC)(CC)Cc1ccccc1
Agent: [Cl-]
Agent: [Na+]
Solvent: CS(C)=O
Solvent: CO
Product: CCCCCCCCCCCCn1c2ccc(Cl)cc2c2cc3c(cc21)c1cc(Cl)ccc1n3CCCCCCCCCCCC
Reaction time: 4 h
Yield: 175.3 %

Procedure:
50% aqueous NaOH solution (4 mL) was added to a well-stirred mixture of 2,8-dichloroindolo[3,2-b]carbazole (0.65 g, 2 mmol) as prepared above, benzyltriethylammonium chloride (90 mg, 0.4 mmol), and 1-bromododecane (1.99 g, 8 mmol) in DMSO (20 mL) in a 100-mL flask, and the resultant mixture was stirred at room temperature for 1 h and then at 50° C. for 4 h. Subsequently, the mixture was poured into MeOH (200 mL), and the precipitated yellow solid was filtered and washed 3 times each with water, N,N-dimethylformamide, methanol, and acetone, yielding 1.16 g (88.0%) of 2,8-dichloro-5,11-didodecylindolo[3,2-b]carbazole, compound (3), after drying in vacuo. It was then subject to train sublimation to obtain electrically pure samples for OTFT fabrication.
Reaction SMILES: [Br:1][C:2]1[C:3]([N:10]=[N:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[C:4]([NH2:9])[C:5]([Br:8])=[CH:6][CH:7]=1.C(O)(=O)C.C(O)(=O)C.IC1C=CC=CC=1.C(O)(=O)C>O>[Br:1][C:2]1[C:3]2[C:4](=[N:9][N:11]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[N:10]=2)[C:5]([Br:8])=[CH:6][CH:7]=1
Reactant: Nc1c(Br)ccc(Br)c1N=Nc1ccccc1
Solvent: Ic1ccccc1
Solvent: O
Solvent: CC(=O)O
Product: Brc1ccc(Br)c2nn(-c3ccccc3)nc12
Temperature: 25 °C
Reaction time: 1 h
Yield: 50 %

Procedure:
The 3,6-dibromo-2-phenylazo-phenylamine (120 mg, 0.34 mmol), iodobenzene diacetate (109 mg, 0.34 mmol), and acetic acid (5 mL) were added to a 1-neck 100-mL round bottom flask. The solution was stirred for 1 h at room temperature. The solvent was reduced with a rotary evaporator and the flask was stored at −19° C. for 16 h resulting in the formation of a solid cake. Water was added to the solid cake to dissolve the acid. A crystalline solid was collected by filtration and washed with water. GC/MS confirmed the solid as the desired product. Yield: 50%.