Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[S:9]([CH:12]1[CH2:16][C@@H:15]([C:17]([OH:19])=O)[C@H:14]([CH2:20][O:21][C:22]2[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=2)[CH2:13]1)(=[O:11])=[O:10].[NH2:29][C:30]1([C:33]#[N:34])[CH2:32][CH2:31]1>>[C:33]([C:30]1([NH:29][C:17]([C@@H:15]2[CH2:16][CH:12]([S:9]([C:3]3[CH:4]=[CH:5][C:6]([F:8])=[CH:7][C:2]=3[Cl:1])(=[O:11])=[O:10])[CH2:13][C@H:14]2[CH2:20][O:21][C:22]2[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=2)=[O:19])[CH2:32][CH2:31]1)#[N:34]
Reactant: O=C(O)[C@@H]1CC(S(=O)(=O)c2ccc(F)cc2Cl)C[C@H]1COc1ccc(F)cc1
Reactant: N#CC1(N)CC1
Product: N#CC1(NC(=O)[C@@H]2CC(S(=O)(=O)c3ccc(F)cc3Cl)C[C@H]2COc2ccc(F)cc2)CC1

Procedure:
The title compound was prepared in analogy to example 68 step 11 using (1R,2R)-4-(2-Chloro-4-fluoro-benzenesulfonyl)-2-(4-fluoro-phenoxymethyl)-cyclopentanecarboxylic acid (epimeric mixture, example 143 and 144 step 6) and 1-aminocyclopropanecarbonitrile. Light orange oil (51%). MS (EI): 493.4 (M−H)−.
Reaction SMILES: C([N:8](CC1C=CC=CC=1)[C:9]1([CH2:13][NH:14][C:15]2[C:24]3[C:19](=[CH:20][CH:21]=[C:22]([CH3:25])[CH:23]=3)[N:18]=[C:17]([N:26]3[CH2:32][C:31]4[CH:33]=[C:34]([N:37]5[CH2:42][CH2:41][O:40][CH2:39][CH2:38]5)[CH:35]=[CH:36][C:30]=4[S:29](=[O:44])(=[O:43])[CH2:28][CH2:27]3)[CH:16]=2)[CH2:12][O:11][CH2:10]1)C1C=CC=CC=1.FC(F)(F)C(O)=O.C(=O)(O)[O-].[Na+]>CO.[OH-].[Pd+2].[OH-]>[NH2:8][C:9]1([CH2:13][NH:14][C:15]2[C:24]3[C:19](=[CH:20][CH:21]=[C:22]([CH3:25])[CH:23]=3)[N:18]=[C:17]([N:26]3[CH2:32][C:31]4[CH:33]=[C:34]([N:37]5[CH2:42][CH2:41][O:40][CH2:39][CH2:38]5)[CH:35]=[CH:36][C:30]=4[S:29](=[O:43])(=[O:44])[CH2:28][CH2:27]3)[CH:16]=2)[CH2:10][O:11][CH2:12]1
Reactant: Cc1ccc2nc(N3CCS(=O)(=O)c4ccc(N5CCOCC5)cc4C3)cc(NCC3(N(Cc4ccccc4)Cc4ccccc4)COC3)c2c1
Agent: [Pd+2]
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CO
Solvent: O=C(O)C(F)(F)F
Product: Cc1ccc2nc(N3CCS(=O)(=O)c4ccc(N5CCOCC5)cc4C3)cc(NCC3(N)COC3)c2c1
Reaction time: 12 h
Yield: 40.9 %

Procedure:
A mixture of N-{[3-(dibenzylamino)oxetan-3-yl]methyl}-6-methyl-2-[7-(morpholin-4-yl)-1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl]quinolin-4-amine (100 mg, 0.14 mmol), 10% palladium hydroxide on active carbon (100 mg) and trifluoroacetic acid (0.5 mL) in methanol (20 mL) was stirred for 12 hours under hydrogen (1 bar). Then the mixture was basified with a saturated aqueous solution of sodium bicarbonate, and extracted with dichloromethane. The organic layer was dried over anhydrous sodium sulfate, and concentrated in vacuo. The residue was purified by preparative HPLC to afford 30 mg of the product (yield was 40%). MS obsd. (ESI+) [(M+H)+] 524, 1HNMR ((400 MHz, CD3OD) δ ppm 7.72-7.60 (m, 2 H), 7.56 (d, J=2.27 Hz, 1 H), 7.33 (d, J=8.34 Hz, 1 H), 7.25 (dd, J=8.46, 1.39 Hz, 1 H), 6.85 (dd, J=8.84, 2.53 Hz, 1 H), 6.30-6.03 (m, 2 H), 5.00 (brs, 2 H), 4.53-4.31 (m, 4 H), 3.86-3.68 (m, 4 H), 3.51 (d, J=14.40 Hz, 4 H), 3.33-3.19 (m, 6 H), 2.41 (brs, 1 H), 2.37 (s, 3 H).
Reaction SMILES: P(Cl)(Cl)(Cl)(Cl)Cl.[O:7]1[CH:11]=[CH:10][CH:9]=[C:8]1[C:12](=[N:16][O:17][CH3:18])[C:13]([OH:15])=O.[NH2:19][C@@H:20]1[C:39](=[O:40])[N:22]2[C:23]([C:36]([OH:38])=[O:37])=[C:24]([CH2:27][O:28][C:29](=[O:35])[NH:30]C(=O)CCl)[CH2:25][S:26][C@H:21]12.C(N(CC)CC)C>ClCCl.CO.CN(C)C(=O)C>[C:29]([O:28][CH2:27][C:24]1[CH2:25][S:26][C@@H:21]2[C@H:20]([NH:19][C:13](=[O:15])[C:12]([C:8]3[O:7][CH:11]=[CH:10][CH:9]=3)=[N:16][O:17][CH3:18])[C:39](=[O:40])[N:22]2[C:23]=1[C:36]([OH:38])=[O:37])(=[O:35])[NH2:30]
Reactant: N[C@@H]1C(=O)N2C(C(=O)O)=C(COC(=O)NC(=O)CCl)CS[C@H]12
Reactant: CON=C(C(=O)O)c1ccco1
Agent: ClP(Cl)(Cl)(Cl)Cl
Solvent: CC(=O)N(C)C
Solvent: CO
Solvent: ClCCl
Product: CON=C(C(=O)N[C@@H]1C(=O)N2C(C(=O)O)=C(COC(N)=O)CS[C@H]12)c1ccco1
Temperature: 0 °C
Reaction time: 0.17 h
Yield: 90.3 %

Procedure:
N,N-Dimethylacetamide (1.5 ml) was added to a solution of phosphorus pentachloride (750mg, 3.6mmole) in anhydrous dichloromethane (15ml) cooled to -10°. After 10 minutes, 2-(fur-2-yl)-2-methoxyiminoacetic acid (syn isomer) (612mg, 3.6mmole) was added to the resulting suspension, which soon became a clear solution and was stirred at -10° for 15 minutes. Ice (3g) was added and after 10 minutes the layers were allowed to separate in a dropping funnel. The organic phase was slowly (over 5 minutes) run into a cooled (-10°) solution of (6R,7R)-7-amino-3-chloroacetylcarbamoyloxymethylceph-3-em-4-carboxylic acid (1.05g, 3mmole) in dichloromethane (15ml) containing triethylamine (0.9ml, 6.5mmole). Methanol (1ml) was added after 40 minutes, and 5 minutes later the reaction mixture was extracted twice with 3% w/v aqueous sodium bicarbonate solution (150ml). The aqueous extract was washed with ethyl acetate (25ml) and left at 20° for 4 hours. The solution was washed twice with ethyl acetate, acidified with 2N-hydrochloric acid, and extracted 3 times with ethyl acetate. The combined organic layers were dried over magnesium sulphate, decolourised with activated charcoal, and evaporated in vacuo to give a pale-yellow solid (1.15g, 87%). This was washed with diethyl ether and filtered off to give the title compound (0.91g,71%); λmaxpH6 274nm (ε17,300). The IR and NMR spectra of the product agreed with those of an authentic sample.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([CH2:8][CH2:9][C:10]([N:12]([CH:22]([CH3:24])[CH3:23])[NH:13][C:14](=[O:21])[C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[O:11])[CH:5]=[CH:6][CH:7]=1.C([O-])([O-])=O.[Na+].[Na+].[C:31]1(B(O)O)[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1>COCCOC>[C:2]1([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[CH:7]=[CH:6][CH:5]=[C:4]([CH2:8][CH2:9][C:10]([N:12]([CH:22]([CH3:24])[CH3:23])[NH:13][C:14](=[O:21])[C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[O:11])[CH:3]=1
Reactant: CC(C)N(NC(=O)c1ccccc1)C(=O)CCc1cccc(Br)c1
Reactant: OB(O)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: COCCOC
Product: CC(C)N(NC(=O)c1ccccc1)C(=O)CCc1cccc(-c2ccccc2)c1
Yield: 68.7 %

Procedure:
A solution of benzoic acid N′-[3-(3-bromo-phenyl)-propionyl]-N′-isopropyl-hydrazide (100 mg, 0.26 mmol) in DME (5 ml)/2M Na2CO3 (450 μL, 0.90 mmol) was treated with phenylboronic acid (47 mg, 0.39 mmol) and Pd[PPh3]4 (30 mg, 0.026 mmol) for 18 hours at 90° C. The reaction mixture was partitioned between water and ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate, filtered, and concentrated. The crude was absorbed on silica and purified on a silica gel column with a 30-50% ethyl acetate/hexanes gradient to afford the product as a solid (69 mg, 70%). LC-MS m/e 387.19 (M+H+)
Reaction SMILES: O=[CH:2][C:3]1[CH:11]=[CH:10][C:8]([OH:9])=[C:5]([O:6][CH3:7])[CH:4]=1.Cl.[NH2:13][CH2:14][CH2:15][SH:16]>C(O)C.O>[OH:9][C:8]1[CH:10]=[CH:11][C:3]([CH:2]2[NH:13][CH2:14][CH2:15][S:16]2)=[CH:4][C:5]=1[O:6][CH3:7]
Reactant: COc1cc(C=O)ccc1O
Reactant: NCCS
Agent: Cl
Solvent: O
Solvent: CCO
Product: COc1cc(C2NCCS2)ccc1O
Temperature: 25 °C
Reaction time: 16.5 h
Yield: 66.7 %

Procedure:
To a solution of vanillin (2.0 g, 13.2 mmol) in ethanol (15 ml) was added dropwise a solution of cysteamine HCl (0.5 g, 4.4 mmol) in water (5 ml) and the solution stirred at RT for 16.5 h. The bulk of the ethanol was removed by rotary evaporator and the residue was diluted with water (15 ml) and extracted with diethyl ether (3×20 ml) to remove excess aldehyde. The aqueous layer was basified by addition of solid sodium carbonate (0.3 g) causing the product to precipitate out of solution. The precipitate was filtered, washed carefully with water (3×20 ml) and dried in a vacuum desiccator to give 2-(4-hydroxy-3-methoxyphenyl)-1,3-thiazolane (7) as a white solid (0.62 g, 67%), mp 158-161° (lit mp, 182-183°). 1H nmr (d6-dmso, 300 MHz) 2.8-3.0, m, H4,4,5; 3.12, br s, NH; 3.4-3.6, m, H5; 3.76, s, OMe; 5.34, s, H2; 6.70, d (8.0 Hz), H5′; 6.84, dd (1.8, 8.1 Hz), H6′; 7.04, d (1.8 Hz), H2′; 8.91, s, OH. ESI (+ve) MS m/z 212 (M+H, 100%).
Reaction SMILES: [C:1]1([N:7]2[C:15]([NH2:16])=[C:14]3[C:9]([CH2:10][CH2:11][CH2:12][CH2:13]3)=[N:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:17]1(=O)[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(=O)C>C(Cl)Cl>[CH:17]1([NH:16][C:15]2[N:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)[N:8]=[C:9]3[C:14]=2[CH2:13][CH2:12][CH2:11][CH2:10]3)[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1
Reactant: O=C1CCCCC1
Reactant: Nc1c2c(nn1-c1ccccc1)CCCC2
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: CC(=O)O
Solvent: ClCCl
Product: c1ccc(-n2nc3c(c2NC2CCCCC2)CCCC3)cc1

Procedure:
In analogy to the procedure described in example 1.1, a mixture of 2-phenyl-4,5,6,7-tetrahydro-2H-indazol-3-ylamine (Andrew, Herbert F.; Buckley, Donald. (1963), GB 926327) and cyclohexanone ([108-94-1]) was reacted with sodium triacetoxyborohydride in the presence of acetic acid in CH2Cl2 under reflux conditions for 5 h to give the title compound as colorless oil. MS: m/e=296.4 [M+H+].
Reaction SMILES: Cl[CH2:2][C:3]1[CH:8]=[C:7]([O:9][CH3:10])[C:6]([N+:11]([O-:13])=[O:12])=[CH:5][C:4]=1[F:14].[P:15]([O:22]CC)([O:19][CH2:20][CH3:21])[O:16][CH2:17][CH3:18]>>[F:14][C:4]1[CH:5]=[C:6]([N+:11]([O-:13])=[O:12])[C:7]([O:9][CH3:10])=[CH:8][C:3]=1[CH2:2][P:15](=[O:22])([O:19][CH2:20][CH3:21])[O:16][CH2:17][CH3:18]
Reactant: CCOP(OCC)OCC
Reactant: COc1cc(CCl)c(F)cc1[N+](=O)[O-]
Product: CCOP(=O)(Cc1cc(OC)c([N+](=O)[O-])cc1F)OCC
Temperature: 100 °C
Yield: 35 %

Procedure:
A mixture of 1-(chloromethyl)-2-fluoro-5-methoxy-4-nitrobenzene (Compound 130C, 1.578 g, 7.186 mmol) and triethyl phosphite (1.43 g, 8.62 mmol) was heated at 100° C. for 16 h in a sealed tube. After concentrating the reaction mixture under reduced pressure, the crude product was purified by silica gel chromatography on an ISCO combi-flash system using DCM/MeOH as eluent (100:0→95:5) to give an orange oil, 800 mg (35% yield). 1H NMR (CDCl3, 400 MHz): δ=1.30 (t, J=7.07 Hz, 6H), 3.20-3.27 (m, 2H), 3.97 (s, 3H), 4.11 (dd, J=8.08, 7.07 Hz, 4H), 7.17 (dd, J=5.94, 2.65 Hz, 1H), 7.67 (dd, J=8.72, 0.88 Hz, 1H). MS (ES+): m/z 322.09 [MH+] (TOF, polar).
Reaction SMILES: [N:1]1([C:6]2[CH:11]=[CH:10][C:9]([CH2:12][C:13]([OH:15])=O)=[CH:8][CH:7]=2)[CH:5]=[N:4][N:3]=[N:2]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:40][CH:41]1[CH2:50][C:49]2[C:44](=[CH:45][CH:46]=[C:47]([CH2:51][CH2:52][N:53]3[CH2:58][CH2:57][NH:56][CH:55]([CH3:59])[CH2:54]3)[CH:48]=2)[C:43](=[O:60])[O:42]1.CCN(C(C)C)C(C)C>C(Cl)Cl>[CH3:40][CH:41]1[CH2:50][C:49]2[C:44](=[CH:45][CH:46]=[C:47]([CH2:51][CH2:52][N:53]3[CH2:58][CH2:57][N:56]([C:13](=[O:15])[CH2:12][C:9]4[CH:8]=[CH:7][C:6]([N:1]5[CH:5]=[N:4][N:3]=[N:2]5)=[CH:11][CH:10]=4)[CH:55]([CH3:59])[CH2:54]3)[CH:48]=2)[C:43](=[O:60])[O:42]1
Reactant: O=C(O)Cc1ccc(-n2cnnn2)cc1
Reactant: CC1CN(CCc2ccc3c(c2)CC(C)OC3=O)CCN1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: CC1Cc2cc(CCN3CCN(C(=O)Cc4ccc(-n5cnnn5)cc4)C(C)C3)ccc2C(=O)O1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A solution of [4-(1H-tetrazol-1-yl)phenyl]acetic acid (101 mg, 0.49 mmol) in DCM (1271 μl) was treated with HATU (189 mg, 0.49 mmol) at room temp. After 5 minutes a solution of of 3-methyl-6-[2-(3-methylpiperazin-1-yl)ethyl]-3,4-dihydro-1H-isochromen-1-one (110 mg, 0.38 mmol) and DIEA (167 μl, 0.954 mmol) in DCM (1271 μl) was added and the reaction allowed to stir overnight at room temp. The reaction was quenched with water and SPE purification gives crude product which was purified via reverse phase HPLC (5-85% gradient elution ACN/H2O with 0.5% TFA) to obtain 3-methyl-6-[2-(3-methyl-4-{[4-(1H-tetrazol-1-yl)phenyl]acetyl}piperazin-1-yl)ethyl]-3,4-dihydro-1H-isochromen-1-one. LC-MS (IE, m/z): 475 [M+1]+.
Reaction SMILES: [H-].[Na+].[C:3]([C:5]1[CH:10]=[CH:9][C:8]([CH2:11][CH2:12][NH:13][C:14](=O)OCC2C=CC=CC=2)=[CH:7][CH:6]=1)#[N:4].CI>O1CCCC1>[CH3:14][NH:13][CH2:12][CH2:11][C:8]1[CH:7]=[CH:6][C:5]([C:3]#[N:4])=[CH:10][CH:9]=1
Reactant: N#Cc1ccc(CCNC(=O)OCc2ccccc2)cc1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CI
Product: CNCCc1ccc(C#N)cc1
Temperature: 25 °C
Reaction time: 0.08 h

Procedure:
With ice bath cooling, 0.43 g (17.03 mmol) of sodium hydride (95%) was added to a solution of 3.183 g (11.36 mmol) of benzyl [2-(4-cyanophenyl)ethyl]carbamate in 70 ml of tetrahydrofuran. The mixture was stirred for a further 5 minutes with cooling and at room temperature for 10 minutes. 1.06 ml (17.03 mmol) of methyl iodide were then added to the reaction mixture, which was subsequently stirred at room temperature overnight. With ice bath cooling, the mixture was then quenched with water and extracted with ethyl acetate. The organic extracts were washed with saturated sodium chloride solution, dried over sodium sulphate and evaporated to dryness. The product obtained in this manner was reacted further without additional purification.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Br:8])[N:3]=1.[CH3:9][O:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2[S:18][C:19]([Sn](CCCC)(CCCC)CCCC)=[CH:20][N:21]=2)=[CH:13][CH:12]=1.C1(C)C=CC=CC=1>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>[Br:8][C:4]1[N:3]=[C:2]([C:19]2[S:18][C:17]([C:14]3[CH:15]=[CH:16][C:11]([O:10][CH3:9])=[CH:12][CH:13]=3)=[N:21][CH:20]=2)[CH:7]=[CH:6][CH:5]=1
Reactant: Brc1cccc(Br)n1
Reactant: CCCC[Sn](CCCC)(CCCC)c1cnc(-c2ccc(OC)cc2)s1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: Cc1ccccc1
Solvent: O
Product: COc1ccc(-c2ncc(-c3cccc(Br)n3)s2)cc1
Reaction time: 24 h
Yield: 59 %

Procedure:
A sealed tube was charged with 2,6-dibromopyridine (474 mg, 2.00 mmol), 2-(4-methoxyphenyl)-5-(tributylstannyl)thiazole (920 mg, 2.00 mmol), Pd(PPh3)4 (231 mg, 0.20 mmol), and anhydrous and degazed toluene (9 ml) and heated to 120° C. with stirring for 24 hours. The cooled reaction mixture was treated with water and extracted with ethyl acetate. The combined organic layers were dried over MgSO4, filtered and evaporated under reduced pressure before purification by dry flash chromatography over SiO2 eluting with EtOAc/cyclohexane 20/80 to give 5-(6-bromopyridin-2-yl)-2-(4-methoxyphenyl)thiazole (410 mg, 59%). 1H NMR (300 MHz, DMSO-d6) δ 8.55 (s, 1H), 8.06 (d, J=7.2 Hz, 1H), 7.96 (d, J=8.3 Hz, 2H), 7.82 (t, J=7.8 Hz, 1H), 7.57 (d, J=7.3 Hz, 1H), 7.07 (d, J=8.5 Hz, 2H), 3.83 (s, 3H).
Reaction SMILES: [CH3:1][O:2][CH2:3][CH:4]1[O:8][C:7](=[O:9])[N:6]([C:10]2[CH:15]=[CH:14][C:13]([CH:16]3[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]3)=[CH:12][CH:11]=2)[CH2:5]1.[C:22](OC(=O)C)(=[O:24])[CH3:23].N1C=CC=CC=1>C(Cl)Cl>[C:22]([N:19]1[CH2:20][CH2:21][CH:16]([C:13]2[CH:12]=[CH:11][C:10]([N:6]3[CH2:5][CH:4]([CH2:3][O:2][CH3:1])[O:8][C:7]3=[O:9])=[CH:15][CH:14]=2)[CH2:17][CH2:18]1)(=[O:24])[CH3:23]
Reactant: CC(=O)OC(C)=O
Reactant: COCC1CN(c2ccc(C3CCNCC3)cc2)C(=O)O1
Solvent: c1ccncc1
Solvent: ClCCl
Product: COCC1CN(c2ccc(C3CCN(C(C)=O)CC3)cc2)C(=O)O1
Temperature: 25 °C
Reaction time: 18 h
Yield: 97.3 %

Procedure:
177.1 mg (0.61 mmol) of (RS)-4-[4-(5-methoxymethyl-2-oxo-oxazolidin-3-yl)-phenyl]-piperidine were dissolved in 20 ml of methylene chloride and treated with 68.5 mg (0.67 mmol) of acetic anhydride in the presence of 53.1 mg (0.67 mmol) of pyridine. After stirring at room temperature for 18 hours the mixture was washed with water and the organic phase was dried over sodium sulfate. After filtration and evaporation of the filtrate the product was dried in a high vacuum. 197.3 mg of (RS)-1-acetyl-4-[4-(5-methoxymethyl-2-oxo-oxazolidin-3-yl)-phenyl]-piperidine were obtained as a yellowish oil. 1H-NMR (CDCl3) ppm: 7.49 (d,2H), 7.20 (d,2H), 4.80 (m,2H), 4.05 (t, 1H), 3.92 (m,2H), 3.64 (d,2H), 3.43 (s,3H), 3.21 (m,1H), 2.68 (m,2H), 2.14 (s,3H), 1.85 (m,2H), 1.60 (m,2H).
Reaction SMILES: [Cl:1][C:2]1[N:10]=[C:9]2[C:5]([NH:6][CH:7]=[N:8]2)=[C:4](Cl)[N:3]=1.[N+:12]([C:15]1[CH:21]=[CH:20][C:18]([NH2:19])=[CH:17][CH:16]=1)([O-:14])=[O:13]>CN(C=O)C.C(O)CCC>[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([NH:6][CH:7]=[N:8]2)=[C:4]([NH:19][C:18]2[CH:20]=[CH:21][C:15]([N+:12]([O-:14])=[O:13])=[CH:16][CH:17]=2)[N:3]=1
Reactant: Nc1ccc([N+](=O)[O-])cc1
Reactant: Clc1nc(Cl)c2[nH]cnc2n1
Solvent: CN(C)C=O
Solvent: CCCCO
Product: O=[N+]([O-])c1ccc(Nc2nc(Cl)nc3nc[nH]c23)cc1

Procedure:
1.9 g (10 mmol) of 2,6-dichloro-purine are stirred in 40 ml of DMF/n-butanol (1:3) with 4.1 g (30 mmol) of 4-nitro-aniline at 130° C. for 24 h and the crystal mass which precipitates out on cooling is filtered off and dried in vacuo. 2-Chloro-6-(4-nitro-phenyl-amino)-purine is obtained; m.p.>270° C.; FAB-MS: (M+H)+=291; Rf=0.6 (CH2Cl2:methanol=9:1).
Reaction SMILES: [Si:1]([O:8][CH2:9][C:10]1([CH2:13][OH:14])[CH2:12][CH2:11]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].C(N(CC)CC)C.[CH3:22][S:23](Cl)(=[O:25])=[O:24]>C(Cl)Cl.O>[CH3:22][S:23]([O:14][CH2:13][C:10]1([CH2:9][O:8][Si:1]([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2])[CH2:11][CH2:12]1)(=[O:25])=[O:24]
Reactant: CC(C)(C)[Si](C)(C)OCC1(CO)CC1
Reactant: CS(=O)(=O)Cl
Solvent: O
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(C)(C)[Si](C)(C)OCC1(COS(C)(=O)=O)CC1
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
A solution of [1-({[tert-butyl(dimethyl)silyl]oxy}methyl)cyclopropyl]methanol (Example 34c, 5.37 g) dissolved in DCM (20 mL) was treated with triethylamine (6.92 mL) at 0° C. before adding methanesulfonyl chloride (2.321 mL) under nitrogen. The resulting mixture was stirred at 0° C. for 30 min. The reaction mixture was diluted with water (100 mL), and extracted with DCM (250 mL). The organics were dried (MgSO4), filtered and evaporated. The crude product was purified (SiO2 chromatography, elution 50% isohexane in diethyl ether). Pure fractions were evaporated to dryness to afford the subtitle compound (5.37 g) as an oil.
Reaction SMILES: [Cl:1][C:2]1[N:3]=[CH:4][C:5]2[C:10](I)=[CH:9][N:8]([C:12]([CH3:17])([CH3:16])[CH2:13][O:14][CH3:15])[C:6]=2[N:7]=1.[Br:18][C:19]1[CH:20]=[N:21][CH:22]=[C:23]([CH:30]=1)[C:24](N(OC)C)=[O:25]>>[Br:18][C:19]1[CH:30]=[C:23]([C:24]([C:10]2[C:5]3[CH:4]=[N:3][C:2]([Cl:1])=[N:7][C:6]=3[N:8]([C:12]([CH3:17])([CH3:16])[CH2:13][O:14][CH3:15])[CH:9]=2)=[O:25])[CH:22]=[N:21][CH:20]=1
Reactant: CON(C)C(=O)c1cncc(Br)c1
Reactant: COCC(C)(C)n1cc(I)c2cnc(Cl)nc21
Product: COCC(C)(C)n1cc(C(=O)c2cncc(Br)c2)c2cnc(Cl)nc21

Procedure:
The title compound was prepared according to the method described for Preparation 64 using 2-Chloro-5-iodo-7-(2-methoxy-1,1-dimethyl-ethyl)-7H-pyrrolo[2,3-d]pyrimidine (Preparation 259) and 5-Bromo-N-methoxy-N-methyl-nicotinamide to afford the title compound as yellow gum in 34% yield, 900 mg.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[N:10][C:11]3[N:12]([N:14]=[CH:15][C:16]=3[C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH:13]=2)=[CH:4][CH:3]=1.[CH2:23]([OH:26])[C:24]#[CH:25]>N1CCCC1.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>[C:17]1([C:16]2[CH:15]=[N:14][N:12]3[CH:13]=[C:8]([C:5]4[CH:6]=[CH:7][C:2]([C:25]#[C:24][CH2:23][OH:26])=[CH:3][CH:4]=4)[CH:9]=[N:10][C:11]=23)[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1
Reactant: C#CCO
Reactant: Brc1ccc(-c2cnc3c(-c4ccccc4)cnn3c2)cc1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCNC1
Product: OCC#Cc1ccc(-c2cnc3c(-c4ccccc4)cnn3c2)cc1

Procedure:
A deoxygenated mixture of 6-(4-bromophenyl)-3-phenylpyrazolo[1,5-a]pyrimidine (2-2, 3.00 g, 8.57 mmol, 1 equiv), propargyl alcohol (1.50 mL, 25.8 mmol, 3.01 equiv), and tetrakis(triphenylphosphine)palladium (0.500 g, 0.433 mmol, 0.050 equiv) in pyrrolidine (50 mL) was heated at reflux for 2.5 hours. The reaction mixture was concentrated, and the residue was suspended in methanol (50 mL) and filtered to give 3-[4-(3-phenylpyrazolo[1,5-a]pyrimidin-6-yl)phenyl]prop-2-yn-1-ol (2-3) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ9.56 (d, 1H, J=2.4 Hz), 9.07 (d, 1H, J=2.2 Hz), 8.82 (s, 1H), 8.18 (br d, 2H, J=7.8 Hz), 7.92 (d, 2H, J=8.2 Hz), 7.58 (d, 2H, J=8.2 Hz), 7.46 (t, 2H, J=7.8 Hz), 7.27 (t, 1H, J=7.8 Hz), 5.37 (t, 1H, J=6.0 Hz), 4.35 (d, 2H, J=6.0 Hz).
Reaction SMILES: [H-].[Na+].[CH2:3]([OH:8])[C:4]([F:7])([F:6])[F:5].[Cl:9][C:10]1[CH:15]=[C:14]([CH2:16]Cl)[CH:13]=[C:12]([F:18])[CH:11]=1.O>CN(C)C=O>[Cl:9][C:10]1[CH:15]=[C:14]([CH2:16][O:8][CH2:3][C:4]([F:7])([F:6])[F:5])[CH:13]=[C:12]([F:18])[CH:11]=1
Reactant: Fc1cc(Cl)cc(CCl)c1
Reactant: OCC(F)(F)F
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: Fc1cc(Cl)cc(COCC(F)(F)F)c1
Reaction time: 0.25 h

Procedure:
Under argon stream, to a suspension of sodium hydride (601 mg, 60 wt. % oil dispersion) in dimethylformamide (13 ml) was added dropwise trifluoroethanol (1.08 ml) at 0° C., and the mixture was stirred for 15 minutes. To this reaction solution was added dropwise a solution of 1-chloro-3-fluoro-5-chloromethylbenzene (2.23 g) in dimethylformamide (9 ml), and then the mixture was stirred at room temperature for 1 hour. To this reaction mixture was added water, and the mixture was extracted with a mixed solvent of n-hexane/ethyl acetate=1/1. This organic layer was washed with a saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (eluent: n-hexane/ethyl acetate=1/0 to 9/1) to give the titled compound (2.85 g).
Reaction SMILES: [BH4-].[Na+].O1CCCC1.[Cl:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([N+:15]([O-:17])=[O:16])[C:10]=1[CH2:18][C:19](O)=[O:20].C(=O)([O-])O.[Na+]>C(Cl)Cl.O>[Cl:8][C:9]1[C:10]([CH2:18][CH2:19][OH:20])=[C:11]([N+:15]([O-:17])=[O:16])[CH:12]=[CH:13][CH:14]=1
Reactant: O=C(O)Cc1c(Cl)cccc1[N+](=O)[O-]
Agent: O=C([O-])O
Agent: [BH4-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: ClCCl
Solvent: O
Product: O=[N+]([O-])c1cccc(Cl)c1CCO
Reaction time: 0.5 h
Yield: 85.5 %

Procedure:
2.26 g (59.8 mmol) of sodium borohydride was added to 7 ml of tetrahydrofuran, and while cooling on ice, 15 ml of tetrahydrofuran solution containing 6.78 g (31.5 mmol) of the compound (137) obtained above was dropped to the solution through 20 minutes. Then, 15 ml of tetrahydrofuran solution containing 10 ml of borontrifluoride-ether complex was dropped to the solution through 10 minutes, and after stirring for 30 minutes as was, the solution was stirred for 1 hour at room temperature. To 130 ml of water containing 9.6 g of sodium hydrogen carbonate and 170 ml of methylene chloride, the reaction solution was added slowly, and the obtained solution was stirred overnight at room temperature. The organic layer was separated, and after drying over magnesium sulfate, the solvent was removed by distillation. To the residue, n-hexane was added to crystallize, and the crystals were filtered off and washed with n-hexane to obtain 5.43 g of the subject compound (138) in a 86% yield.
Reaction SMILES: [F:1][C:2]1[CH:38]=[C:37]([F:39])[CH:36]=[C:35]([F:40])[C:3]=1[CH2:4][N:5]1[C:13]([C:14]2[CH:15]=[C:16]([C:20]#[C:21][C:22]3[CH:23]=[C:24]([CH:28]=[CH:29][CH:30]=3)[C:25]([OH:27])=O)[CH:17]=[CH:18][CH:19]=2)=[C:12]2[C:7]([C:8]([C:31]([F:34])([F:33])[F:32])=[CH:9][CH:10]=[CH:11]2)=[N:6]1.Cl.CN.C(C1NC=CN=1)([C:46]1[NH:47]C=CN=1)=O>CN(C=O)C>[CH3:46][NH:47][C:25](=[O:27])[C:24]1[CH:28]=[CH:29][CH:30]=[C:22]([C:21]#[C:20][C:16]2[CH:17]=[CH:18][CH:19]=[C:14]([C:13]3[N:5]([CH2:4][C:3]4[C:2]([F:1])=[CH:38][C:37]([F:39])=[CH:36][C:35]=4[F:40])[N:6]=[C:7]4[C:12]=3[CH:11]=[CH:10][CH:9]=[C:8]4[C:31]([F:32])([F:33])[F:34])[CH:15]=2)[CH:23]=1
Reactant: O=C(O)c1cccc(C#Cc2cccc(-c3c4cccc(C(F)(F)F)c4nn3Cc3c(F)cc(F)cc3F)c2)c1
Reactant: O=C(c1ncc[nH]1)c1ncc[nH]1
Agent: CN
Agent: Cl
Solvent: CN(C)C=O
Product: CNC(=O)c1cccc(C#Cc2cccc(-c3c4cccc(C(F)(F)F)c4nn3Cc3c(F)cc(F)cc3F)c2)c1
Yield: 39.7 %

Procedure:
A solution of 3-({3-[2-(2,4,6-trifluorobenzyl)-7-(trifluoromethyl)-2H-indazol-3-yl]phenyl}ethynyl)benzoic acid (0.042 g, 0.076 mmol), methyl amine-HCl (0.006 g, 0.076 mmol) and carbonyl diimidazole (0.013 g, 0.076 mmol) in 2 mL DMF was stirred at ambient temperature overnight. The reaction mixture was partitioned with ethyl acetate and H2O. The organic phase was concentrated in vacuo and purified by flash chromatography (silica 60, CH2Cl2—CH3OH, 25:1) to give 0.017 g of the product.