Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([O:5][C:6](=[O:16])[NH:7][C:8]1[CH:13]=[C:12]([F:14])[CH:11]=[CH:10][C:9]=1Br)([CH3:4])([CH3:3])[CH3:2].B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.[F-].[Cs+].[CH2:56]([O:63][C:64]1[CH:65]=[C:66]2[C:71](=[CH:72][CH:73]=1)[C:70]([C:74](=[O:90])[C:75]1[CH:80]=[CH:79][C:78]([O:81][CH2:82][CH2:83][N:84]3[CH2:89][CH2:88][CH2:87][CH2:86][CH2:85]3)=[CH:77][CH:76]=1)=[C:69](OS(C(F)(F)F)(=O)=O)[CH:68]=[CH:67]2)[C:57]1[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(#N)C>[C:1]([O:5][C:6](=[O:16])[NH:7][C:8]1[CH:13]=[C:12]([F:14])[CH:11]=[CH:10][C:9]=1[C:69]1[CH:68]=[CH:67][C:66]2[C:71](=[CH:72][CH:73]=[C:64]([O:63][CH2:56][C:57]3[CH:58]=[CH:59][CH:60]=[CH:61][CH:62]=3)[CH:65]=2)[C:70]=1[C:74](=[O:90])[C:75]1[CH:80]=[CH:79][C:78]([O:81][CH2:82][CH2:83][N:84]2[CH2:85][CH2:86][CH2:87][CH2:88][CH2:89]2)=[CH:77][CH:76]=1)([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)OC(=O)Nc1cc(F)ccc1Br
Reactant: O=C(c1ccc(OCCN2CCCCC2)cc1)c1c(OS(=O)(=O)C(F)(F)F)ccc2cc(OCc3ccccc3)ccc12
Agent: [Pd+2]
Agent: C1CCC(P(C2CCCCC2)C2CCCCC2)CC1
Agent: CC(=O)[O-]
Solvent: CC#N
Product: CC(C)(C)OC(=O)Nc1cc(F)ccc1-c1ccc2cc(OCc3ccccc3)ccc2c1C(=O)c1ccc(OCCN2CCCCC2)cc1
Temperature: 25 °C
Reaction time: 0.08 h
Yield: 36.4 %

Procedure:
Add (2-bromo-5-fluoro-phenyl)-carbamic acid tert-butyl ester (1.06 g, 3.67 mmol), bis(pinacolato)diboron (1.03 g, 4.04 mmol), palladium(II) acetate (0.062 g, 0.28 mmol), tricyclohexylphosphine (0.103 g, 0.37 mmol) and acetonitrile (40 mL) to a round bottom flask. Stir at ambient temperature for approximately 5 minutes to dissolve most of the reagents. Add cesium fluoride (2.10 g, 13.82 mmol), place the flask in a 90° C. oil bath, and stir for 30-45 minutes. Remove the oil bath and allow the reaction mixture to cool to ambient temperature. To this mixture, add trifluoromethanesulfonic acid 6-benzyloxy-1-[4-(2-piperidin-1-yl-ethoxy)-benzoyl]-naphthalen-2-yl ester (0.75 g, 1.22 mmol), palladium(II) acetate (0.062 g, 0.28 mmol), tricyclohexylphosphine (0.103 g, 0.37 mmol) and place the reaction in a 90° C. oil bath. Stir the reaction for 4 hours at 90° C. Cool the reaction to ambient temperature, filter it through a pad of Celite and rinse the pad with ample, hot ethyl acetate. Wash the filtrate with 50% aqueous sodium carbonate, saturated aqueous ammonium chloride, H2O and brine; then dry (sodium sulfate) and evaporate it in vacuo. Load the resulting material onto an SCX column. Wash with dichloromethane, 50% dichloro-methane/methanol, elute with ammonia solution (2N NH3 in methanol) and remove solvent under vacuum. Purify the resulting residue by flash chromatography (silica gel; 1%-5% methanol gradient in dichloromethane: followed by a second chromatography 2% of 2N NH3 in methanol/25% THF/hexanes: followed by purification on a Chromatotron; 2% MeOH/dichloromethane) to provide 0.300 g (36%) of the title compound: mass spectrum (ion spray) m/z=675 (M+H).
Reaction SMILES: [CH:1]1([C:7]2(O)[C:11]3[C:12]([CH3:26])=[C:13]([NH:18][C:19](=[O:25])[CH2:20][C:21]([CH3:24])([CH3:23])[CH3:22])[C:14]([CH3:17])=[C:15]([CH3:16])[C:10]=3[O:9][C:8]2([CH3:28])[CH3:27])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1>C(OCC)(=O)C.CCCCCC>[CH:1]1([CH:7]2[C:11]3[C:12]([CH3:26])=[C:13]([NH:18][C:19](=[O:25])[CH2:20][C:21]([CH3:22])([CH3:23])[CH3:24])[C:14]([CH3:17])=[C:15]([CH3:16])[C:10]=3[O:9][C:8]2([CH3:28])[CH3:27])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1
Reactant: Cc1c(C)c2c(c(C)c1NC(=O)CC(C)(C)C)C(O)(C1CCCCC1)C(C)(C)O2
Solvent: CCOC(C)=O
Solvent: CCCCCC
Product: Cc1c(C)c2c(c(C)c1NC(=O)CC(C)(C)C)C(C1CCCCC1)C(C)(C)O2
Yield: 48 %

Procedure:
Using N-(3-cyclohexyl-3-hydroxy-2,2,4,6,7-pentamethyl-2,3-dihydro-1-benzofuran-5-yl)-3,3-dimethylbutanamide obtained in Example 256, the title compound was synthesized in the same manner as in Example 271. Yield: 48%. Melting point: 198-199° C. (ethyl acetate-hexane).
Reaction SMILES: [C:1]1([C:7]2[CH:12]=[CH:11][N:10]=[C:9]([C:13]3[CH:25]=[CH:24][C:23]4[C:22]5[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=5)[NH:16][C:15]=4[CH:14]=3)[CH:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Br[C:27]1[CH:39]=[CH:38][C:37]2[C:36]3[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=3)[N:30]([C:40]3[CH:45]=[C:44]([C:46]([CH3:49])([CH3:48])[CH3:47])[CH:43]=[CH:42][N:41]=3)[C:29]=2[CH:28]=1.CC(P(C(C)(C)C)C1C(C2C=CC=CC=2)=CC=CC=1)(C)C.CC([O-])(C)C.[Na+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:46]([C:44]1[CH:43]=[CH:42][N:41]=[C:40]([N:30]2[C:29]3[CH:28]=[C:27]([N:16]4[C:15]5[CH:14]=[C:13]([C:9]6[CH:8]=[C:7]([C:1]7[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=7)[CH:12]=[CH:11][N:10]=6)[CH:25]=[CH:24][C:23]=5[C:22]5[C:17]4=[CH:18][CH:19]=[CH:20][CH:21]=5)[CH:39]=[CH:38][C:37]=3[C:36]3[C:31]2=[CH:32][CH:33]=[CH:34][CH:35]=3)[CH:45]=1)([CH3:49])([CH3:47])[CH3:48]
Reactant: c1ccc(-c2ccnc(-c3ccc4c(c3)[nH]c3ccccc34)c2)cc1
Reactant: CC(C)(C)c1ccnc(-n2c3ccccc3c3ccc(Br)cc32)c1
Agent: [Pd]
Agent: CC(C)(C)P(c1ccccc1-c1ccccc1)C(C)(C)C
Agent: CC(C)(C)[O-]
Product: CC(C)(C)c1ccnc(-n2c3ccccc3c3ccc(-n4c5ccccc5c5ccc(-c6cc(-c7ccccc7)ccn6)cc54)cc32)c1
Temperature: 100 °C
Reaction time: 43 h

Procedure:
To a dry pressure Schlenk tube equipped with a magnetic stir bar was added 2-(4-phenylpyridin-2-yl)-9H-carbazole (676 mg, 2.11 mmol, 1.0 eq), 2-bromo-9-(4-tert-butylpyridin-2-yl)-9H-carbazole (958 mg, 2.53 mmol, 1.2 eq), Pd2(dba)3 (77 mg, 0.084 mmol, 0.04 eq), JohnPhos (50 mg, 0.169 mmol, 0.08 eq) and tBuONa (324 mg, 3.38 mmol, 1.6 eq). Then the tube was evacuated and back-filled with nitrogen, and the evacuation and back-fill procedure was repeated twice. Then dry solvent toluene (10 mL), dioxane (10 mL) were added under the protection of nitrogen. The tube was sealed and the mixture was stirred in an oil bath at a temperature of 95-105° C. for 43 hours. Then the mixture was cooled to ambient temperature. The solvent was removed under reduced pressure and the residue was purified through column chromatography on silica gel using hexane and ethyl acetate (10:1-8:1-5:1) as an eluent to obtain the desired product, 9-(4-tert-butylpyridin-2-yl)-2′-(4-phenylpyridin-2-yl)-9H-2,9′-bicarbazole Ligand N3NPh-ptb, as a brown solid (1175 mg in 90% yield). 1H NMR (DMSO-d6, 400 MHz): δ 1.15 (s, 9H), 7.25 (t, J=8.0 Hz, 1H), 7.31 (dd, J=5.2, 1.6 Hz, 1H), 7.34-7.57 (m, 9H), 7.74 (s, 1H), 7.78-7.82 (m, 3H), 7.91 (d, J=1.6 Hz, 1H), 8.11 (d, J=8.4 Hz, 1H), 8.21 (s, 1H), 8.24 (d, J=8.0 Hz, 1H), 8.29 (s, 1H), 8.31 (d, J=8.4 Hz, 2H), 8.45 (d, J=6.0 Hz, 1H), 8.51 (d, J=8.0 Hz, 1H), 8.57 (d, J=4.2 Hz, 1H). 13C NMR (DMSO-d6, 100 MHz): δ 29.96, 34.72, 108.01, 109.82, 109.85, 111.36, 115.97, 117.92, 119.14, 119.31, 119.80, 119.92, 120.23, 120.72, 120.84, 121.29, 122.00, 122.39, 122.94, 123.02, 123.45, 126.63, 126.84, 127.05, 129.06, 129.16, 134.83, 136.92, 137.49, 139.73, 139.78, 141.13, 141.47, 148.33, 149.39, 149.97, 150.55, 157.15, 163.08.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][C:13]([CH3:18])=[C:12]2[C:19]([O:21][CH2:22][CH3:23])=[O:20])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.I[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].CNCCNC>C1(C)C=CC=CC=1.[Cu]I>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[N:14]([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[C:13]([CH3:18])=[C:12]2[C:19]([O:21][CH2:22][CH3:23])=[O:20])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CCOC(=O)c1c(C)[nH]c2ccc(OCc3ccccc3)cc12
Reactant: Ic1ccccc1
Agent: [Cu]I
Agent: CNCCNC
Agent: O=P([O-])([O-])[O-]
Solvent: Cc1ccccc1
Product: CCOC(=O)c1c(C)n(-c2ccccc2)c2ccc(OCc3ccccc3)cc12
Temperature: 140 °C
Yield: 74.9 %

Procedure:
To a mixture of 5-benzyloxy-2-methyl-1H-indole-3-carboxylic acid, ethyl ester (Compound 53, 0.14 g, 0.45 mmol) in toluene (6 ml) having been degassed under argon for 15 min. was added 2-iodo-benzene (0.10 ml, 0.48 g, 0.88 mmol), potassium phosphate (0.20 g, 0.94 mmol), copper (I) iodide (24 mg, 0.13 mmol), and then N,N′-dimethylethylenediamine (12 mg, 0.14 mmol) with continued degassing. The tube was then sealed and mixture was heated at 140° C. for 24 h. The reaction was then cooled and filtered. The filtrate was concentrated under reduced pressure and the crude product residue was purified by flash column chromatography on silica gel (30% EtOAc-hexanes) to yield 5-benzyloxy-2-methyl-1-phenyl-1H-indole-3-carboxylic acid, ethyl ester (Compound 54) as an orange oil (0.13 g, 76%).
Reaction SMILES: [Br:1][C:2]1[CH:32]=[CH:31][CH:30]=[CH:29][C:3]=1[NH:4][CH2:5][C:6]1[C:7]([NH:14][C:15]2[CH:20]=[CH:19][C:18]([CH2:21][O:22][CH:23]3[CH2:28][CH2:27][CH2:26][CH2:25][O:24]3)=[CH:17][CH:16]=2)=[N:8][C:9]([S:12][CH3:13])=[N:10][CH:11]=1.C(N(CC)CC)C.[C:40](Cl)(Cl)=[O:41]>O1CCCC1.C1(C)C=CC=CC=1>[Br:1][C:2]1[CH:32]=[CH:31][CH:30]=[CH:29][C:3]=1[N:4]1[CH2:5][C:6]2[C:7](=[N:8][C:9]([S:12][CH3:13])=[N:10][CH:11]=2)[N:14]([C:15]2[CH:16]=[CH:17][C:18]([CH2:21][O:22][CH:23]3[CH2:28][CH2:27][CH2:26][CH2:25][O:24]3)=[CH:19][CH:20]=2)[C:40]1=[O:41]
Reactant: CSc1ncc(CNc2ccccc2Br)c(Nc2ccc(COC3CCCCO3)cc2)n1
Reactant: O=C(Cl)Cl
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Solvent: Cc1ccccc1
Product: CSc1ncc2c(n1)N(c1ccc(COC3CCCCO3)cc1)C(=O)N(c1ccccc1Br)C2
Temperature: 0 °C
Reaction time: 1 h
Yield: 97 %

Procedure:
A solution containing 0.93 g (1.8 mmol) of 5-(2-bromoanilino)methyl-4-[4-(tetrahydropyran-2-yloxymethyl)phenyl]amino-2-methylthiopyrimidine and 0.5 ml (3.61 mmol) of triethylamine in 5 ml of anhydrous tetrahydrofuran was added dropwise to 1.9 ml (3.61 mmol) of a 20% solution of phosgene in toluene dissolved in 5 ml of tetrahydrofuran at 0° C. under an atmosphere of nitrogen. The reaction was stirred at 0° C. for a further 60 minutes then evaporated. The residue was partitioned between ethyl acetate (10 ml) and 2M hydrochloric acid (10 ml), the ethyl acetate layer was separated then washed with saturated aqueous sodium bicarbonate (10 ml), dried over magnesium sulfate, filtered and evaporated to give 0.945 g (97%) of 3-(2-bromophenyl)-3,4-dihydro-1-[4-(tetrahydropyran-2-yloxymethyl)phenyl]-7-methylthio-pyrimido[4,5-d]pyrimidin-2(1H)-one as a yellow gum. [Mass spectrum (ESI) MH+ =541].
Reaction SMILES: [CH3:1][O:2][CH2:3][O:4][C@H:5]1[CH2:9][CH2:8][N:7]([CH2:10][C@H:11]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)O)[CH2:6]1.COCO[C@H]1CCN([C@H](C2C=CC=CC=2)CO)C1.[CH3:37][O:38][C:39]1[CH:48]=[C:47]([NH:49][CH3:50])[CH:46]=[CH:45][C:40]=1[C:41]([O:43][CH3:44])=[O:42]>>[CH3:37][O:38][C:39]1[CH:48]=[C:47]([N:49]([C@@H:11]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH2:10][N:7]2[CH2:8][CH2:9][C@H:5]([O:4][CH2:3][O:2][CH3:1])[CH2:6]2)[CH3:50])[CH:46]=[CH:45][C:40]=1[C:41]([O:43][CH3:44])=[O:42]
Reactant: CNc1ccc(C(=O)OC)c(OC)c1
Reactant: COCO[C@H]1CCN(C[C@@H](O)c2ccccc2)C1
Agent: COCO[C@H]1CCN([C@@H](CO)c2ccccc2)C1
Product: COCO[C@H]1CCN(C[C@H](c2ccccc2)N(C)c2ccc(C(=O)OC)c(OC)c2)C1
Yield: 41 %

Procedure:
This was prepared from 2-(3-(S)-methoxymethoxypyrrolidin-1-yl)-1-(S)-phenylethanol and 2-(3-(S)-methoxymethoxypyrrolidin-1-yl)-2-(R)-phenylethanol and methyl 2-methoxy-4-methylaminobenzoate in 41% yield according to a procedure similar to that described in Example 1 (i).
Reaction SMILES: [CH3:1][O:2][C:3]1[N:8]=[CH:7][C:6]([C:9]2[N:17]3[C:12]([CH:13]=[N:14][C:15](O)=[N:16]3)=[CH:11][CH:10]=2)=[CH:5][CH:4]=1.[NH2:19][C:20]1[CH:21]=[C:22]2[C:27](=[CH:28][CH:29]=1)[CH2:26][N:25]([CH2:30][C:31]([NH2:33])=[O:32])[CH2:24][CH2:23]2>>[CH3:1][O:2][C:3]1[N:8]=[CH:7][C:6]([C:9]2[N:17]3[C:12]([CH:13]=[N:14][C:15]([NH:19][C:20]4[CH:21]=[C:22]5[C:27](=[CH:28][CH:29]=4)[CH2:26][N:25]([CH2:30][C:31]([NH2:33])=[O:32])[CH2:24][CH2:23]5)=[N:16]3)=[CH:11][CH:10]=2)=[CH:5][CH:4]=1
Reactant: NC(=O)CN1CCc2cc(N)ccc2C1
Reactant: COc1ccc(-c2ccc3cnc(O)nn23)cn1
Product: COc1ccc(-c2ccc3cnc(Nc4ccc5c(c4)CCN(CC(N)=O)C5)nn23)cn1

Procedure:
7-(6-Methoxy-pyridin-3-yl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol (0.0609 g, 0.251 mmol) and 2-(6-Amino-3,4-dihydro-1H-isoquinolin-2-yl)-acetamide (0.064 g, 0.31) were reacted in an analogous manner to Example 908D at 50° C. for 16 h. The reaction mixture was concentrated and purified by Gilson RP-HPLC. HPLC rt=2.083 min, purity=91%. 1H NMR (400 MHz, (D3C)2SO, δ, ppm): 10.23 (bs, 1H), 9.63 (s, 1H), 9.10 (s, 1H), 9.01 (s, 1H), 8.44 (dd, J=8.9 Hz, 2.2 Hz, 1H), 7.96 (s, 1H), 7.91 (s, 1H), 7.75 (s, 1H), 7.40 (d, J=8.9 Hz, 1H), 7.21 (d, J=4.4 Hz, 1H), 7.13 (d, J=8.9 Hz, 1H), 7.04 (d, J=8.6 Hz, 1H), 6.98 (d, J=4.5 Hz, 1H), 4.50 (m, 1H), 4.33 (m, 1H), 4.05 (m, 2H), 3.95 (s, 3H), 3.70 (m, 1H), 3.43 (m, 1H), 3.23 (m, 1H), 3.08 (m, 1H).
Reaction SMILES: [CH2:1]([C:8]1([OH:14])[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br[CH2:16][C:17]#[N:18]>>[CH2:1]([C:8]1([OH:14])[CH2:13][CH2:12][N:11]([CH2:16][C:17]#[N:18])[CH2:10][CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: OC1(Cc2ccccc2)CCNCC1
Reactant: N#CCBr
Product: N#CCN1CCC(O)(Cc2ccccc2)CC1

Procedure:
The title compound is synthesized by coupling of 4-Benzyl-4-hydroxy-piperidine (commercially available from ABCR GmbH) and bromoacetonitrile analogously to the preparation of Intermediate 149.2 as a colorless oil; ES-MS: M+=231.2: AtRet=1.81.
Reaction SMILES: [NH2:1][CH2:2][C:3]([NH:5][C@H:6]([C:16]([NH:18][C@H:19]([C:39]([O:41][CH3:42])=[O:40])[CH2:20][CH2:21][CH2:22][NH:23][C:24](=[NH:38])[NH:25][S:26]([C:29]1[C:36]([CH3:37])=[CH:35][C:33]([CH3:34])=[CH:32][C:30]=1[CH3:31])(=[O:28])=[O:27])=[O:17])[CH2:7][O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)=[O:4].[NH:43]([C:52]([O:54][C:55]([CH3:58])([CH3:57])[CH3:56])=[O:53])[C@H:44]([C:49](O)=[O:50])[C@H:45]([CH2:47][CH3:48])[CH3:46].C1C=CC(P(N=[N+]=[N-])(C2C=CC=CC=2)=O)=CC=1.C(N(CC)CC)C>CN(C=O)C.O1CCOCC1>[NH:43]([C:52]([O:54][C:55]([CH3:57])([CH3:56])[CH3:58])=[O:53])[C@H:44]([C:49]([NH:1][CH2:2][C:3]([NH:5][C@H:6]([C:16]([NH:18][C@H:19]([C:39]([O:41][CH3:42])=[O:40])[CH2:20][CH2:21][CH2:22][NH:23][C:24](=[NH:38])[NH:25][S:26]([C:29]1[C:30]([CH3:31])=[CH:32][C:33]([CH3:34])=[CH:35][C:36]=1[CH3:37])(=[O:27])=[O:28])=[O:17])[CH2:7][O:8][CH2:9][C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1)=[O:4])=[O:50])[C@H:45]([CH2:47][CH3:48])[CH3:46]
Reactant: CC[C@H](C)[C@H](NC(=O)OC(C)(C)C)C(=O)O
Reactant: COC(=O)[C@H](CCCNC(=N)NS(=O)(=O)c1c(C)cc(C)cc1C)NC(=O)[C@H](COCc1ccccc1)NC(=O)CN
Agent: [N-]=[N+]=NP(=O)(c1ccccc1)c1ccccc1
Solvent: CN(C)C=O
Solvent: C1COCCO1
Solvent: CCN(CC)CC
Product: CC[C@H](C)[C@H](NC(=O)OC(C)(C)C)C(=O)NCC(=O)N[C@@H](COCc1ccccc1)C(=O)N[C@@H](CCCNC(=N)NS(=O)(=O)c1c(C)cc(C)cc1C)C(=O)OC
Temperature: 0 °C
Reaction time: 0.17 h

Procedure:
The Boc group of product (XIII) was removed by the same method as described in regard to compound (XI) to give 0.40 g (0.63 mmol) of HCl.H-Gly-Ser(Bzl)-Arg(Mts)-OMe. It was then dissolved in a mixed solvent of 5.4 ml of rectified DMF and 5.4 ml of dioxane together with the equimolar amount (0.14 g) of Boc-Ile-OH. The resulting solution was stirred at 0° C. for 10 minutes and then 0.21 ml of DPPA and 0.20 ml of triethylamine were added. The mixture was stirred at room temperature for 24 hours. The solution thus obtained was freed from any acidic and alkaline materials in the same manner as described in regard to compounds (XII) and (XIII). After drying, 0.28 g of Boc-Ile-Gly-Ser(Bzl)-Arg(Mts)-OMe was obtained.
Reaction SMILES: [N:1]([C@H:4]([CH3:31])[CH2:5][CH2:6][CH2:7][CH2:8][N:9]1[C:14](=[O:15])[C:13]2[C:16](=[O:28])[CH:17]=[C:18]([CH3:27])[N:19]([CH2:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[C:12]=2[N:11]([CH3:29])[C:10]1=[O:30])=[N+]=[N-].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O>O1CCCC1>[NH2:1][C@H:4]([CH3:31])[CH2:5][CH2:6][CH2:7][CH2:8][N:9]1[C:14](=[O:15])[C:13]2[C:16](=[O:28])[CH:17]=[C:18]([CH3:27])[N:19]([CH2:20][C:21]3[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=3)[C:12]=2[N:11]([CH3:29])[C:10]1=[O:30]
Reactant: Cc1cc(=O)c2c(=O)n(CCCC[C@@H](C)N=[N+]=[N-])c(=O)n(C)c2n1Cc1ccccc1
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Solvent: O
Product: Cc1cc(=O)c2c(=O)n(CCCC[C@@H](C)N)c(=O)n(C)c2n1Cc1ccccc1
Temperature: 25 °C
Reaction time: 18 h
Yield: 43.4 %

Procedure:
A mixture of (R)-3-(5-azidohexyl)-8-benzyl-1,7-dimethylpyrido[2,3-d]pyrimidine-2,4,5(1H,3H,8H)-trione (380 mg, 0.90 mmol), triphenylphosphine (260 mg, 0.99 mmol), water (0.1 ml) and tetrahydrofuran (15 ml) was stirred at room temperature for 18 hours followed by heating at 500 C for 4 hours. Another portion of triphenylphosphine (100 mg) was added and the mixture was heated at 65° C. for 18 hours. After concentration under reduced pressure, the residue was treated with 1.0 M aqueous hydrochloric acid (10 ml) and ethyl acetate (10 ml), followed by extraction of the organic layer with 1.0 M aqueous hydrochloric acid (2×10 ml). The combined aqueous layers were made slightly basic (pH˜8) by addition of aqueous potassium hydroxide solution and extracted with ethyl acetate (2×20 ml). The combined organic extracts were dried over sodium sulfate and concentrated under reduced pressure to afford (R)-3-(5-aminohexyl)-8-benzyl-1,7-dimethylpyrido[2,3-d]pyrimidine-2,4,5(1H,3H,8H)-trione (155 mg, 43% yield) as a beige powder. 1H NMR (300 MHz, CDCl3) δ 1.05 (d, 3H), 1.39 (broad s, 4H), 1.66 (m, 2H), 1.90 (broad s, 1H), 2.45 (s, 3H), 2.81 (broad s, 1H), 3.61 (s, 3H), 4.00 (t, 2H), 5.25 (s, 2H), 6.51 (s, 1H), 7.25-7.55 (m, 5H).
Reaction SMILES: Br[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([CH:8]=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][CH:12]=3)[N:10]=2)[CH:7]=1.[OH:18][CH2:19][C:20]1[CH:21]=[C:22](B(O)O)[CH:23]=[CH:24][CH:25]=1.C1(C)C=CC=CC=1.C(=O)([O-])[O-].[Na+].[Na+]>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.ClCCl.C(#N)C>[Cl:17][C:14]1[CH:15]=[CH:16][C:11]([C:9]2[N:10]=[C:5]3[CH:4]=[CH:3][C:2]([C:24]4[CH:25]=[C:20]([CH2:19][OH:18])[CH:21]=[CH:22][CH:23]=4)=[CH:7][N:6]3[CH:8]=2)=[CH:12][CH:13]=1
Reactant: OCc1cccc(B(O)O)c1
Reactant: Clc1ccc(-c2cn3cc(Br)ccc3n2)cc1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CC#N
Solvent: ClCCl
Solvent: Cc1ccccc1
Product: OCc1cccc(-c2ccc3nc(-c4ccc(Cl)cc4)cn3c2)c1
Yield: 76.6 %

Procedure:
Under a stream of nitrogen, 210 mg of 6-bromo-2-(4-chlorophenyl)imidazo[1,2-a]pyridine, 155 mg of 3-(hydroxymethyl)phenylboronic acid and 24 mg of tetrakis(triphenylphosphine)palladium are placed in a microwave tube containing 3 ml of toluene degassed beforehand under a stream of nitrogen, 3 ml of acetonitrile and 3 ml of a 2M solution of sodium carbonate. The tube is placed in a microwave apparatus and irradiated at 150° C. for 15 min. The organic phase is separated and dried and the filtrate is concentrated under reduced pressure. The residue obtained is taken up with dichloromethane. The precipitate is recovered by filtration, washed with dichloromethane and dried in a desiccator under reduced pressure. 175 mg of compound are obtained. Mp=181-182° C. 1H NMR (DMSO-d6, δ in ppm): 4.57 (d, J=5.5 Hz, 2H); 5.23 (t, J=5.6 Hz, 1H); from 7.28 to 7.71 (m, 8H); 7.97 (m, J=8.5 Hz, 2H); 8.41 (s, 1H); 8.84 (m, 1H). M+H=335.
Reaction SMILES: O.O.S([C:7]1C=CC(C)=CC=1)(O)(=O)=O.[NH2:14][C:15]1[C:23]([I:24])=[CH:22][CH:21]=[CH:20][C:16]=1[C:17]([NH2:19])=[O:18].C([O-])([O-])OC.CN1C(=O)CCC1>O>[I:24][C:23]1[CH:22]=[CH:21][CH:20]=[C:16]2[C:15]=1[NH:14][CH:7]=[N:19][C:17]2=[O:18]
Reactant: NC(=O)c1cccc(I)c1N
Reactant: Cc1ccc(S(=O)(=O)O)cc1
Agent: COC([O-])[O-]
Solvent: O
Solvent: CN1CCCC1=O
Product: O=c1nc[nH]c2c(I)cccc12
Yield: 968.9 %

Procedure:
Tosylic acid dihydrate (0.038 g) was added to a suspension of 2-amino-3-iodobenzamide (0.513 g) supplemented with methyl orthoformate (5 ml) and NMP (1 ml), and the mixture was heated to reflux for 3 hours. After cooling, water was added to the reaction solution, and the deposit was filtrated and dried under reduced pressure to obtain 8-iodoquinazolin-4(1H)-one (0.481 g). Phosphorus oxychloride (10 ml) was added to the obtained 8-iodoquinazolin-4(1H)-one (1.17 g), and the mixture was heated to reflux for 8 hours. The solvent was distilled off under reduced pressure, and chloroform was added to the residue. The reaction solution was neutralized with an aqueous sodium hydroxide solution with cooling in an ice bath and partitioned into organic and aqueous layers. The organic layer was washed with brine. The organic layer thus washed was dried over anhydrous sodium sulfate. Then, the solvent was distilled off, and the residue was purified by neutral silica gel column chromatography (chloroform/ethyl acetate) to obtain 4-chloro-8-iodoquinazoline (0.946 g). 4-(4-Chloroquinazolin-8-yl)-2-(4-hydroxycyclohexylamino)benzonitrile was obtained according to Example 2(1) using the obtained 4-chloro-8-iodoquinazoline instead of compound (1b) and PdCl2dppf instead of Pd(PPh3)4. A compound of Comparative Example 2 was obtained as a pale yellow solid (yield based on 5 steps: 10%) according to Example 79 using the obtained 4-(4-chloroquinazolin-8-yl)-2-(4-hydroxycyclohexylamino)benzonitrile instead of compound (4b) and 3-quinolineboronic acid instead of 3-(tert-butylamino)-4-cyanophenylboronic acid pinacol ester.
Reaction SMILES: CC([O-])(C)C.[K+].[C:7]([C:10]1C=CC=C[CH:11]=1)(=[O:9])[CH3:8].C1C=CC(CCO)=CC=1.C(C1C=CC=CC=1)(=O)C1C=CC=CC=1.C(O)(C1C=CC=CC=1)C1C=CC=CC=1.[CH3:53][C:54](=O)[C:55]([CH3:58])([CH3:57])[CH3:56]>>[C:55]([CH:54]1[CH2:11][CH2:10][C:7](=[O:9])[CH2:8][CH2:53]1)([CH3:58])([CH3:57])[CH3:56]
Reactant: CC(=O)C(C)(C)C
Reactant: CC(=O)c1ccccc1
Agent: CC(C)(C)[O-]
Agent: O=C(c1ccccc1)c1ccccc1
Agent: OC(c1ccccc1)c1ccccc1
Solvent: OCCc1ccccc1
Product: CC(C)(C)C1CCC(=O)CC1

Procedure:
Table 3 summarizes the hydrogenation of a variety of ketones and aldehydes using 1/KOtBu as hydrogenation catalyst at room temperature. Acetophenone was converted to phenylethanol even at high substrate to catalyst ratios (entries 1-3). Benzophenone was converted to benzhydrol under similarly mild reaction conditions. Unactivated dialkyl ketones were readily converted to their respective alcohols, including sterically congested and electronically deactivated pinacolone (entry 11). Reduction of 4-tert-butylcyclohexanone resulted in a 1:2 non-thermodynamic mixture of the cis and trans alcohols, respectively. The hydrogenation of conjugated ketones was also investigated. Benzalacetone was converted to the allyl alcohol as the only detectable product, whereas hydrogenation of cyclohex-2-enone resulted in a 1:1 mixture of the allyl and saturated alcohols. Only the carbonyl group of b-ionone was reduced to give the respective alcohol. The hydrogenation of the diketone benzil formed mainly the meso alcohol (meso:rac=3:1), whereas hexane-2,5-dione resulted in only rac-2,5-hexanediol. A 6:1 mixture of endo:exo norborneol resulted from the hydrogenation of norcamphor. Hydrogenation of benzaldehyde and valeraldehyde gave their respective alcohols.
Reaction SMILES: Cl[CH2:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([C:11]([F:14])([F:13])[F:12])=[CH:7][CH:6]=1)=[O:4].[CH:15]1([C:21](=O)[CH2:22][C:23]([O:25][CH2:26][CH3:27])=[O:24])[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]1>>[CH:15]1([C:21]2[O:4][C:3]([C:5]3[CH:10]=[CH:9][C:8]([C:11]([F:14])([F:13])[F:12])=[CH:7][CH:6]=3)=[CH:2][C:22]=2[C:23]([O:25][CH2:26][CH3:27])=[O:24])[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]1
Reactant: CCOC(=O)CC(=O)C1CCCCC1
Reactant: O=C(CCl)c1ccc(C(F)(F)F)cc1
Product: CCOC(=O)c1cc(-c2ccc(C(F)(F)F)cc2)oc1C1CCCCC1
Yield: 42.1 %

Procedure:
An operation similar to that in Example 1 (1) was performed using 2-chloro-4′-(trifluoromethyl)acetophenone (13.4 g) and ethyl 3-cyclohexyl-3-oxopropanoate (9.9 g) to give the title compound (7.7 g, 40%) as a yellow crystal.