Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]([F:29])([F:28])[C:3]1[CH:4]=[C:5]([CH2:13][O:14][CH:15]2[CH2:19][CH2:18][CH:17]([NH:20][CH3:21])[CH:16]2[C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.CCN(C(C)C)C(C)C.[C:39](Cl)(=[O:41])[CH3:40]>C(Cl)Cl>[F:1][C:2]([F:28])([F:29])[C:3]1[CH:4]=[C:5]([CH2:13][O:14][CH:15]2[CH2:19][CH2:18][CH:17]([N:20]([C:39](=[O:41])[CH3:40])[CH3:21])[CH:16]2[C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=2)[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1
Reactant: CNC1CCC(OCc2cc(C(F)(F)F)cc(C(F)(F)F)c2)C1c1ccccc1
Reactant: CC(=O)Cl
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CC(=O)N(C)C1CCC(OCc2cc(C(F)(F)F)cc(C(F)(F)F)c2)C1c1ccccc1
Yield: 90.9 %

Procedure:
To a solution of 25 mg of amine prepared in Example 11 and 0.05 mL of DIPEA in 0.5 mL of methylene chloride was added 7 mg of acetyl chloride. After 1.5 h in a sealed vial, the volatiles were evaporated under a stream of nitrogen and the residue was purified on a 1 mm preparative silica gel plate eluted with ethyl acetate to afford 25 mg of title compound. Mass spec (NH3 /CI): 460 (M+1).
Reaction SMILES: F[C:2](F)(F)[C:3](O)=[O:4].[Cl:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[N:15]1[CH:19]([C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([C:26]3[CH2:27][CH2:28][NH:29][CH2:30][CH:31]=3)[CH:21]=2)[CH2:18][C:17]([C:32]([C:38]([F:41])([F:40])[F:39])([C:34]([F:37])([F:36])[F:35])[OH:33])=[N:16]1.C(Cl)(=O)C.C(N(CC)CC)C>ClCCl>[C:3]([N:29]1[CH2:28][CH:27]=[C:26]([C:22]2[CH:21]=[C:20]([CH:19]3[N:15]([C:10]4[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=4[Cl:8])[N:16]=[C:17]([C:32]([C:38]([F:41])([F:39])[F:40])([C:34]([F:35])([F:36])[F:37])[OH:33])[CH2:18]3)[CH:25]=[CH:24][CH:23]=2)[CH2:31][CH2:30]1)(=[O:4])[CH3:2]
Reactant: O=C(O)C(F)(F)F
Reactant: OC(C1=NN(c2ccccc2Cl)C(c2cccc(C3=CCNCC3)c2)C1)(C(F)(F)F)C(F)(F)F
Solvent: ClCCl
Solvent: CCN(CC)CC
Solvent: CC(=O)Cl
Product: CC(=O)N1CC=C(c2cccc(C3CC(C(O)(C(F)(F)F)C(F)(F)F)=NN3c3ccccc3Cl)c2)CC1
Temperature: 25 °C
Reaction time: 1 h
Yield: 27.5 %

Procedure:
1-(2-Chloro-phenyl)-5-[3-(1,2,3,6-tetrahydropyridin-4-yl)-phenyl]-3-[di-(trifluoromethyl)-hydroxy-methyl]-4,5-dihydro-1H-pyrazole trifluoroacetate (11.0 mg, 0.02 mmol) prepared in Example 230, acetyl chloride (1.5 uL, 0.02 mmol), and triethylamine (7.5 uL, 0.05 mmol) were added to dichloromethane (0.5 mL). The reaction mixture was stirred at room temperature for 1 hour, washed with distilled water and brine, dried on anhydrous magnesium sulfate, and then concentrated under reduced pressure to give a yellow liquid residue. The resulting residue was purified by silica gel column chromatography (eluent: ethyl acetate/n-hexane=1/1) to give 3.0 mg of the titled compound as a yellow liquid.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:10]=[C:11]([CH:15]([NH:25][C:26](=[O:32])[O:27][C:28]([CH3:31])([CH3:30])[CH3:29])S(C2C=CC=CC=2)(=O)=O)[CH:12]=[N:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:33]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])(=[O:39])[CH2:34][C:35]([O:37][CH3:38])=[O:36].C(=O)([O-])[O-].[Cs+].[Cs+].FC(F)(F)C1C=C(NC(N[C@@H]2CCCC[C@H]2N(C)C)=S)C=C(C(F)(F)F)C=1>O.C(OCC)(=O)C.C1(C)C=CC=CC=1>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([C@@H:15]([NH:25][C:26]([O:27][C:28]([CH3:29])([CH3:30])[CH3:31])=[O:32])[CH:34]([C:35]([O:37][CH3:38])=[O:36])[C:33]([O:40][C:41]([CH3:44])([CH3:42])[CH3:43])=[O:39])[CH:12]=[N:13][CH:14]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CC(C)(C)OC(=O)NC(c1cncc(OCc2ccccc2)c1)S(=O)(=O)c1ccccc1
Reactant: COC(=O)CC(=O)OC(C)(C)C
Agent: CN(C)[C@@H]1CCCC[C@H]1NC(=S)Nc1cc(C(F)(F)F)cc(C(F)(F)F)c1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: O
Solvent: Cc1ccccc1
Solvent: CCOC(C)=O
Product: COC(=O)C(C(=O)OC(C)(C)C)[C@H](NC(=O)OC(C)(C)C)c1cncc(OCc2ccccc2)c1
Temperature: 0 °C
Reaction time: 48 h

Procedure:
Tert-butyl {[5-(benzyloxy)pyridin-3-yl](phenylsulfonyl)methyl}carbamate (2.2 g, 4.84 mmol) was suspended in a toluene (16.5 mL) water (13 mL) mixture. At 0° C. tert-butyl methyl malonate (1.0 mL, 5.8 mmol), cesium carbonate (1.58 g, 4.84 mmol) and 1-[3,5-bis(trifluoromethy)phenyl]-3-[(1R,2R)-(−)-2-(dimethylamino)cyclohexyl]thiourea (200 mg, 0.48 mmol) was added and the mixture was stirred for 48 hours at 0° C. After storage at 5° C. for 72 hours the mixture was diluted with water and ethyl acetate, the phases were separated and the aqueous phase extracted with ethyl acetate. The combined extracts were dried over sodium sulfate and concentrated. The residue was purified by chromatography on silica gel (ethyl acetate in hexane 0% to 60%) to yield 1.54 g of enantiomerically enriched tert-butyl methyl 2-{(1S)-[5-(benzyloxy)pyridin-3-yl][(tert-butoxycarbonyl)amino]methyl}propanedioate.
Reaction SMILES: [Si:1]([O:8][C:9]([CH3:36])([CH3:35])[C@H:10]([N:20]1[C:32]2[C:31]3[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=3[N:25]=[CH:24][C:23]=2[N:22]=[C:21]1[CH2:33]Cl)[CH2:11][O:12][Si](C(C)(C)C)(C)C)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[F-].C([N+](CCCC)(CCCC)CCCC)CCC.C([O-])(O)=O.[Na+]>C(Cl)Cl>[Si:1]([O:8][C:9]([C@@H:10]1[N:20]2[C:32]3[C:31]4[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=4)[N:25]=[CH:24][C:23]=3[N:22]=[C:21]2[CH2:33][O:12][CH2:11]1)([CH3:35])[CH3:36])([C:4]([CH3:6])([CH3:7])[CH3:5])([CH3:3])[CH3:2]
Reactant: CC(C)(O[Si](C)(C)C(C)(C)C)[C@@H](CO[Si](C)(C)C(C)(C)C)n1c(CCl)nc2cnc3ccccc3c21
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: O=C([O-])O
Agent: [F-]
Solvent: ClCCl
Product: CC(C)(O[Si](C)(C)C(C)(C)C)[C@H]1COCc2nc3cnc4ccccc4c3n21
Temperature: -78 °C
Reaction time: 48 h
Yield: 90.2 %

Procedure:
1-[(1R)-2-{[tert-Butyl(dimethyl)silyl]oxy}-1-({[tert-butyl(dimethyl)silyl]oxy}methyl)-2-methylpropyl]-2-(chloromethyl)-1H-imidazo[4,5-c]quinoline (1.74 g, 3.18 mmol) was dissolved in 80 mL of CH2Cl2 and the solution was cooled to −78° C. under N2. Tetrabutylammonium fluoride (1.0 M solution in THF, 3.50 mL) was added slowly and the stirred reaction mixture was allowed to warm to ambient temperature overnight. The reaction mixture was then treated with an additional 0.3 mL of tetrabutylammonium fluoride solution and stirring was continued for 2 days. The reaction mixture was then treated with saturated NaHCO3 solution, and the layers were separated. The organic portion was washed with brine (4×20 mL), dried over Na2SO4, filtered and concentrated under reduced pressure. Chromatography (SiO2, 2-5% MeOH/CHCl3) gave (11R)-11-(1-{[tert-butyl(dimethyl)silyl]oxy}-1-methylethyl)-10,11-dihydro-8H-[1,4]oxazino[4′,3′:1,2]imidazo[4,5-c]quinoline (1.14 g) as a yellow syrup.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([C:12]2[CH:17]=[C:16]([C:18]([F:21])([F:20])[F:19])[NH:15][C:14](=O)[N:13]=2)[CH:5]=[CH:6][C:7]=1[C:8]([F:11])([F:10])[F:9].P(Cl)(Cl)([Cl:25])=O>>[Cl:25][C:14]1[N:13]=[C:12]([C:4]2[CH:5]=[CH:6][C:7]([C:8]([F:11])([F:10])[F:9])=[C:2]([F:1])[CH:3]=2)[CH:17]=[C:16]([C:18]([F:21])([F:20])[F:19])[N:15]=1
Reactant: O=P(Cl)(Cl)Cl
Reactant: O=c1nc(-c2ccc(C(F)(F)F)c(F)c2)cc(C(F)(F)F)[nH]1
Product: Fc1cc(-c2cc(C(F)(F)F)nc(Cl)n2)ccc1C(F)(F)F

Procedure:
The title compound was prepared from 4-(3-fluoro-4-trifluoromethyl-phenyl)-6-trifluoromethyl-1H-pyrimidin-2-one (4.08 g, 12.5 mmol) and phosphoryl chloride (40 mL) according to the general procedure I. Obtained as a yellow solid (4.26 g, 99%). MS (EI) 344.0 [(M)+]; mp 41° C.
Reaction SMILES: [CH2:1]([O:13][C:14]1[CH:15]=[N:16][C:17]([C:20]2[CH:28]=[CH:27][C:23]([C:24](O)=[O:25])=[CH:22][CH:21]=2)=[N:18][CH:19]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12].S(Cl)([Cl:31])=O>>[CH2:1]([O:13][C:14]1[CH:15]=[N:16][C:17]([C:20]2[CH:28]=[CH:27][C:23]([C:24]([Cl:31])=[O:25])=[CH:22][CH:21]=2)=[N:18][CH:19]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12]
Reactant: O=S(Cl)Cl
Reactant: CCCCCCCCCCCCOc1cnc(-c2ccc(C(=O)O)cc2)nc1
Product: CCCCCCCCCCCCOc1cnc(-c2ccc(C(=O)Cl)cc2)nc1

Procedure:
4-(5-n-Dodecyloxypyrimidine-2-yl)benzoic acid (3.0 g) together with excess thionyl chloride were heated for 6 hours under refluxing and thereafter, unaltered thionyl chloride was distilled off to obtain 4-(5-n-dodecyloxypyrimidine-2-yl)phenylcarboxylic acid chloride.
Reaction SMILES: Br[CH2:2][C:3]([O:5][CH3:6])=[O:4].[C:7]1([CH2:13][CH2:14][CH2:15][CH2:16][P:17]([O:21]CC)[O:18][CH2:19][CH3:20])[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1>>[CH2:19]([O:18][P:17]([CH2:2][C:3]([O:5][CH3:6])=[O:4])([CH2:16][CH2:15][CH2:14][CH2:13][C:7]1[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=1)=[O:21])[CH3:20]
Reactant: CCOP(CCCCc1ccccc1)OCC
Reactant: COC(=O)CBr
Product: CCOP(=O)(CCCCc1ccccc1)CC(=O)OC
Reaction time: 0.75 h

Procedure:
A mixture of 16.9 g. (0.11 mole) of methyl bromoacetate and 5.0 g. (0.019 mole) of (4-phenylbutyl)phosphonous acid, diethyl ester was heated on a 140°-150° oil bath until distillation of ethyl bromide was detected. An additional 16 g. (0.063 mole) of (4-phenylbutyl)phosphonous acid, diethyl ester was then gradually added to the reaction mixture. Heating was then continued for 45 minutes. After cooling to 100°, excess reagent was removed in vacuo to give 25 g. of crude product (Rf =0.25 silica gel/ethyl acetate). Impurities with higher Rf values were separated by flash chromatography using ethyl acetate. As a result, 18.3 g. of [ethoxy(4-phenylbutyl)phosphinyl]acetic acid, methyl ester were obtained.
Reaction SMILES: [S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[SH:6].C(=O)([O-])[O-].[K+].[K+].Cl[CH2:14][C:15](=[O:26])[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH3:25]>CC(C)=O>[S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[S:6][CH2:14][C:15](=[O:26])[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH3:25]
Reactant: Sc1cccs1
Reactant: CCCCCCCCCCC(=O)CCl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: CCCCCCCCCCC(=O)CSc1cccs1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 71.3 %

Procedure:
To a solution of thiophene-2-thiol (2.0 g, 17.2 mmol) in dry acetone (100 ml) is added anhydrous potassium carbonate (2.8 g; 20 mmol), followed by 1-chlorododecan-2-one (3.8 g, 17.2 mmol) dropwise. The reaction is stirred for 30 min and RT, filtered and concentrated under reduced pressure. The crude product is further purified by column chromatography (eluent: petrol/ethyl acetate 100:0 to 95:5) to afford the product as a colourless oil (3.66 g, 71%). M/Z 298 (M+). 1H NMR (300 MHz, CDCl3) δ 7.36 (1H, dd), 7.15 (1H, dd), 6.96 (1H, dd), 3.55 (2H, s), 2.55 (2H, t), 1.57 (2H, m), 1.35-1.20 (14H, m), 0.88 (3H, t). 13C NMR (75 MHz, CDCl3) δ 205.1, 134.6, 132.5, 130.3, 127.7, 48.2, 41.1, 31.9, 29.6, 29.5, 29.4, 29.3, 29.1, 23.8, 22.7, 14.1.
Reaction SMILES: Cl[CH2:2][C:3]1[CH:4]=[CH:5][C:6]([C:9]2[S:17][C:16]3[C:11](=[N:12][CH:13]=[CH:14][C:15]=3[O:18][C:19]3[CH:24]=[CH:23][C:22]([N+:25]([O-:27])=[O:26])=[CH:21][C:20]=3[F:28])[CH:10]=2)=[N:7][CH:8]=1.[NH2:29][CH2:30][CH2:31][CH2:32][C:33]([O:35]CC)=O.CCN(C(C)C)C(C)C>C(#N)C>[F:28][C:20]1[CH:21]=[C:22]([N+:25]([O-:27])=[O:26])[CH:23]=[CH:24][C:19]=1[O:18][C:15]1[CH:14]=[CH:13][N:12]=[C:11]2[CH:10]=[C:9]([C:6]3[N:7]=[CH:8][C:3]([CH2:2][N:29]4[CH2:30][CH2:31][CH2:32][C:33]4=[O:35])=[CH:4][CH:5]=3)[S:17][C:16]=12
Reactant: O=[N+]([O-])c1ccc(Oc2ccnc3cc(-c4ccc(CCl)cn4)sc23)c(F)c1
Reactant: CCOC(=O)CCCN
Solvent: CC#N
Solvent: CCN(C(C)C)C(C)C
Product: O=C1CCCN1Cc1ccc(-c2cc3nccc(Oc4ccc([N+](=O)[O-])cc4F)c3s2)nc1
Temperature: 25 °C
Yield: 48.3 %

Procedure:
A mixture of 102 (500 mg, 1.202 mmol), ethyl 4-aminobutanoate (403 mg, 2.405 mmol) and DIPEA (0.630 mL, 3.61 mmol) under nitrogen in acetonitrile (12 mL) was heated to reflux for 3 days, then cooled to RT. The reaction mixture was then concentrated. The crude product was purified by Biotage (25M column; MeOH/DCM: 0/100 to 20/80 over 20 CV). The desired fractions were collected, concentrated and dried under high vacuum to afford the title compound 103 (270 mg, 0.58 mmol, 48% yield). MS (m/z): 465.5 (M+H).
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[C:10]([NH2:11])=[CH:9][C:8]([C:12]([F:15])([F:14])[F:13])=[C:7](Br)[N:6]=1)=[O:4].[Cl:17][C:18]1[CH:23]=[C:22]([Cl:24])[CH:21]=[CH:20][C:19]=1B(O)O.P([O-])([O-])([O-])=O.[K+].[K+].[K+].CCOC(C)=O>C1(C)C=CC=CC=1.O>[CH3:1][O:2][C:3]([C:5]1[C:10]([NH2:11])=[CH:9][C:8]([C:12]([F:15])([F:14])[F:13])=[C:7]([C:21]2[CH:20]=[CH:19][C:18]([Cl:17])=[CH:23][C:22]=2[Cl:24])[N:6]=1)=[O:4]
Reactant: OB(O)c1ccc(Cl)cc1Cl
Reactant: COC(=O)c1nc(Br)c(C(F)(F)F)cc1N
Agent: O=P([O-])([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CCOC(C)=O
Solvent: Cc1ccccc1
Product: COC(=O)c1nc(-c2ccc(Cl)cc2Cl)c(C(F)(F)F)cc1N
Temperature: 110 °C
Reaction time: 3 h

Procedure:
3-Amino-6-bromo-5-trifluoromethyl-pyridine-2-carboxylic acid methyl ester (Intermediate A4) (3 g, 10.03 mmol), 2,4-dichlorophenylboronic acid (2.297 g, 12.04 mmol), potassium phosphate (4.26 g, 20.06 mmol) and Fibrecat® 1034A (Johnson Matthey, polymer supported palladium complex) (500 mg, 10.03 mmol) were suspended in toluene (50 ml) and water (15 ml). The reaction mixture was heated to 110° C. under vigorous stirring for 3 hours. The mixture was allowed to cool to RT and EtOAc (100 ml) was added. The organic layer was separated and washed with brine (15 ml). MP-TMT (macroporous polystyrene-bound trimercaptotriazine, 3 g, Polymern labs) was added and stirred for 1 hour at RT. MgSO4 was added and the suspension filtered off. The filtrate was concentrated in vacuo and purification of the residue by reverse phase chromatography (130 g C18 column) eluting with water/MeOH afforded the title compound as a white solid; LS-MS Rt=1.55 mins [M+H]+ 365 (Method 2minLC_v002).
Reaction SMILES: FC(F)(F)C(O)=O.[CH3:8][CH:9]([O:13][C:14]1[N:22]=[C:21]2[C:17]([N:18]=[C:19]([O:23][CH3:24])[NH:20]2)=[C:16]([NH2:25])[N:15]=1)[CH2:10][O:11][CH3:12].C(=O)([O-])[O-].[K+].[K+].CS(O[CH2:37][CH:38]1[CH2:43][CH2:42][CH2:41][O:40][CH2:39]1)(=O)=O>CN(C)C=O.C(OCC)(=O)C>[CH3:8][CH:9]([O:13][C:14]1[N:22]=[C:21]2[C:17]([N:18]=[C:19]([O:23][CH3:24])[N:20]2[CH2:37][CH:38]2[CH2:43][CH2:42][CH2:41][O:40][CH2:39]2)=[C:16]([NH2:25])[N:15]=1)[CH2:10][O:11][CH3:12]
Reactant: COCC(C)Oc1nc(N)c2nc(OC)[nH]c2n1
Reactant: CS(=O)(=O)OCC1CCCOC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O=C(O)C(F)(F)F
Solvent: CCOC(C)=O
Product: COCC(C)Oc1nc(N)c2nc(OC)n(CC3CCCOC3)c2n1
Temperature: 60 °C
Reaction time: 1.5 h
Yield: 62.7 %

Procedure:
To a solution of 2-{[1-methyl-2-(methoxy)ethyl]oxy}-8-(methoxy)-9H-purin-6-amine trifluoroacetic acid salt (500 mg) in dry N,N-dimethylformamide (6.0 ml) at room temperature and under nitrogen was added potassium carbonate (0.75 g) in one go. The reaction was stirred at 60° C. for 1.5 hours. A solution of tetrahydro-2H-pyran-3-ylmethyl methanesulfonate (0.29 g) in dry N,N-dimethylformamide (1.0 ml) was added in one go and the reaction heated at 90° C. for 2 hours. The reaction was cooled to room temperature and then diluted with ethyl acetate (20 ml) and washed with water (10 ml). The organic layer was concentrated in vacuo. The product was purified by C18 reverse phase chromatography using water (containing 0.1% formic acid)-acetonitrile (containing 0.05% formic acid) as eluant (10-60%) to afford the title compound as a clear viscous oil (300 mg).
Reaction SMILES: [NH2:1][C:2]1[C:7]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[C:6]([CH3:13])[N:5]=[C:4]2[S:14][C:15]([CH3:17])=[CH:16][C:3]=12.[Br:18]N1C(=O)CCC1=O>C(Cl)Cl>[NH2:1][C:2]1[C:7]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[C:6]([CH3:13])[N:5]=[C:4]2[S:14][C:15]([CH3:17])=[C:16]([Br:18])[C:3]=12
Reactant: O=C1CCC(=O)N1Br
Reactant: CCOC(=O)c1c(C)nc2sc(C)cc2c1N
Solvent: ClCCl
Product: CCOC(=O)c1c(C)nc2sc(C)c(Br)c2c1N
Reaction time: 1 h
Yield: 111.6 %

Procedure:
To a stirred solution of ethyl 4-amino-2,6-dimethylthieno[2,3-b]pyridine-5-carboxylate (6.44 g, 25.7 mmol) (Description 5) in DCM (110 mL), was added N-bromosuccinimide (9.16 g, 51.5 mmol) and the resulting mixture was stirred for 1 h. The mixture was concentrated and the solid that precipitated was filtered and washed with DCM (3×10 mL), to afford the title compound (9.44 g). LCMS (A) m/z: 329/331 [M+1]+, Rt 1.22 min (acidic).
Reaction SMILES: C(NC1C=CC(C2C=C3C(CN([C@@H](C(C)C)C(O)=O)C3=O)=CC=2)=CC=1)(=O)C1C=CC=CC=1.[CH3:33][CH:34]([CH3:73])[C@H:35]([N:40]1[CH2:48][C:47]2[C:42](=[CH:43][C:44]([C:49]3[CH:54]=[CH:53][C:52]([NH:55][C:56]([C:58]4[CH:67]=[CH:66][C:65]5[C:64]([CH3:69])([CH3:68])[CH2:63][CH2:62][C:61]([CH3:71])([CH3:70])[C:60]=5[CH:59]=4)=[O:57])=[CH:51][CH:50]=3)=[CH:45][CH:46]=2)[C:41]1=[O:72])[C:36]([O:38]C)=[O:37]>>[CH3:33][CH:34]([CH3:73])[C@H:35]([N:40]1[CH2:48][C:47]2[C:42](=[CH:43][C:44]([C:49]3[CH:50]=[CH:51][C:52]([NH:55][C:56]([C:58]4[CH:67]=[CH:66][C:65]5[C:64]([CH3:69])([CH3:68])[CH2:63][CH2:62][C:61]([CH3:71])([CH3:70])[C:60]=5[CH:59]=4)=[O:57])=[CH:53][CH:54]=3)=[CH:45][CH:46]=2)[C:41]1=[O:72])[C:36]([OH:38])=[O:37]
Reactant: COC(=O)[C@H](C(C)C)N1Cc2ccc(-c3ccc(NC(=O)c4ccc5c(c4)C(C)(C)CCC5(C)C)cc3)cc2C1=O
Agent: CC(C)[C@@H](C(=O)O)N1Cc2ccc(-c3ccc(NC(=O)c4ccccc4)cc3)cc2C1=O
Product: CC(C)[C@@H](C(=O)O)N1Cc2ccc(-c3ccc(NC(=O)c4ccc5c(c4)C(C)(C)CCC5(C)C)cc3)cc2C1=O
Yield: 77 %

Procedure:
The compound of example 176 was prepared analogous to compound of example 98 by hydrolysis of compound of example 175.
Reaction SMILES: [I:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([CH:8]=[C:9]([C:11]3[CH:18]=[CH:17][C:14]([C:15]#N)=[CH:13][CH:12]=3)[N:10]=2)[CH:7]=1.[H-].C([Al+]CC(C)C)C(C)C.[Cl-].[NH4+].S([O-])([O-])(=O)=[O:32].[Mg+2]>C(OCC)C.ClCCl.O1CCCC1>[I:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([CH:8]=[C:9]([C:11]3[CH:18]=[CH:17][C:14]([CH:15]=[O:32])=[CH:13][CH:12]=3)[N:10]=2)[CH:7]=1
Reactant: O=S(=O)([O-])[O-]
Reactant: N#Cc1ccc(-c2cn3cc(I)ccc3n2)cc1
Agent: CC(C)C[Al+]CC(C)C
Agent: [Cl-]
Agent: [H-]
Solvent: CCOCC
Solvent: C1CCOC1
Solvent: ClCCl
Product: O=Cc1ccc(-c2cn3cc(I)ccc3n2)cc1
Reaction time: 4 h

Procedure:
4-(6-Iodoimidazo[1,2-a]pyridin-2-yl)benzonitrile (1.27 g) was added to a mixture of tetrahydrofuran (15 mL) and dichloromethane (15 mL), followed by stirring under ice cooling. Diisobutylaluminum hydride (7.8 mL) was added dropwise to the reaction mixture, and the resultant mixture was stirred at the same temperature for 15 minutes and then at room temperature for 4 hours. Aqueous saturated ammonium chloride solution (2 mL) was added dropwise to the reaction mixture, followed by stirring at room temperature for 1 hour. Subsequently, magnesium sulfate and diethyl ether were added to the reaction mixture, followed by further stirring for 1 hour. The solvent was evaporated, and the residue was purified through silica gel column chromatography (dichloromethane:methanol=95:5). The purified product was concentrated under reduced pressure, to thereby yield the title compound (1.03 g).
Reaction SMILES: [C:1]1([CH:8]=[CH:7][CH:6]=[C:4]([OH:5])[CH:3]=1)[OH:2].[C:9]([O:12][CH2:13][CH2:14][CH:15]([CH2:17][CH2:18][CH:19]=[C:20]([CH3:22])[CH3:21])[CH3:16])(=[O:11])[CH3:10].C1(C)C=CC(S(O)(=O)=O)=CC=1>CCOCC>[C:9]([O:12][CH2:13][CH2:14][CH:15]([CH3:16])[CH2:17][CH2:18][CH2:19][C:20]([C:6]1[CH:7]=[CH:8][C:1]([OH:2])=[CH:3][C:4]=1[OH:5])([CH3:22])[CH3:21])(=[O:11])[CH3:10]
Reactant: Oc1cccc(O)c1
Reactant: CC(=O)OCCC(C)CCC=C(C)C
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: CCOCC
Product: CC(=O)OCCC(C)CCCC(C)(C)c1ccc(O)cc1O

Procedure:
11.0 Parts of resorcinol, 10.0 parts of citronellyl acetate and 0.5 parts of p-toluene sulphonic acid are heated at 115° C. for 45 hours. The reaction mixture is then taken up in ether, washed with sodium bicarbonate solution, water, and evaporated. The residual oil is distilled and yields 3.9 parts of 7-(2',4'-dihydroxyphenyl)-3,7-dimethyloct-1-yl acetate b0.2 215° C. with the following percentage composition by weight:
Reaction SMILES: CC1C=CC(S(O[CH2:12][CH:13]2[CH2:22][CH2:21][C:20]3[C:15](=[CH:16][C:17]([S:23]([CH3:26])(=[O:25])=[O:24])=[CH:18][CH:19]=3)[O:14]2)(=O)=O)=CC=1.[CH2:27]([NH:29][CH2:30][CH3:31])[CH3:28]>C(#N)C>[CH2:27]([N:29]([CH2:12][CH:13]1[CH2:22][CH2:21][C:20]2[C:15](=[CH:16][C:17]([S:23]([CH3:26])(=[O:24])=[O:25])=[CH:18][CH:19]=2)[O:14]1)[CH2:30][CH3:31])[CH3:28]
Reactant: Cc1ccc(S(=O)(=O)OCC2CCc3ccc(S(C)(=O)=O)cc3O2)cc1
Reactant: CCNCC
Solvent: CC#N
Product: CCN(CC)CC1CCc2ccc(S(C)(=O)=O)cc2O1

Procedure:
Preparation according to Example 25: [7-(methylsulfonyl)-3,4-dihydro-2H-chromen-2-yl]methyl 4-methylbenzenesulfonate (0.020 g, 0.0504 mmol), N-ethylethanamine (0.5 ml), ACN (3 ml). MS m/z (rel. intensity, 70 eV) 297 (M+, 1), 131 (4), 87 (6), 86 (bp), 58 (5), 56 (3).
Reaction SMILES: [H-].[Na+].[O:3]1[CH:7]=[CH:6][CH:5]=[C:4]1[C:8]1[N:16]=[C:15]2[N:10]([C:11]([NH2:20])=[N:12][C:13]3[NH:19][CH:18]=[CH:17][C:14]=32)[N:9]=1.Cl[CH2:22][CH2:23][N:24]1[CH2:29][CH2:28][N:27]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=2[O:36][CH3:37])[CH2:26][CH2:25]1.O>CN(C=O)C>[O:3]1[CH:7]=[CH:6][CH:5]=[C:4]1[C:8]1[N:16]=[C:15]2[N:10]([C:11]([NH2:20])=[N:12][C:13]3[N:19]([CH2:22][CH2:23][N:24]4[CH2:25][CH2:26][N:27]([C:30]5[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=5[O:36][CH3:37])[CH2:28][CH2:29]4)[CH:18]=[CH:17][C:14]=32)[N:9]=1
Reactant: COc1ccccc1N1CCN(CCCl)CC1
Reactant: Nc1nc2[nH]ccc2c2nc(-c3ccco3)nn12
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: COc1ccccc1N1CCN(CCn2ccc3c2nc(N)n2nc(-c4ccco4)nc32)CC1
Temperature: 0 °C
Reaction time: 0.25 h

Procedure:
To a suspension of NaH (13 mg, 0.32 mmol) in anhydrous DMF (2 mL) at 0° C. is added slowly a solution of the title B compound, 2-(furan-2-yl)-7H-pyrrolo[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine (60 mg, 0.25 mmol) in 2 mL of anhydrous DMF. After stirring at 0° C. under N2 for 15 min, 1-(2-chloroethyl)-4-(2-methoxyphenyl)piperazine (0.275 mmol) is added at 0° C. The mixture is warmed to RT and stirred overnight. The reaction mixture is then poured into water and extracted with DCM (3×). The organic layer is dried over anhydrous MgSO4, filtered and concentrated in vacuo. The crude product is purified by flash chromatography using DCM/MeOH/NH4OH (98/2/0 2) as eluent to give 2-(furan-2-yl)-7-(2-(4-(2-methoxyphenyl)piperazin-1-yl)ethyl)-7H-pyrrolo[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine: LC/MS (M+1=459.2). 1H NMR (DMSO-d6, 400 MHz) δ 2.56 (m, 4H), 2.67 (t, 2H, J=6.0 Hz), 2.94 (m, 4H), 3.76 (s, 3H), 4.28 (t, 2H, J=6.0 Hz), 6.60 (d, 1H, J=3.2 Hz), 6.71 (m, 1H), 6.85 (m, 2H), 6.92 (m, 2H), 7.18 (m, 2H), 7.49 (brs, NH2), 7.91 (d, 1H, J=1.6 Hz).
Reaction SMILES: N([C@@H]1[C@@H:11]([OH:12])[C@H:10](O)[C@@H:9]([CH2:14]O)[O:8][C@H]1SC)=[N+]=[N-].C([O:19][C:20](=[O:22])[CH3:21])(=O)C>N1C=CC=CC=1>[CH3:14][C:9]([CH2:10][C:11]([CH2:21][C:20]([OH:19])=[O:22])=[O:12])=[O:8]
Reactant: CC(=O)OC(C)=O
Reactant: CS[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1N=[N+]=[N-]
Solvent: c1ccncc1
Product: CC(=O)CC(=O)CC(=O)O
Reaction time: 1 h

Procedure:
To methyl 2-azido-2-deoxy-1-thio-β-D-glucopyranoside. (10 g, 42.50 mmol) in pyridine (50 mL) at 0° C. was added acetic anhydride (20 g) and the reaction stirred for 1 hour. The reaction mixture was evaporated to dryness and the residue extracted to give the title triacetate (15.23 g, quantitative,), Rf=0.7 (CHCl3/Petroleum ethers, 1:1).