Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][CH2:2][C:3]1[CH:4]=[C:5]([C:9]2[CH:18]=[CH:17][C:16]3[N:15]=[CH:14][C:13]4[N:19]([CH3:30])[C:20](=[O:29])[N:21]([C:22]5[C:23]([CH3:28])=[N:24][N:25]([CH3:27])[CH:26]=5)[C:12]=4[C:11]=3[CH:10]=2)[CH:6]=[N:7][CH:8]=1.CCN(C(C)C)C(C)C.[C:40](Cl)(=[O:42])[CH3:41]>ClCCl>[CH3:27][N:25]1[CH:26]=[C:22]([N:21]2[C:12]3[C:11]4[CH:10]=[C:9]([C:5]5[CH:4]=[C:3]([CH2:2][NH:1][C:40](=[O:42])[CH3:41])[CH:8]=[N:7][CH:6]=5)[CH:18]=[CH:17][C:16]=4[N:15]=[CH:14][C:13]=3[N:19]([CH3:30])[C:20]2=[O:29])[C:23]([CH3:28])=[N:24]1
Reactant: CC(=O)Cl
Reactant: Cc1nn(C)cc1-n1c(=O)n(C)c2cnc3ccc(-c4cncc(CN)c4)cc3c21
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CC(=O)NCc1cncc(-c2ccc3ncc4c(c3c2)n(-c2cn(C)nc2C)c(=O)n4C)c1
Reaction time: 0.75 h

Procedure:
To a mixture of 8-(5-aminomethyl-pyridin-3-yl)-1-(1,3-dimethyl-1H-pyrazol-4-yl)-3-methyl-1,3-dihydro-imidazo[4,5-c]quinolin-2-one (Example 230, 0.053 mmol) and Hünig's base (0.014 ml) in dichloromethane (1 ml) was added acetyl chloride (Aldrich, Buchs, Switzerland, 0.058 mmol). The RM was stirred for 45 min at it then evaporated to dryness. The residue was taken in MeOH and purified by preparative HPLC. The fractions containing product were basified with NaHCO3, concentrated and extracted with dichloromethane (2×). The combined organic layers were washed with brine, dried over Na2SO4, filtered, evaporated and dried under vacuum to give the title compound as a white solid. (HPLC: tR 1.95 min (Method A); M+H=442 MS-ES; 1H-NMR (d6-DMSO, 400 MHz) 8.99 (s, 1H), 8.56-8.53 (m, 1H), 8.48-8.46 (m, 1H), 8.40 (t, 1H), 8.16-8.12 (m, 2H), 7.94-7.90 (m, 1H), 7.78-7.75 (m, 1H), 7.58-7.56 (m, 1H), 4.38-4.27 (m, 2H), 3.92 (s, 3H), 3.58 (s, 3H), 1.95 (s, 3H), 1.89 (s, 3H))
Reaction SMILES: Cl[CH2:2][C:3]([NH:5][C:6]1[CH:27]=[CH:26][C:9]2[N:10]=[C:11]([NH:14][CH:15]3[C:23]4[C:18](=[CH:19][CH:20]=[CH:21][C:22]=4[O:24][CH3:25])[CH2:17][CH2:16]3)[O:12][CH2:13][C:8]=2[CH:7]=1)=[O:4].[NH:28]1[CH2:33][CH2:32][O:31][CH2:30][CH2:29]1>C(#N)C>[CH3:25][O:24][C:22]1[CH:21]=[CH:20][CH:19]=[C:18]2[C:23]=1[CH:15]([NH:14][C:11]1[O:12][CH2:13][C:8]3[CH:7]=[C:6]([NH:5][C:3](=[O:4])[CH2:2][N:28]4[CH2:33][CH2:32][O:31][CH2:30][CH2:29]4)[CH:27]=[CH:26][C:9]=3[N:10]=1)[CH2:16][CH2:17]2
Reactant: C1COCCN1
Reactant: COc1cccc2c1C(NC1=Nc3ccc(NC(=O)CCl)cc3CO1)CC2
Solvent: CC#N
Product: COc1cccc2c1C(NC1=Nc3ccc(NC(=O)CN4CCOCC4)cc3CO1)CC2
Yield: 97.3 %

Procedure:
Prepared from the above described rac-2-chloro-N-[2-(7-methoxy-indan-1-ylamino)-4H-benzo[d][1,3]oxazin-6-yl]-acetamide (100 mg, 0.259 mmol) and morpholine (226 ul, 2.59 mmol) in acetonitrile (1 ml) according to the procedure described for Example 3 step B. Obtained the title compound as an off-white foam (110 mg, 97%), MS (ISP) m/e=437.2 [(M+H)+].
Reaction SMILES: [CH3:1][C:2]1[O:6][C:5]([C:7]2[CH:12]=[CH:11][C:10]([C:13]([F:16])([F:15])[F:14])=[CH:9][CH:8]=2)=[N:4][C:3]=1[CH2:17][CH2:18][OH:19].O[C:21]1[C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[C:24]([CH:31]=[O:32])=[CH:23][CH:22]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>C1(C)C=CC=CC=1>[CH3:1][C:2]1[O:6][C:5]([C:7]2[CH:8]=[CH:9][C:10]([C:13]([F:16])([F:15])[F:14])=[CH:11][CH:12]=2)=[N:4][C:3]=1[CH2:17][CH2:18][O:19][C:21]1[C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[C:24]([CH:31]=[O:32])=[CH:23][CH:22]=1
Reactant: O=Cc1ccc(O)c2ccccc12
Reactant: Cc1oc(-c2ccc(C(F)(F)F)cc2)nc1CCO
Agent: CC(C)OC(=O)/N=N/C(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: Cc1ccccc1
Product: Cc1oc(-c2ccc(C(F)(F)F)cc2)nc1CCOc1ccc(C=O)c2ccccc12
Reaction time: 2 h

Procedure:
2.00 g of 2-[5-Methyl-2-(4-trifluoromethyl-phenyl)-oxazol-4-yl]-ethanol (7.37 mmol) was dissolved in 37 ml of toluene and treated successively at 0° C. with 1.27 g of 4-hydroxy-naphthalene-1-carbaldehyde (7.37 mmol), 1.93 g of triphenylphosphine (7.37 mmol), and 1.49 g (7.37 mmol) of DIAD. The cooling bath was then removed and stirring continued for 2 h. The reaction mixture was then evaporated to dryness in vacuo. Flash chromatography (SiO2, hexane/AcOEt=75/25), followed by boiling up in ether, delivered 1.28 g of the title compound as off-white crystals.
Reaction SMILES: [NH2:1][C:2]1[O:3][CH2:4][C@@:5]2([N:22]=1)[C:18]1[CH:17]=[C:16](O)[CH:15]=[C:14]([F:20])[C:13]=1[O:12][C:11]1[C:6]2=[CH:7][C:8](Br)=[CH:9][CH:10]=1.[C:23]([C:26]1[CH:27]=[C:28](B(O)O)[CH:29]=[N:30][CH:31]=1)#[C:24][CH3:25].[CH3:35][N:36]1[CH:40]=[C:39](B2OC(C)(C)C(C)(C)O2)[CH:38]=[N:37]1>>[F:20][C:14]1[C:13]2[O:12][C:11]3[C:6](=[CH:7][C:8]([C:28]4[CH:29]=[N:30][CH:31]=[C:26]([C:23]#[C:24][CH3:25])[CH:27]=4)=[CH:9][CH:10]=3)[C@@:5]3([CH2:4][O:3][C:2]([NH2:1])=[N:22]3)[C:18]=2[CH:17]=[C:16]([C:39]2[CH:38]=[N:37][N:36]([CH3:35])[CH:40]=2)[CH:15]=1
Reactant: NC1=N[C@@]2(CO1)c1cc(Br)ccc1Oc1c(F)cc(O)cc12
Reactant: CC#Cc1cncc(B(O)O)c1
Reactant: Cn1cc(B2OC(C)(C)C(C)(C)O2)cn1
Product: CC#Cc1cncc(-c2ccc3c(c2)[C@@]2(COC(N)=N2)c2cc(-c4cnn(C)c4)cc(F)c2O3)c1

Procedure:
The titled compound was synthesized by steps analogous to those described in method AA8 above, but using (S)-2-amino-7′-bromo-4′-fluoro-5H-spiro[oxazole-4,9′-xanthen]-2′-ol (prepared by steps analogous to those described in Method BB40 and Example 2), 5-(prop-1-ynyl)pyridin-3-ylboronic acid, and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole.
Reaction SMILES: [Cl:1][C:2]1[S:3][C:4]([CH2:7][N:8]2[CH2:12][CH2:11][NH:10][C:9]2=[CH:13][N+:14]([O-:16])=[O:15])=[CH:5][N:6]=1.[CH:17](=[O:22])[CH2:18][CH2:19][CH:20]=O.Cl>C(#N)C>[Cl:1][C:2]1[S:3][C:4]([CH2:7][N:8]2[C:9]3=[C:13]([N+:14]([O-:16])=[O:15])[CH:20]4[O:22][CH:17]([N:10]3[CH2:11][CH2:12]2)[CH2:18][CH2:19]4)=[CH:5][N:6]=1
Reactant: O=CCCC=O
Reactant: O=[N+]([O-])C=C1NCCN1Cc1cnc(Cl)s1
Agent: Cl
Solvent: CC#N
Product: O=[N+]([O-])C1=C2N(Cc3cnc(Cl)s3)CCN2C2CCC1O2
Temperature: 25 °C
Yield: 63 %

Procedure:
To a 50 ml round bottom flask was added 1.30 g (0.005 mol) 1-((2-chlorothiazol-5-yl)methyl)-2-(nitromethylene)imidazolidine, 30 ml dry acetonitrile, 0.860 g (0.01 mol) succinaldehyde and catalytic concentrated HCl. The reaction was stirred at r.t. and monitored by TLC. After completion, the mixture was evaporated to remove solvent and purified by column chromatography to afford final product as faint yellow powder with 63% yield.
Reaction SMILES: [N:1]1([CH2:7][C@@H:8]([OH:11])[CH2:9][OH:10])[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[S:12](Cl)([Cl:14])=[O:13]>C(Cl)Cl>[ClH:14].[O:13]=[S:12]1[O:11][C@H:8]([CH2:7][N:1]2[CH2:6][CH2:5][O:4][CH2:3][CH2:2]2)[CH2:9][O:10]1
Reactant: OC[C@H](O)CN1CCOCC1
Reactant: O=S(Cl)Cl
Solvent: ClCCl
Product: Cl
Product: O=S1OC[C@@H](CN2CCOCC2)O1
Temperature: 25 °C
Yield: 103.7 %

Procedure:
To a solution of (2R)-3-(4-morpholinyl)-1,2-propanediol (0.447 g, 2.77 mmol) in CH2Cl2 (7.5 mL) was cooled to 0° C. and added thionyl chloride (0.41 mL, 5.55 mmol, 2.0 equiv.) was added dropwise. The resulting solution was heated at the reflux temperature for 1 hr, cooled to room temperature and concentrated under reduced pressure to give 4-[(4R)-(2-oxido-1,3,2-dioxathiolan-4-yl)methyl]morpholine hydrochloride (0.70 g, 104%). This material was used in the next step without further purification.
Reaction SMILES: Cl[C:2]1[N:7]2[C:8]([CH2:11][CH2:12][CH3:13])=[N:9][CH:10]=[C:6]2[CH:5]=[C:4]([Cl:14])[N:3]=1.[NH3:15]>>[NH2:15][C:2]1[N:7]2[C:8]([CH2:11][CH2:12][CH3:13])=[N:9][CH:10]=[C:6]2[CH:5]=[C:4]([Cl:14])[N:3]=1
Reactant: CCCc1ncc2cc(Cl)nc(Cl)n12
Reactant: N
Product: CCCc1ncc2cc(Cl)nc(N)n12

Procedure:
Using the method of Example 39, 5,7-dichloro-3-(n-propyl)imidazo[1,5-c]pyrimidine (from Example 36) was reacted with ammonia to provide white solid 5-amino-7-chloro-3-(n-propyl)imidazo[1,5-c]pyrimidine, m.p. 160°-161° C. (dec.). Analysis: Calculated for C9H11ClN4 : %C, 51.3; %H, 5.3; %N, 26.6; Found %C, 51.5; %H, 5.2; %N, 26.9.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][S:9]([NH-:12])(=[O:11])=[O:10])=[CH:4][CH:3]=1.Cl[C:14]1[CH:19]=[C:18]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=2[O:26][CH2:27][CH3:28])[N:17]=[CH:16][N:15]=1>CN(C=O)C>[CH2:27]([O:26][C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=1[C:18]1[N:17]=[CH:16][N:15]=[C:14]([NH:1][C:2]2[CH:7]=[CH:6][C:5]([CH2:8][S:9]([NH2:12])(=[O:10])=[O:11])=[CH:4][CH:3]=2)[CH:19]=1)[CH3:28]
Reactant: [NH-]S(=O)(=O)Cc1ccc(N)cc1
Reactant: CCOc1ccccc1-c1cc(Cl)ncn1
Solvent: CN(C)C=O
Product: CCOc1ccccc1-c1cc(Nc2ccc(CS(N)(=O)=O)cc2)ncn1
Temperature: 80 °C

Procedure:
A mixture of (4-aminophenyl)methanesulfonyl amide (0.093 g, 0.50 mmol) and 4-chloro-6-(2-ethoxyphenyl)-pyrimidine (0.117 g, 0.50 mmol) in DMFA (3 mL) was stirred at 80° C. till the reaction completion (TLC control). Then the reaction mixture was concentrated in vacuo and the residue recrystallized from isopropanol to give {4-[6-(2-ethoxy-phenyl)-pyrimidin-4-ylamino]-phenyl}-methanesulfonamide (Compound 6)
Reaction SMILES: [CH3:1][C:2]1([CH3:23])[O:7][C:6]2[CH:8]=[C:9]([CH2:13][CH2:14][CH2:15][CH2:16][CH3:17])[CH:10]=[C:11]([OH:12])[C:5]=2[C@@H:4]2[CH:18]=[C:19]([CH3:22])[CH2:20][CH2:21][C@@H:3]12.Br[CH:25]([CH2:31][CH3:32])[C:26]([O:28]CC)=[O:27].C(=O)([O-])[O-].[K+].[K+]>CS(C)=O>[CH3:23][C:2]1([CH3:1])[O:7][C:6]2[CH:8]=[C:9]([CH2:13][CH2:14][CH2:15][CH2:16][CH3:17])[CH:10]=[C:11]([O:12][CH2:32][CH2:31][CH2:25][C:26]([OH:28])=[O:27])[C:5]=2[C@@H:4]2[CH:18]=[C:19]([CH3:22])[CH2:20][CH2:21][C@@H:3]12
Reactant: CCCCCc1cc(O)c2c(c1)OC(C)(C)[C@@H]1CCC(C)=C[C@@H]21
Reactant: CCOC(=O)C(Br)CC
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CS(C)=O
Product: CCCCCc1cc(OCCCC(=O)O)c2c(c1)OC(C)(C)[C@@H]1CCC(C)=C[C@@H]21
Temperature: 25 °C
Reaction time: 8 h
Yield: 88 %

Procedure:
A solution of 1.0 g (3.18 mmol) of (6aR,10aR)-6a,7,8,10a-tetrahydro-6,6,9-trimethyl-3-pentyl-6H-dibenzo[b,d]pyran-1-ol and 2.32 ml of ethyl bromobutyrate in 10 ml of dimethylsulfoxide was degassed, 1.39 g of potassium carbonate was added, the mixture was degassed and then stirred at room temperature under argon overnight. The reaction was diluted with 250 ml of water and extracted with ether. The extracts were concentrated under vacuum, and the residue was dissolved in benzene and chromatographed over silica gel. The fractions containing the intermediate ester were combined and concentrated under vacuum. The residue was mixed with 60 ml of methanol, 12 ml of water and 1.30 g of sodium carbonate, and the mixture was heated under reflux for 3 hrs. The methanol was evaporated under vacuum, and the residue was acidified with hydrochloric acid and extracted with dichloromethane. The extracts were dried and concentrated, and the residue was dissolved in hexane and chromatographed over silica gel. Elution with from 5 through 20% ethyl acetate in benzene gave fractions containing product which were combined and concentrated to give 1.12 g (88%) of (6aR-trans)-4-[(6a,7,8,10a-Tetrahydro-6,6,9-trimethyl-3-pentyl-6H-dibenzo[b,d]pyran-1-yl)oxy]butanoic acid as a colorless oil: ir (CHCl3) 1740 and 1715 cm-1 ; uv max (C2H5OH) 225 nm (infl) (ε13,000), 275 (2600), and 281 (2700); nmr (CDCl3) δ9.7 (br, CO2H), 6.28 and 6.22 [d, (H-2 and H-4) which includes m~6.25, H-10], 4.02 (t, OCH2C), 3.16 (m, H-10a), 2.63 (t, ArCH2C), 2.47 (t, COCH2C), 1.63 (s, 9-CH3), 1.37 and 1.04 (two s, 6,6-diCH3), and 0.86 (t, ω-CH3); mass mol wt 400; [α]C25° -122.6° (c 1.003, CHCl3).
Reaction SMILES: [CH3:1][O:2][C@@H:3]([C@@H:33]([N:38]([CH3:46])[C:39](=[O:45])[C@H:40]([CH:42]([CH3:44])[CH3:43])[NH2:41])[C@@H:34]([CH3:37])[CH2:35][CH3:36])[CH2:4][C:5]([N:7]1[CH2:11][CH2:10][CH2:9][C@H:8]1[C@H:12]([O:31][CH3:32])[C@@H:13]([CH3:30])[C:14](=[O:29])[NH:15][C@H:16]([C:24]1[S:25][CH:26]=[CH:27][N:28]=1)[CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[O:6].[C:47]([O:51][C:52]([N:54]1[CH2:59][CH2:58][CH2:57][CH2:56][C@@:55]1([CH3:63])[C:60](O)=[O:61])=[O:53])([CH3:50])([CH3:49])[CH3:48].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C>ClCCl>[CH3:1][O:2][C@@H:3]([C@@H:33]([N:38]([CH3:46])[C:39](=[O:45])[C@@H:40]([NH:41][C:60]([C@:55]1([CH3:63])[CH2:56][CH2:57][CH2:58][CH2:59][N:54]1[C:52]([O:51][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:53])=[O:61])[CH:42]([CH3:44])[CH3:43])[C@@H:34]([CH3:37])[CH2:35][CH3:36])[CH2:4][C:5]([N:7]1[CH2:11][CH2:10][CH2:9][C@H:8]1[C@H:12]([O:31][CH3:32])[C@@H:13]([CH3:30])[C:14](=[O:29])[NH:15][C@H:16]([C:24]1[S:25][CH:26]=[CH:27][N:28]=1)[CH2:17][C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1)=[O:6]
Reactant: CC[C@H](C)[C@@H]([C@@H](CC(=O)N1CCC[C@H]1[C@H](OC)[C@@H](C)C(=O)N[C@@H](Cc1ccccc1)c1nccs1)OC)N(C)C(=O)[C@@H](N)C(C)C
Reactant: CC(C)(C)OC(=O)N1CCCC[C@@]1(C)C(=O)O
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CC[C@H](C)[C@@H]([C@@H](CC(=O)N1CCC[C@H]1[C@H](OC)[C@@H](C)C(=O)N[C@@H](Cc1ccccc1)c1nccs1)OC)N(C)C(=O)[C@@H](NC(=O)[C@]1(C)CCCCN1C(=O)OC(C)(C)C)C(C)C
Yield: 62.3 %

Procedure:
According to the general procedure D, from #86 (280 mg, 0.4 mmol, 1 eq.), #156 (100 mg, 0.4 mmol, 1 eq.), dichloromethane (5 mL), HATU (182 mg, 0.48 mmol, 1.2 eq.) and N,N-diisopropylethylamine (100 mg, 0.8 mmol, 2 eq.) was synthesized the crude desired material, which was purified by silica gel chromatography (Gradient: 0.01 to 0.05% methanol in dichloromethane) to afford #187 (220 mg, 62%) as a white solid. HPLC (Protocol V): m/z 883.57 [M+H+], retention time=3.23 minutes (purity=95%).
Reaction SMILES: C([O:5][C:6]([C:8]1[C:16]2[CH2:15][CH2:14][N:13]([C@H:17]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[CH3:18])[C@@H:12]([CH2:25][NH2:26])[C:11]=2[S:10][C:9]=1[NH2:27])=[O:7])(C)(C)C.[O:28]([C:35]1[CH:42]=[CH:41][C:38]([CH:39]=O)=[CH:37][CH:36]=1)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1.[BH4-].[Na+].C(N(C(C)C)CC)(C)C.[C:54](Cl)(=[O:56])[CH3:55]>C(O)C.ClCCl>[C:54]([N:26]([CH2:25][C@H:12]1[C:11]2[S:10][C:9]([NH2:27])=[C:8]([C:6]([OH:5])=[O:7])[C:16]=2[CH2:15][CH2:14][N:13]1[C@H:17]([C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1)[CH3:18])[CH2:39][C:38]1[CH:41]=[CH:42][C:35]([O:28][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)=[CH:36][CH:37]=1)(=[O:56])[CH3:55]
Reactant: C[C@@H](c1ccccc1)N1CCc2c(sc(N)c2C(=O)OC(C)(C)C)[C@@H]1CN
Reactant: O=Cc1ccc(Oc2ccccc2)cc1
Reactant: CC(=O)Cl
Agent: [BH4-]
Agent: [Na+]
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Solvent: CCO
Product: CC(=O)N(Cc1ccc(Oc2ccccc2)cc1)C[C@H]1c2sc(N)c(C(=O)O)c2CCN1[C@@H](C)c1ccccc1
Temperature: 0 °C
Reaction time: 1 h
Yield: 44.6 %

Procedure:
A solution of 2-amino-7-(S)-aminomethyl-6-(1-(S)-phenyl-ethyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid tert-butyl ester (500 mg, 1.29 mmol) and 4-phenoxybenzaldehyde (256 mg, 1.29 mmol) was heated to 50° C. in ethanol (50 ml) for 1 hour in the presence of molecular sieves (4 A, 5 ml). The reaction mixture was cooled on an ice bath before sodium borohydride (98 mg, 2.59 mmol) was added in three portions over 45 min. The cooling bath was removed and the reaction mixture was allowed to reach room temperature. The mixture was filtered through a plug of Celite and the filter cage was washed with dichloromethane (3×25 ml). The solvent was removed in vacuo and the residue was redissolved in ethyl acetate (50 ml), washed with sodium bicarbonate (50 ml) and dried (MgSO4). The solvent was removed in vacuo before the product was dissolved in dichloromethane (10 ml). The solution was cooled on an ice bath before di-isopropyl-ethyl amine (101 mg, 1.29 mmol) was added followed by drop wise addition of acetyl chloride (101 mg, 1.29 mmol) in dichloromethane (1 ml). The reaction mixture was stirred 1 hour at 0° C. and the solution was washed with sodium bicarbonate (10 ml) and dried (MgSO4). The crude product was purified by flash column chromatography (SiO2, ethyl acetate-petrol ether 1:3) to give 320 mg (41%) of 7-(S)-((acetyl-(4-phenoxy-benzyl)amino)methyl)-2-amino-6-(1-(S)-phenyl-ethyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid
Reaction SMILES: C([O:4][C:5]1[CH:14]=[C:13]2[C:8]([CH:9]=[CH:10][C:11]([C:15]([O:17][CH2:18][CH3:19])=[O:16])=[CH:12]2)=[CH:7][CH:6]=1)C=C.C(N(CC)[C:23]1[CH:28]=CC=C[CH:24]=1)C.Cl>>[CH2:28]([C:14]1[C:5]([OH:4])=[CH:6][CH:7]=[C:8]2[C:13]=1[CH:12]=[C:11]([C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH:10]=[CH:9]2)[CH:23]=[CH2:24]
Reactant: CCN(CC)c1ccccc1
Reactant: C=CCOc1ccc2ccc(C(=O)OCC)cc2c1
Agent: Cl
Product: C=CCc1c(O)ccc2ccc(C(=O)OCC)cc12

Procedure:
Ethyl 7-allyloxynaphthalene-2-carboxylate (6.2 g) was heated in refluxing N,N-diethylaniline for 2 hours. The solution was cooled, treated with dilute hydrochloric acid and extracted with ethyl acetate, which was then washed with dilute hydrochloric acid, and water, dried and evaporated to a solid. Crystallisation from benzene/petroleum ether (b.p. 40-60) afforded ethyl 8-allyl-7-hydroxynaphthalene-2-carboxylate (4.5 g), m.p. 115°-116°.
Reaction SMILES: [F:1][C:2]1[CH:27]=[C:26]([S:28]([CH3:31])(=[O:30])=[O:29])[CH:25]=[CH:24][C:3]=1[CH2:4][O:5][CH2:6][C@@H:7]1[CH2:9][C@@H:8]1[CH:10]1[CH2:15][CH2:14][N:13]([C:16]2[N:21]=[CH:20][C:19]([CH2:22][OH:23])=[CH:18][N:17]=2)[CH2:12][CH2:11]1.[H-].[Na+].[CH3:34]I>C(#N)C.CCOC(C)=O>[F:1][C:2]1[CH:27]=[C:26]([S:28]([CH3:31])(=[O:30])=[O:29])[CH:25]=[CH:24][C:3]=1[CH2:4][O:5][CH2:6][C@@H:7]1[CH2:9][C@@H:8]1[CH:10]1[CH2:11][CH2:12][N:13]([C:16]2[N:21]=[CH:20][C:19]([CH2:22][O:23][CH3:34])=[CH:18][N:17]=2)[CH2:14][CH2:15]1
Reactant: CS(=O)(=O)c1ccc(COC[C@@H]2C[C@@H]2C2CCN(c3ncc(CO)cn3)CC2)c(F)c1
Reactant: CI
Agent: [H-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CC#N
Product: COCc1cnc(N2CCC([C@H]3C[C@H]3COCc3ccc(S(C)(=O)=O)cc3F)CC2)nc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
The product of step A (20 mg, 0.044 mmol) was dissolved in acetonitrile (4 mL) at RT under N2 and sodium hydride (10 mg of a 60% dispersion in oil, 0.25 mmol) was added followed by CH3I (31.6 mg, 0.222 mmol). The mixture was stirred at RT overnight. The mixture was diluted with EtOAc, washed with sat. NH4Cl, dried over MgSO4, filtered and evaporated in vacuo. The crude material was purified by preparative thin-layer chromatography (70% EtOAc in hexane) to yield the title compound. 1H NMR (500 MHz, CDCl3) δ 8.30 (s, 2H), 7.78 (dd, 1H), 7.73 (m, 1H), 7.67 (dd, 1H), 4.80-4.64 (m, 4H), 4.28 (s, 2H), 3.71 (dd, 1H), 3.61-3.54 (m, 1H), 3.37 (s, 3H), 3.08 (s, 3H), 2.93-2.80 (m, 2H), 1.96 (d, 1H), 1.85 (d, 1H), 1.43-1.22 (m, 3H), 1.15-1.04 (m, 1H), 0.94-0.71 (m, 2H), 0.12-0.08 (m, 1H). MS (ESI) m/z 464 [M+H]+. GPR119 Human EC50: 1.6 nM
Reaction SMILES: Cl[C:2]1[C:7](C2C=CC=CC=2)=[CH:6][CH:5]=[CH:4][N:3]=1.[NH:14]1[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]1.[CH:20]([OH:23])(C)C>>[CH3:20][O:23][C:7]1[C:2]([N:14]2[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]2)=[N:3][CH:4]=[CH:5][CH:6]=1
Reactant: C1CNCCN1
Reactant: CC(C)O
Reactant: Clc1ncccc1-c1ccccc1
Product: COc1cccnc1N1CCNCC1

Procedure:
The 2-chloro-3-methoxypyridine (VI) was treated with piperazine in a refluxing isopropanol medium according to the procedure of Example 3 and, following a similar work-up, gave the desired IIIc intermediate.
Reaction SMILES: [C:1](#[N:5])[CH2:2][C:3]#[N:4].[CH2:6]([N:10]([CH2:15]CCC)CCCC)[CH2:7]CC.ClCC(Cl)=[O:22].CN>CN(C)C=O>[NH2:4][C:3]1[N:10]([CH3:15])[CH2:6][C:7](=[O:22])[C:2]=1[C:1]#[N:5]
Reactant: N#CCC#N
Reactant: CCCCN(CCCC)CCCC
Reactant: O=C(Cl)CCl
Agent: CN
Solvent: CN(C)C=O
Product: CN1CC(=O)C(C#N)=C1N
Temperature: 0 °C
Reaction time: 0.17 h

Procedure:
99 g of malononitrile were dissolved in 150 ml of N,N-dimethylformamide (DMF) and cooled to 0° C. While cooling, 556 g of tributylamine and 169.5 g of chloroacetyl chloride were simultaneously added dropwise to this, and the mixture was then stirred at 10° C. for 10 minutes. The reaction mixture was subsequently added to a mixture of 1.5 kg of ice and 327 ml of 40% by weight aqueous methylamine solution and stirred at room temperature for 8 hours. The precipitate was filtered off with suction, washed and dried in an oven at 50° C. 124 g (60% of theory) of the compound of the formula ##STR22## of melting point 300° C. were obtained. The IR, NMR, UV and mass spectra and the elemental analysis are consistent with the structural formula.
Reaction SMILES: [N+:1]([C:4]1[CH:44]=[CH:43][C:7]([CH2:8][O:9][C:10](=[O:42])[CH:11](N2C(SSC3SC4C=CC=CC=4N=3)C(NC(=O)COC3C=CC=CC=3)C2=O)[C:12](=[CH2:14])[CH3:13])=[CH:6][CH:5]=1)([O-:3])=[O:2]>CC(C)=O.O.C1(C)C=CC(S([O-])=O)=CC=1.[Ag+]>[N+:1]([C:4]1[CH:5]=[CH:6][C:7]([CH2:8][O:9][C:10](=[O:42])[CH2:11][C:12](=[CH2:13])[CH3:14])=[CH:43][CH:44]=1)([O-:3])=[O:2]
Reactant: C=C(C)C(C(=O)OCc1ccc([N+](=O)[O-])cc1)N1C(=O)C(NC(=O)COc2ccccc2)C1SSc1nc2ccccc2s1
Agent: [Ag+]
Agent: Cc1ccc(S(=O)[O-])cc1
Solvent: CC(C)=O
Solvent: O
Product: C=C(C)CC(=O)OCc1ccc([N+](=O)[O-])cc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
(ci) 1.58 g (1.2 equivalents) of silver p-toluenesulphinate are added in portions, in the course of 10 minutes, to a solution of 3.25 g (5.0 mmols) of 2-[4-(benzthiazol-2-yldithio)-3-phenoxyacetamido-2-oxoazetidin-1-yl]-3-methylenebutyric acid p-nitrobenzyl ester in 200 ml of acetone/water, 9:1 (v/v). The suspension is stirred for one hour at room temperature, filtered and further processed as described in Example 1(c). 2-[4-(p]Toluenesulphonylthio)-3-phenoxyacetamido-2-oxoazetidin-1-yl]-3-methylenebutyric acid p-nitrobenzyl ester is obtained in quantitative yield.
Reaction SMILES: N(C(OC(C)C)=O)=NC(OC(C)C)=O.[CH:15]1([C@@:20]([OH:30])([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[C:21]([OH:23])=[O:22])[CH2:19][CH2:18][CH2:17][CH2:16]1.[C:31]([O:35][C:36]([N:38]1[CH2:42][CH2:41][C@@H:40](O)[CH2:39]1)=[O:37])([CH3:34])([CH3:33])[CH3:32].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1COCC1>[C:31]([O:35][C:36]([N:38]1[CH2:42][CH2:41][C@@H:40]([O:22][C:21](=[O:23])[C@:20]([CH:15]2[CH2:19][CH2:18][CH2:17][CH2:16]2)([OH:30])[C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=2)[CH2:39]1)=[O:37])([CH3:34])([CH3:32])[CH3:33]
Reactant: O=C(O)[C@](O)(c1ccccc1)C1CCCC1
Reactant: CC(C)(C)OC(=O)N1CC[C@@H](O)C1
Agent: CC(C)OC(=O)N=NC(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N1CC[C@@H](OC(=O)[C@](O)(c2ccccc2)C2CCCC2)C1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
At room temperature, diisopropyl azodicarboxylate (980 μl, 5 mmol) was slowly added to a mixture of (R)-cyclopentylhydroxyphenylacetic acid (1.1 g, 5 mmol), (R)-3-hydroxypyrrolidine-1-carboxylic acid t-butyl ester (1.0 g, 5.5 mmol), and triphenyl-phosphine (1.3 g, 5 mmol) in 10 ml of THF. The reaction mixture was then stirred at room temperature overnight.
Reaction SMILES: [CH3:1][C:2]1[C:26]([CH3:27])=[CH:25][C:5]2[N:6]([C:19](=[O:24])[CH2:20][N:21]([CH3:23])[CH3:22])[C:7]3[N:18]=[CH:17][CH:16]=[CH:15][C:8]=3[C:9]3[N:10]([C:11](=[O:14])[NH:12][N:13]=3)[C:4]=2[CH:3]=1.[H-].[Na+].[CH3:30][N:31]([CH3:36])[CH2:32][CH2:33][CH2:34]Cl>CN(C)C=O.C1(C)C(C)=CC=CC=1>[CH3:1][C:2]1[C:26]([CH3:27])=[CH:25][C:5]2[N:6]([C:19](=[O:24])[CH2:20][N:21]([CH3:23])[CH3:22])[C:7]3[N:18]=[CH:17][CH:16]=[CH:15][C:8]=3[C:9]3[N:10]([C:11](=[O:14])[N:12]([CH2:34][CH2:33][CH2:32][N:31]([CH3:36])[CH3:30])[N:13]=3)[C:4]=2[CH:3]=1
Reactant: CN(C)CCCCl
Reactant: Cc1cc2c(cc1C)-n1c(n[nH]c1=O)-c1cccnc1N2C(=O)CN(C)C
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: Cc1ccccc1C
Product: Cc1cc2c(cc1C)-n1c(nn(CCCN(C)C)c1=O)-c1cccnc1N2C(=O)CN(C)C
Reaction time: 22 h

Procedure:
In the manner given in Example 25, to 6,7-dimethyl-2,9-dihydro-9-[(dimethylamino)acetyl]-3H-pyrido[3,2-c]-s-triazolo[4,3-a][1,5]benzodiazepin-3-one in dimethylformamide is added a solution of sodium hydride in mineral oil. The mixture is allowed to react to about 95° C. for 40 minutes and after cooling [3-(dimethylamino)-propyl]chloride in xylene is added. The mixture is kept at 95°-100° C. for a period of 22 hours, evaporated and worked up as in example 25 to give 6,7-dimethyl-2,9-dihydro-2-[3-(dimethylamino)propyl]-9-[(dimethylamino)-acetyl]-3H-pyrido[3,2-c]-s-triazolo[4,3-a][1,5]benzodiazepin-3-one.