Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Br:1][C:2]1[CH:9]=[CH:8][C:7]([O:10][Si:11]([C:24]([CH3:27])([CH3:26])[CH3:25])([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[CH:6][C:3]=1[CH:4]=[O:5].[BH4-].[Na+]>CO.C(Cl)Cl>[Br:1][C:2]1[CH:9]=[CH:8][C:7]([O:10][Si:11]([C:24]([CH3:25])([CH3:26])[CH3:27])([C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[CH:6][C:3]=1[CH2:4][OH:5]
Reactant: CC(C)(C)[Si](Oc1ccc(Br)c(C=O)c1)(c1ccccc1)c1ccccc1
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Solvent: ClCCl
Product: CC(C)(C)[Si](Oc1ccc(Br)c(CO)c1)(c1ccccc1)c1ccccc1
Reaction time: 2 h

Procedure:
The product from Example 1, Step A (8.87 g, 20.2 mmol) was dissolved in methanol (50 mL) and methylene chloride (20 mL). Sodium borohydride (764 mg, 20.2 mmol) was added in portions at 0° C., and the solution was stirred for 2 hours. The reaction was quenched by the addition of saturated aqueous ammonium chloride until hydrogen evolution ceased. The resulting suspension was concentrated in vacuo and then partitioned between methylene chloride (50 mL) and saturated aqueous sodium bicarbonate (50 mL). The layers were separated and the aqueous layer was extracted with methylene chloride (3×100 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo to provide the title product as a yellow oil which was sufficiently pure for use in the next step.
Reaction SMILES: N(C(OCC)=O)=NC(OCC)=O.[C:13]([SiH2:17][O:18][C:19]([CH3:38])([CH3:37])[C:20]1[CH:33]=[CH:32][CH:31]=[C:30]2[C:21]=1[S:22][C:23]1[C:24]([CH2:35]O)=[CH:25][CH:26]=[CH:27][C:28]=1[N:29]2[CH3:34])([CH3:16])([CH3:15])[CH3:14].[C:39]1(=[O:49])[NH:43][C:42](=[O:44])[C:41]2=[CH:45][CH:46]=[CH:47][CH:48]=[C:40]12.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>O1CCCC1>[C:13]([SiH2:17][O:18][C:19]([CH3:38])([CH3:37])[C:20]1[CH:33]=[CH:32][CH:31]=[C:30]2[C:21]=1[S:22][C:23]1[C:24]([CH2:35][N:43]3[C:39](=[O:49])[C:40]4[C:41](=[CH:45][CH:46]=[CH:47][CH:48]=4)[C:42]3=[O:44])=[CH:25][CH:26]=[CH:27][C:28]=1[N:29]2[CH3:34])([CH3:14])([CH3:16])[CH3:15]
Reactant: O=C1NC(=O)c2ccccc21
Reactant: CN1c2cccc(CO)c2Sc2c1cccc2C(C)(C)O[SiH2]C(C)(C)C
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: CN1c2cccc(CN3C(=O)c4ccccc4C3=O)c2Sc2c1cccc2C(C)(C)O[SiH2]C(C)(C)C
Reaction time: 3 h
Yield: 78.2 %

Procedure:
1.62 ml (10.34 mmol) of diethyl azodicarboxylate were slowly added dropwise while cooling with ice and under argon to a solution of 3.09 g (7.97 mmol) of [6-(tert-butyl-dimethyl-silanyloxymethyl)-10-methyl-phenothiazin-4-yl]-methanol, 1.76 g (11.9 mmol) of phthalimide and 2.30 g (8.75 mmol) of triphenylphosphine in 65 ml of tetrahydrofuran. The reaction mixture was stirred at 0° for 3 hours and then worked-up analogously to that described in Example 2.1.1.ea. The residue was chromatographed on 500 g of silica gel with toluene/ethyl acetate (19:1), whereupon, after crystallization from ethanol/ethyl acetate, 3.22 g (78.2%) of 2-[6-(tert-butyl-dimethyl-silanyloxymethyl)-10-methyl-phenothiazin-4-ylmethyl]-2,3-dihydro-1H-isoindole-1,3-dione were obtained as a light yellow solid of m.p. 195°-196°.
Reaction SMILES: [ClH:1].Cl.C([N:10]1[CH2:15][CH2:14][CH:13]([N:16]([CH2:18][CH2:19][CH2:20][OH:21])[CH3:17])[CH2:12][CH2:11]1)C1C=CC=CC=1.[H][H]>CO.[Pd]>[ClH:1].[ClH:1].[OH:21][CH2:20][CH2:19][CH2:18][N:16]([CH3:17])[CH:13]1[CH2:14][CH2:15][NH:10][CH2:11][CH2:12]1
Reactant: CN(CCCO)C1CCN(Cc2ccccc2)CC1
Reactant: [H][H]
Agent: [Pd]
Agent: Cl
Solvent: CO
Product: CN(CCCO)C1CCNCC1
Reaction time: 2 h
Yield: 183.4 %

Procedure:
42.8 g of 1-benzyl-4-[(3-hydroxypropyl)-methylamino]-piperidine-dihydrochloride are dissolved in 450 ml of methanol, combined with 5 g of 5% palladium-charcoal and hydrogenated at about 50° C. with hydrogen at 4-5 bar. The catalyst is filtered off, the methanol is distilled off and the residue is stirred in acetone. Ether is added, the mixture is left to stand for about two hours and then the crystals are suction filtered. 28.7 g of 4-[-(3-hydroxypropyl)-methylamino]-piperidine-dihydrochloride are obtained in the form of a solid.
Reaction SMILES: [C:1]([C:5]1[CH:6]=[CH:7][C:8]([NH:17]S(C2C=CC(C)=CC=2)(=O)=O)=[C:9]([CH:16]=1)/[CH:10]=[CH:11]/[C:12]([O:14][CH3:15])=[O:13])([CH3:4])([CH3:3])[CH3:2].ClC1C=C2C(C(CC(O)=O)=[C:34]([C:38]([C:40]3[CH:45]=[C:44]([CH3:46])[CH:43]=[CH:42][N:41]=3)=[O:39])N2)=CC=1>>[CH3:15][O:14][C:12](=[O:13])[CH2:11][C:10]1[C:9]2[C:8](=[CH:7][CH:6]=[C:5]([C:1]([CH3:2])([CH3:3])[CH3:4])[CH:16]=2)[NH:17][C:34]=1[C:38]([C:40]1[CH:45]=[C:44]([CH3:46])[CH:43]=[CH:42][N:41]=1)=[O:39]
Reactant: Cc1ccnc(C(=O)c2[nH]c3cc(Cl)ccc3c2CC(=O)O)c1
Reactant: COC(=O)/C=C/c1cc(C(C)(C)C)ccc1NS(=O)(=O)c1ccc(C)cc1
Product: COC(=O)Cc1c(C(=O)c2cc(C)ccn2)[nH]c2ccc(C(C)(C)C)cc12

Procedure:
The compound was prepared according to the procedure described in Example of 57 from methyl trans-5-tert-butyl-2-(p-toluenesulfonylamino)cinnamate (step 2) and 2-bromoacetyl-4-methylpyridine hydrobromide (Preparation is described in step 2 of Example 31).
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[C:20]2[C:19]3[CH:18]=[CH:17][CH:16]=[C:15]([O:21][CH2:22][C:23]([F:26])([F:25])[F:24])[C:14]=3[N:13]=[C:12](Cl)[C:11]=2[CH2:10][CH2:9]1.[NH2:28][CH2:29][CH2:30][CH2:31][OH:32]>>[CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[C:20]2[C:19]3[CH:18]=[CH:17][CH:16]=[C:15]([O:21][CH2:22][C:23]([F:26])([F:25])[F:24])[C:14]=3[N:13]=[C:12]([NH:28][CH2:29][CH2:30][CH2:31][OH:32])[C:11]=2[CH2:10][CH2:9]1
Reactant: NCCCO
Reactant: Cc1ccccc1N1CCc2c(Cl)nc3c(OCC(F)(F)F)cccc3c21
Product: Cc1ccccc1N1CCc2c(NCCCO)nc3c(OCC(F)(F)F)cccc3c21

Procedure:
1-(2-Methylphenyl)-4-chloro-6-β,β,β-trifluoroethoxy-2,3-dihydropyrrolo[3,2-c]quinoline(500 mg, 1.3 mmol) was dissolved in 3-amino-1-propanol(5.0 ml), and reacted at the same condition of Step 6 in the Example 30 to obtain 496 mg of desired compound as solid in 90% of yield.
Reaction SMILES: ClC1C=C([N+]([O-])=O)C(N)=NC=1.[F:12][C:13]([F:20])([CH:17]([F:19])[F:18])[C:14](Cl)=[O:15].[Cl:21][C:22]1[CH:23]=[C:24]([N+:30]([O-:32])=[O:31])[C:25]([NH2:29])=[N:26][C:27]=1[Cl:28].C(N(CC)CC)C>O1CCCC1>[Cl:21][C:22]1[CH:23]=[C:24]([N+:30]([O-:32])=[O:31])[C:25]([NH2:29])=[N:26][C:27]=1[Cl:28].[Cl:21][C:22]1[CH:23]=[C:24]([N+:30]([O-:32])=[O:31])[C:25]([NH:29][C:14](=[O:15])[C:13]([F:20])([F:12])[CH:17]([F:19])[F:18])=[N:26][C:27]=1[Cl:28]
Reactant: O=C(Cl)C(F)(F)C(F)F
Agent: Nc1nc(Cl)c(Cl)cc1[N+](=O)[O-]
Agent: Nc1ncc(Cl)cc1[N+](=O)[O-]
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: O=C(Nc1nc(Cl)c(Cl)cc1[N+](=O)[O-])C(F)(F)C(F)F
Yield: 94 %

Procedure:
5,6-Dichloro-2-amino-3-nitropyridine was prepared by chlorination of 5-chloro-2-amino-3-nitropyridine and was subsequently reacted with 2,2,3,3-tetrafluoropropionyl chloride. More particularly, 5,6-dichloro-2-amino-3-nitropyridine (3.0 grams; 0.15 mole) was taken up in tetrahydrofuran (20 ml.) and triethylamine (2 ml.) was added. Then 2,2,3,3-tetrafluoropropionyl chloride was added portionwise until all the starting material had reacted. The reaction yielded 5.3 grams (94 percent yield) of 5,6-dichloro-2-(2,2,3,3-tetrafluoropropionamido)-3-nitropyridine as an oil. Its identity was confirmed by infrared spectroscopy.
Reaction SMILES: [CH:1]([C:3]1[C:4]([CH3:24])=[CH:5][C:6]([CH3:23])=[C:7]([CH:22]=1)[C:8]([N:10]1[CH2:13][CH:12]([C:14]2[CH:21]=[CH:20][C:17]([C:18]#[N:19])=[CH:16][CH:15]=2)[CH2:11]1)=[O:9])=O.[O:25]1[CH2:30][CH2:29][N:28]([C:31]2[N:36]=[CH:35][C:34]([NH2:37])=[C:33]([NH2:38])[CH:32]=2)[CH2:27][CH2:26]1.C(=O)(O)[O-].[Na+]>C(O)C>[CH3:23][C:6]1[CH:5]=[C:4]([CH3:24])[C:3]([C:1]2[NH:37][C:34]3[CH:35]=[N:36][C:31]([N:28]4[CH2:29][CH2:30][O:25][CH2:26][CH2:27]4)=[CH:32][C:33]=3[N:38]=2)=[CH:22][C:7]=1[C:8]([N:10]1[CH2:11][CH:12]([C:14]2[CH:21]=[CH:20][C:17]([C:18]#[N:19])=[CH:16][CH:15]=2)[CH2:13]1)=[O:9]
Reactant: Nc1cnc(N2CCOCC2)cc1N
Reactant: Cc1cc(C)c(C(=O)N2CC(c3ccc(C#N)cc3)C2)cc1C=O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCO
Product: Cc1cc(C)c(-c2nc3cc(N4CCOCC4)ncc3[nH]2)cc1C(=O)N1CC(c2ccc(C#N)cc2)C1
Temperature: 70 °C
Reaction time: 72 h
Yield: 38.2 %

Procedure:
Into a 50-mL round-bottom flask, was placed a solution of 4-(1-(5-formyl-2,4-dimethylbenzoyl)azetidin-3-yl)benzonitrile (compound 151.4, 159 mg, 0.50 mmol) in ethanol (16 mL). 6-Morpholinopyridine-3,4-diamine (compound 151.2, 194 mg, 1.00 mmol) and NH4OAc (308 mg, 4.00 mmol) were added to the reaction. The reaction mixture was stirred for 3 days at 70° C. under air. The pH of the solution was adjusted to 8-9 with sodium bicarbonate (sat.). The reaction mixture was extracted with 1×100 mL of ethyl acetate. The organic layer was washed with 3×50 mL of brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crude product (200 mg) was purified by Prep-HPLC with the following conditions (1#-Pre-HPLC-010(Waters)): Column, SunFire Prep C18 OBD Column, 5 μm, 19*150 mm; mobile phase, WATER WITH 0.05% TFA and CH3CN (20.0% CH3CN up to 36.0% in 10 min, up to 100.0% in 1 min, down to 20.0% in 2 min); Detector, UV 254 and 220 nm. This resulted in 94.1 mg (38%) of the title compound as a brown solid. m/z (ES+) 493 (M+H)+.
Reaction SMILES: [C:1]([O:5][C:6]([C@H:8]1[CH2:12][N:11](C(OCC2C=CC=CC=2)=O)[C:10](=[O:23])[N:9]1[CH3:24])=[O:7])([CH3:4])([CH3:3])[CH3:2].[H][H]>CO.[Pd]>[C:1]([O:5][C:6]([C@H:8]1[CH2:12][NH:11][C:10](=[O:23])[N:9]1[CH3:24])=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: [H][H]
Reactant: CN1C(=O)N(C(=O)OCc2ccccc2)C[C@@H]1C(=O)OC(C)(C)C
Agent: [Pd]
Solvent: CO
Product: CN1C(=O)NC[C@@H]1C(=O)OC(C)(C)C
Reaction time: 15 h
Yield: 94 %

Procedure:
To a solution of (R)-3-methyl-2-oxoimidazolidine-1,4-dicarboxylic acid 1-benzyl ester 4-tert-butyl ester (167 mg) in methanol (1.7 ml) was added 10 wt % palladium on carbon at room temperature, and the mixture was stirred for 15 hours under one atom. of hydrogen. Under nitrogen atmosphere, this reaction solution was filtered through Celite, and eluted with methanol. The filtrate was concentrated under reduced pressure to give the titled compound (94 mg).
Reaction SMILES: [Cl:1][C:2]1[CH:30]=[CH:29][C:5]([CH2:6][NH:7][C:8]([C:10]2[CH:15]=[CH:14][C:13]([C:16]3[CH:21]=[C:20]([C:22]4[O:23][C:24]([CH3:27])=[N:25][N:26]=4)[CH:19]=[CH:18][C:17]=3[CH3:28])=[CH:12][CH:11]=2)=[O:9])=[CH:4][CH:3]=1.I[CH2:32][CH3:33]>>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][N:7]([CH2:32][CH3:33])[C:8]([C:10]2[CH:11]=[CH:12][C:13]([C:16]3[CH:21]=[C:20]([C:22]4[O:23][C:24]([CH3:27])=[N:25][N:26]=4)[CH:19]=[CH:18][C:17]=3[CH3:28])=[CH:14][CH:15]=2)=[O:9])=[CH:29][CH:30]=1
Reactant: Cc1nnc(-c2ccc(C)c(-c3ccc(C(=O)NCc4ccc(Cl)cc4)cc3)c2)o1
Reactant: CCI
Product: CCN(Cc1ccc(Cl)cc1)C(=O)c1ccc(-c2cc(-c3nnc(C)o3)ccc2C)cc1

Procedure:
N-(4-Chlorobenzyl)-N-ethyl-2′-methyl-5′-(5-methyl-1,3,4-oxadiazol-2-yl)-1,1′-biphenyl-4-carboxamide was prepared from N-(4-chlorobenzyl)-2′-methyl-5′-(5-methyl-1,3,4-oxadiazol-2-yl)-1,1′-biphenyl-4-carboxamide and iodoethane using method L. NMR; δH [2H6]—DMSO 7.89,(1H, d), 7.76,(1H, s), 7.58-7.42,(8H, m), 7.27,(1H, b), 4.69-4.53,(2H, m), 3.37-3.23,(2H, m), 2.55,(3H, s), 2.32,(3H, s), 1.06,(3H, b). LCMS; retention time 3.74 min, MH+ 446/448.
Reaction SMILES: Br[C:2]1[C:10]2[C:9]([NH2:11])=[N:8][CH:7]=[N:6][C:5]=2[N:4]([CH2:12][CH2:13][N:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)[CH:3]=1.CC1(C)C(C)(C)OB([C:28]2[CH:29]=[C:30]3[C:34](=[CH:35][CH:36]=2)[N:33]([C:37](=[O:49])[CH2:38][C:39]2[CH:44]=[CH:43][CH:42]=[C:41]([C:45]([F:48])([F:47])[F:46])[CH:40]=2)[CH2:32][CH2:31]3)O1.O1CCOCC1.C([O-])(O)=O.[Na+]>O.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>[N:14]1([CH2:13][CH2:12][N:4]2[C:5]3[N:6]=[CH:7][N:8]=[C:9]([NH2:11])[C:10]=3[C:2]([C:28]3[CH:29]=[C:30]4[C:34](=[CH:35][CH:36]=3)[N:33]([C:37](=[O:49])[CH2:38][C:39]3[CH:44]=[CH:43][CH:42]=[C:41]([C:45]([F:48])([F:46])[F:47])[CH:40]=3)[CH2:32][CH2:31]4)=[CH:3]2)[CH2:19][CH2:18][O:17][CH2:16][CH2:15]1
Reactant: Nc1ncnc2c1c(Br)cn2CCN1CCOCC1
Reactant: CC1(C)OB(c2ccc3c(c2)CCN3C(=O)Cc2cccc(C(F)(F)F)c2)OC1(C)C
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: C1COCCO1
Solvent: O
Product: Nc1ncnc2c1c(-c1ccc3c(c1)CCN3C(=O)Cc1cccc(C(F)(F)F)c1)cn2CCN1CCOCC1
Temperature: 100 °C
Yield: 41.5 %

Procedure:
To 5-bromo-7-[2-(4-morpholinyl)ethyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine (50 mg, 0.153 mmol) and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-{[3-(trifluoromethyl)phenyl]acetyl}-2,3-dihydro-1H-indole (93 mg, 0.215 mmol) were added 1,4-Dioxane (2 mL) and sat. NaHCO3 (1 mL) in a 5 ml sealable vessel. The mixture was then bubbled with N2 gas for 5 minutes then added Pd(Ph3P)4 (17.71 mg, 0.015 mmol) and the reaction was capped and heated at 100° C. overnight. The reaction was then diluted with water (2 ml) then extracted with EtOAc (3×3 ml). The organics were then combined and washed with brine, dried over MgSO4, filtered, and concentrated. The residue was dissolved in 3 mL of DMSO and then purified by HPLC: (HPLC condition: Gilson using Trilution software with a Sunfire 5u C18(2) 100A. 50×30.00 mm 5 micron. 7.3-minute run (47 ml/min, 18% ACN/H2O, 0.1% TFA to 43% ACN/H2O, 0.1% TFA) with UV detection at 220 nm). Product fractions were combined and the volume was reduced to remove most of the MeCN. To the water left behind was added saturated NaHCO3 and then the mixture was extracted with EtOAc (3×15 mL). The organics were combined, washed with saturated NaCl solution, dried over MgSO4, filtered and concentrated. Then the product was transferred into a 40 mL vial with MeCN then added water and freeze-dried to give 7-[2-(4-morpholinyl)ethyl]-5-(1-{[3-(trifluoromethyl)phenyl]acetyl}-2,3-dihydro-1H-indol-5-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine (35 mg, 41.5% yield) as a white solid. LC-MS (ES) m/z=551.5 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ 8.10-8.15 (m, 2H), 7.69 (s, 1H), 7.56-7.66 (m, 3H), 7.33 (s, 2H), 7.24 (d, J=8.34 Hz, 1H), 6.06 (br. s., 2H), 4.24-4.31 (m, 4H), 4.04 (s, 2H), 3.54 (br. s., 4H), 3.22-3.29 (m, J=7.83 Hz, 2H), 2.71 (br. s., 2H), 2.46 (br. s., 4H).
Reaction SMILES: Cl.CO.[OH:4][C:5]1[CH:21]=[CH:20][C:19]([OH:22])=[CH:18][C:6]=1[CH2:7][N:8]1[CH2:13][CH2:12][N:11]([C:14]([S:16][CH3:17])=[S:15])[CH2:10][CH2:9]1>O>[C:5]1(=[O:4])[CH:21]=[CH:20][C:19](=[O:22])[CH:18]=[C:6]1[CH2:7][N:8]1[CH2:9][CH2:10][N:11]([C:14]([S:16][CH3:17])=[S:15])[CH2:12][CH2:13]1
Reactant: CSC(=S)N1CCN(Cc2cc(O)ccc2O)CC1
Agent: Cl
Solvent: O
Solvent: CO
Product: CSC(=S)N1CCN(CC2=CC(=O)C=CC2=O)CC1
Reaction time: 0.17 h
Yield: 34.6 %

Procedure:
In a mixture of 6.8 ml of 1-N hydrochloric acid and 6.8 ml of methanol was dissolved 680 mg of methyl 4-(2,5-dihydroxybenzyl)-1-piperazinecarbodithioate. The resulting solutionwas chilled with ice, and to this was drowpise added a solution of 1.24 g (5.3 mmol.) of FeCl3.6H2O in 4.3 ml of water for 15 min. To this was further added 25 ml of methanol. To thus obtained homogeneous solution was again added a solution of 2.2 g of FeCl3.6H2O in 10 ml of water. The mixture was then stirred for 10 min. and placed under reduced pressure to distill off methanol. To the residue was added 50 ml of chloroform, and to this was added a saturated sodium hydrogen carbonateto adjust pH of the mixture to 7. Insolubles were removed by filtration. The organic solvent portion was taken out, washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and placed under reduced pressure to distill off the solvent. Theresidue was then purified by silica gel column chromatography to give 234 mg of the desired compound as a yellow powder, m.p. 115°-116° C. (decomp.), yield 38.9%.
Reaction SMILES: [I:1][C:2]1[CH:19]=[CH:18][C:5]([NH:6][C:7]2[S:8][C:9]3[N:17]=[CH:16][CH:15]=[CH:14][C:10]=3[C:11](=[O:13])[N:12]=2)=[CH:4][CH:3]=1.[H-].[Li+].[CH2:22](I)[CH2:23][CH3:24]>>[I:1][C:2]1[CH:19]=[CH:18][C:5]([N:6]=[C:7]2[N:12]([CH2:22][CH2:23][CH3:24])[C:11](=[O:13])[C:10]3[CH:14]=[CH:15][CH:16]=[N:17][C:9]=3[S:8]2)=[CH:4][CH:3]=1
Reactant: O=c1nc(Nc2ccc(I)cc2)sc2ncccc12
Reactant: CCCI
Agent: [H-]
Agent: [Li+]
Product: CCCn1c(=Nc2ccc(I)cc2)sc2ncccc2c1=O
Yield: 65.4 %

Procedure:
The reaction procedure of Example 11 was followed except that 900 mg (2.36 mmol) of 2-(4-iodoanilino)-4H-pyrido(3,2-e]-1,3-thiazin-4-one, 23 mg of lithium hydride and 482 mg of propyl iodide were used. The resulting residue was then purified through silica gel column chromatography (eluant: chloroform) to obtain 653 mg of 2-[(4-iodophenyl)imino]-2,3-dihydro-3-propyl-4H-pyrido[3,2-e]-1,3-thiazin-4-one (65%, recrystallized from a mixture of ether and hexane) as a low polarity substance and 40 mg of 2-[N-(4-iodophenyl)-N-propylamino]-4H-pyrido[3,2-e]-1,3-thiazin-4-one (4%, recrystallized from ether) as a high polarity substance.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6](=[O:11])[C:5]2([F:13])[F:12].[H-].[Na+].Br[CH2:17][C:18]([NH2:20])=[O:19].O>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:17][C:18]([NH2:20])=[O:19])[C:6](=[O:11])[C:5]2([F:13])[F:12]
Reactant: NC(=O)CBr
Reactant: O=C1Nc2ccc(Cl)cc2C1(F)F
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: NC(=O)CN1C(=O)C(F)(F)c2cc(Cl)ccc21
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
5-chloro-3,3-difluoro-1,3-dihydro-2H-indol-2-one 4 (2.55 g, 12.5 mmol) is dissolved in dry DMF (20 ml) under a nitrogen atmosphere. The solution is cooled at 0° C. and NaH (0.547 g, 13.8 mmol, 60% dispersion) is carefully added portionwise. When the nitrogen evolution ceases, bromoacetamide (2.05 g, 15.0 mmol) is added. After 30 minutes, the mixture is poured into cold water and the solid is filtered off and washed with water. The crude material is directly recrystallized in acetone/water affording of 2-(5-chloro-3,3-difluoro-2-oxo-2,3-dihydro-1H-indol-1-yl)acetamide 12 as a pink solid.
Reaction SMILES: Cl.[NH2:2][C:3]1[CH:11]=[C:10]([O:12][CH2:13][CH2:14][CH2:15][N:16]2[CH2:20][CH2:19][CH2:18][CH2:17]2)[C:9]([O:21][CH3:22])=[CH:8][C:4]=1[C:5]([NH2:7])=[O:6].[CH3:23]N(C=NC=[N+](C)C)C.[Cl-].O1CCOCC1.C([O-])(=O)C.[Na+]>C(O)(=O)C>[CH3:22][O:21][C:9]1[CH:8]=[C:4]2[C:3](=[CH:11][C:10]=1[O:12][CH2:13][CH2:14][CH2:15][N:16]1[CH2:20][CH2:19][CH2:18][CH2:17]1)[N:2]=[CH:23][NH:7][C:5]2=[O:6]
Reactant: COc1cc(C(N)=O)c(N)cc1OCCCN1CCCC1
Reactant: CN(C)C=NC=[N+](C)C
Agent: CC(=O)[O-]
Agent: Cl
Agent: [Cl-]
Solvent: C1COCCO1
Solvent: CC(=O)O
Product: COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCCC1
Temperature: 25 °C
Yield: 83.6 %

Procedure:
After repetition of the previous reaction, a mixture of 2-amino-5-methoxy-4-(3-pyrrolidin-1-ylpropoxy)benzamide hydrochloride (5.92 g), Gold's reagent (3.5 g) and dioxane (50 ml) was heated to reflux for 5 hours. Acetic acid (0.7 ml) and sodium acetate (1.33 g) were added and the reaction mixture was heated to reflux for a further 5 hours. The mixture was allowed to cool to ambient temperature and evaporated The residue was dissolved in water, adjusted to pH 8 with 2N aqueous sodium hydroxide solution and purified on a Diaion HP20SS resin column eluting with methanol (gradient 0-50%) in water. The fractions containing product were concentrated by evaporation and then freeze dried to give 6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)-3,4-dihydroquinazolin-4-one (4.55 g); NMR Spectrum: (DMSOd6 and CF3CO2D) 1.9 (m, 2H), 2.0-2.1 (m, 2H), 2.2-2.3 (m, 2H), 3.05 (m, 2H), 3.34 (t, 2M), 3.6-3.7 (br s, 2H), 3.94 (s, 3H), 4.27 (t, 2H), 7.31 (s, 1H), 7.55 (s, 1H), 9.02 (s, 1H).
Reaction SMILES: [C:1]1(C)C=CC=CC=1.[O:8]1[C:14]2(C)[CH:9]1[CH:10]1[C:16]([CH3:18])([CH3:17])[CH:11]1[CH2:12][CH2:13]2>CCOCC.[Zn+2].[Br-].[Br-]>[CH3:1][CH:9]1[CH:10]=[C:11]([CH:16]([CH3:17])[CH3:18])[CH2:12][CH2:13][C:14]1=[O:8]
Reactant: Cc1ccccc1
Reactant: CC12CCC3C(C1O2)C3(C)C
Agent: [Br-]
Agent: [Zn+2]
Solvent: CCOCC
Product: CC(C)C1=CC(C)C(=O)CC1

Procedure:
Approximately 20 mg of ZnBr2 (Fisher Certified-not fused) was added to 3 mL of toluene which had been distilled and stored over molecular sieves. The mixture was brought to reflux with vigorous stirring (to disperse the solid zinc bromide) in an apparatus which had been well flushed with nitrogen and equipped with a drying tube. Three quarters of a mixture of 2,3-epoxycarane (150 mg, 0.98 mmol) and 3 mL of toluene was added immediately. After 10 min the remaining one quarter was added over a 10 min period. Forty minutes after initial oxide addition the reaction mixture was cooled, taken up in 30 mL of ether, washed successively with water (2 × 10 mL), saturated NaHCO3 (1 × 10 mL), saturated NaCl (1 × 10 mL) and dried over anhydrous Na2SO4. Partial removal of solvent under reduced pressure afforded an oily residue from which 2-methyl-4-isopropylcyclohex-3-en-1-one (MICO) was isolated by preparative VPC. IR (CCl4) 2975, 1720, 1360, 1200, 1180(d), 970 and 930 reciprocal centimeters; UV (95% EtOH) lambda (max) 290 nm (extinction coefficient = 90.9); NMR (DCCl3) PPM 1.04 (d, 6H, J = 7 Hz, CH3 --C--CH3), 1.14 (d, 3H, J = 7 Hz, CH3 --C--), 2.3 (quintet, 1H, J = 7 Hz), 2.46 (n, M, 4H), 2.88 (br, Q with additional splitting H--C--C=O), 5.37 (n, M, 1H, H--C=C); MS m/e (rel. intensity) 153(4), 152(42), 135(5), 100(65), 109(10), 96(11), 95(100), 81(30), 68(10), 67(25), 55(11). Anal. calcd. for C10H16O: C, 78.89; H, 10.59. Found: C, 79.08; H, 10.41. An IR of the major product of the reaction showed a peak at 1720 reciprocal centimeters, attributed to the presence of a nonconjugated carbonyl. The product MICO exhibited a cool, refreshing menthol fragrance with a slight raspberry note which finds utility for the compound in odorant compositions.
Reaction SMILES: CN1CCN(C2C=CC(NC3C4N(N=CN=4)C(C4C=C(C(N)=O)SC=4)=CN=3)=CC=2)CC1.Br[C:33]1[N:38]2[N:39]=[CH:40][N:41]=[C:37]2[C:36]([NH:42][C:43]2[CH:48]=[CH:47][C:46]([O:49][CH2:50][CH2:51][N:52]3[CH2:57][CH2:56][O:55][CH2:54][CH2:53]3)=[CH:45][CH:44]=2)=[N:35][CH:34]=1.CC1(C)C(C)(C)OB([C:66]2[CH:67]=[C:68]3[C:72](=[CH:73][CH:74]=2)[C:71](=[O:75])[NH:70][CH2:69]3)O1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.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:55]1[CH2:56][CH2:57][N:52]([CH2:51][CH2:50][O:49][C:46]2[CH:47]=[CH:48][C:43]([NH:42][C:36]3[C:37]4[N:38]([N:39]=[CH:40][N:41]=4)[C:33]([C:66]4[CH:67]=[C:68]5[C:72](=[CH:73][CH:74]=4)[C:71](=[O:75])[NH:70][CH2:69]5)=[CH:34][N:35]=3)=[CH:44][CH:45]=2)[CH2:53][CH2:54]1
Reactant: CC1(C)OB(c2ccc3c(c2)CNC3=O)OC1(C)C
Reactant: Brc1cnc(Nc2ccc(OCCN3CCOCC3)cc2)c2ncnn12
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: CN1CCN(c2ccc(Nc3ncc(-c4csc(C(N)=O)c4)n4ncnc34)cc2)CC1
Agent: O=C([O-])[O-]
Solvent: C1COCCO1
Product: O=C1NCc2cc(-c3cnc(Nc4ccc(OCCN5CCOCC5)cc4)c4ncnn34)ccc21

Procedure:
This compound may be prepared using the methods as described for Compound 6, step 4, using (5-bromo-[1,2,4]triazolo[1,5-a]pyrazin-8-yl)-[4-(2-morpholin-4-yl-ethoxy)-phenyl]-amine (80 mg, 0.19 mmol), 5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-2,3-dihydro-isoindol-1-one (74 mg, 0.29 mmol), and Pd(PPh3)4 (55 mg, 0.047 mmol) in 1.5M Na2CO3 (1.02 mL, 1.53 mmol) and dioxane (3 mL). The reaction mixture is purified by silica gel column chromatography eluting with DCM and a 97:3 mixture DCM:NH3 (7M in MeOH). After trituration using diethyl ether, the title compound is isolated as a solid (61.9 mg, 69%). Conversion of the material into the mesylate salt, using 1M methanesulfonic acid (0.134 mL) in MeOH, affords the title compound (57.1 mg). 1H-NMR (400 MHz, d6-DMSO) δ(ppm) 2.40 (3H, s, MsOH), 3.25-3.38 (2H, m), 3.60-3.78 (4H, m), 3.84 (2H, t), 4.09 (2H, d), 4.45 (2H, m), 4.56 (2H, s), 7.14 (2H, d), 7.90 (1H, d), 8.05-8.19 (4H, m), 8.28 (1H, s), 8.76 (1H, br s), 8.79 (1H, s), 10.00 (1H, br s), 10.16 (1H, s). LCMS: Rt 1.98 min (99.1%), m/z (APCI) 472 (M+H)+.