Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[F:11])[C:5]([OH:7])=O.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH2:45]([O:47][C:48](=[O:60])[C@H:49]([OH:59])[C@H:50]([NH2:58])[CH2:51][C:52]1[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=1)[CH3:46]>C(Cl)Cl>[CH2:45]([O:47][C:48](=[O:60])[C@H:49]([OH:59])[C@H:50]([NH:58][C:5](=[O:7])[C:4]1[CH:8]=[CH:9][C:10]([F:11])=[C:2]([Br:1])[CH:3]=1)[CH2:51][C:52]1[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=1)[CH3:46]
Reactant: O=C(O)c1ccc(F)c(Br)c1
Reactant: CCOC(=O)[C@H](O)[C@H](N)Cc1ccccc1
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: CCOC(=O)[C@H](O)[C@@H](Cc1ccccc1)NC(=O)c1ccc(F)c(Br)c1
Reaction time: 1 h

Procedure:
3-Bromo-4-fluorobenzoic acid (109 mg, 497 μmol, 1.0 eq.), DIPEA (273 μL, 3.2 eq.), HATU (189 mg, 497 μmol, 1.0 eq.), and (2R,3R)-3-amino-2-hydroxy-4-phenyl-butyric acid ethyl ester (129 mg, 497 μmol, 1.0 eq.) were combined in DCM (2 mL) and stirred for 1 hour. The crude reaction was then chromatographed (0-80% EtOAc/hexanes gradient) to yield (2R,3R)-3-(3-bromo-4-fluoro-benzoylamino)-2-hydroxy-4-phenyl-butyric acid ethyl ester.
Reaction SMILES: F[C:2]1[CH:7]=[CH:6][C:5]([S:8]([NH2:11])(=[O:10])=[O:9])=[CH:4][C:3]=1[C:12]([F:15])([F:14])[F:13].[O:16]1[CH2:21][CH2:20][CH:19]([CH2:22][NH2:23])[CH2:18][CH2:17]1.C(N(CC)C(C)C)(C)C>CS(C)=O.C(OCC)(=O)C>[O:16]1[CH2:21][CH2:20][CH:19]([CH2:22][NH:23][C:2]2[CH:7]=[CH:6][C:5]([S:8]([NH2:11])(=[O:10])=[O:9])=[CH:4][C:3]=2[C:12]([F:15])([F:14])[F:13])[CH2:18][CH2:17]1
Reactant: NCC1CCOCC1
Reactant: NS(=O)(=O)c1ccc(F)c(C(F)(F)F)c1
Solvent: CS(C)=O
Solvent: CCOC(C)=O
Solvent: CCN(C(C)C)C(C)C
Product: NS(=O)(=O)c1ccc(NCC2CCOCC2)c(C(F)(F)F)c1
Temperature: 90 °C

Procedure:
A mixture of 4-fluoro-3-(trifluoromethyl)benzenesulfonamide (1.056 g), (tetrahydro-2H-pyran-4-yl)methanamine (0.5 g) and N,N-diisopropylethylamine (1.68 g) in anhydrous dimethylsulfoxide (15 mL) solution was heated at 90° C. overnight. The reaction mixture was cooled to room temperature and diluted with ethyl acetate. The organic phase was washed with water, brine, dried over anhydrous sodium sulfate, filtered and concentrated to afford the title compound.
Reaction SMILES: [Na+].[F:2][C:3]1[C:8]([CH3:9])=[CH:7][C:6]([NH:10][CH2:11][C:12]([O-])=[O:13])=[C:5]([N+:15]([O-])=O)[CH:4]=1.O.O.[Sn](Cl)Cl>C(O)C>[F:2][C:3]1[CH:4]=[C:5]2[C:6]([NH:10][CH2:11][C:12](=[O:13])[NH:15]2)=[CH:7][C:8]=1[CH3:9]
Reactant: Cc1cc(NCC(=O)[O-])c([N+](=O)[O-])cc1F
Agent: Cl[Sn]Cl
Agent: [Na+]
Solvent: O
Solvent: CCO
Product: Cc1cc2c(cc1F)NC(=O)CN2
Temperature: 25 °C
Yield: 32.4 %

Procedure:
A mixture of N-(4-fluoro-5-methyl-2-nitrophenyl)glycine sodium salt (0.125 g, 0.548 mmol) and tin (II) chloride dihydrate (0.370 g, 1.64 mmol, Aldrich, used as received) in ethanol (3.0 mL) was refluxed for 30 min. It was then cooled to room temperature and the solvent was removed under vacuum. The residue was diluted with water (4.0 mL) and basified with saturated NaHCO3 to pH~8. The resulting suspension was extracted with ethyl acetate (30 mL). The extract was dried over Na2SO4 and evaporated to yield 0.032 g of the title compound as a yellow powder, which was used for the next reaction; 1H NMR (DMSO-d6): 2.024 (s, 3H), 3.607 (s, 2H), 5.751 (s, 1H), 6.453 (d, 1H, J=9.9 Hz), 6.456 (d, 1H, J=8.1 Hz), 10.162 (s, 1H).
Reaction SMILES: [CH2:1]([S:3]([C:6]1[CH:7]=[C:8]([C:12]2[CH:20]=[CH:19][C:18]([OH:21])=[C:17]3[C:13]=2[C:14]2[CH:25]=[C:24]([CH3:26])[CH:23]=[N:22][C:15]=2[NH:16]3)[CH:9]=[CH:10][CH:11]=1)(=[O:5])=[O:4])[CH3:2].C(S(C1C=C(C2C=CC(OC[CH2:49][CH2:50][N:51]([CH3:53])[CH3:52])=C3C=2C2C=C(C)C=NC=2N3)C=CC=1)(=O)=O)C>>[CH2:1]([S:3]([C:6]1[CH:7]=[C:8]([C:12]2[CH:20]=[CH:19][C:18]([O:21][CH2:49][CH2:50][N:51]([CH3:53])[CH3:52])=[C:17]3[C:13]=2[C:14]2[CH:25]=[C:24]([CH3:26])[CH:23]=[N:22][C:15]=2[NH:16]3)[CH:9]=[CH:10][CH:11]=1)(=[O:5])=[O:4])[CH3:2]
Reactant: CCS(=O)(=O)c1cccc(-c2ccc(OCCCN(C)C)c3[nH]c4ncc(C)cc4c23)c1
Reactant: CCS(=O)(=O)c1cccc(-c2ccc(O)c3[nH]c4ncc(C)cc4c23)c1
Product: CCS(=O)(=O)c1cccc(-c2ccc(OCCN(C)C)c3[nH]c4ncc(C)cc4c23)c1

Procedure:
The title compound was synthesized from Compound 157 using an analogous procedure to that outlined in the preparation of Compound 205. 1H NMR (400 MHz, MeOD) δ ppm 1.29 (t, J=7.33 Hz, 3H) 2.32 (s, 3H) 2.91 (t, J=5.31 Hz, 2H) 4.34 (t, J=5.43 Hz, 2H) 7.07-7.14 (m, 2H) 7.65 (d, J=2.02 Hz, 1H) 7.82 (t, J=7.83 Hz, 1H) 7.94-7.98 (m, 1H) 8.02 (dd, J=7.33, 1.52 Hz, 1H) 8.15 (t, J=1.64 Hz, 1H) 8.20 (d, J=2.02 Hz, 1H) [M+H] calc'd for C24H27N3O3S, 438; found, 438.
Reaction SMILES: Cl.[CH2:2]([C:6]1[CH:11]=[CH:10][C:9]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([NH:18]N)[CH:13]=2)=[CH:8][CH:7]=1)[CH2:3][CH2:4][CH3:5].C[O:21][C:22]([C:24]1[CH:25]=[C:26]2[C:30](=[CH:31][CH:32]=1)[C:29](=O)[CH2:28][CH2:27]2)=[O:23]>>[CH2:2]([C:6]1[CH:11]=[CH:10][C:9]([C:12]2[CH:17]=[CH:16][C:15]3[C:28]4[CH2:27][C:26]5[C:30](=[CH:31][CH:32]=[C:24]([C:22]([OH:23])=[O:21])[CH:25]=5)[C:29]=4[NH:18][C:14]=3[CH:13]=2)=[CH:8][CH:7]=1)[CH2:3][CH2:4][CH3:5]
Reactant: COC(=O)c1ccc2c(c1)CCC2=O
Reactant: CCCCc1ccc(-c2cccc(NN)c2)cc1
Agent: Cl
Product: CCCCc1ccc(-c2ccc3c4c([nH]c3c2)-c2ccc(C(=O)O)cc2C4)cc1

Procedure:
By reacting (4′-Butyl-biphenyl-3-yl)-hydrazine hydrochloride (example 70, step 1) and 1-oxo-indan-5-carboxylic acid methyl ester as described in example 1 followed by hydrolysis as described in example 2 the title material is obtained in similar yield. ESMS m/z 382.1 (M+H+).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([S:8]([CH3:11])(=[O:10])=[O:9])[CH:5]=[C:4]([Cl:12])[C:3]=1[N:13]1[CH:22]=[C:16]2[CH:17]=[N+:18]([O-])[CH:19]=[CH:20][C:15]2=[N:14]1.P(Cl)(Cl)([Cl:25])=O>[Cl-].C([N+](CCCC)(CCCC)CCCC)CCC>[Cl:25][C:17]1[C:16]2=[CH:22][N:13]([C:3]3[C:2]([Cl:1])=[CH:7][C:6]([S:8]([CH3:11])(=[O:10])=[O:9])=[CH:5][C:4]=3[Cl:12])[N:14]=[C:15]2[CH:20]=[CH:19][N:18]=1
Reactant: O=P(Cl)(Cl)Cl
Reactant: CS(=O)(=O)c1cc(Cl)c(-n2cc3c[n+]([O-])ccc3n2)c(Cl)c1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [Cl-]
Product: CS(=O)(=O)c1cc(Cl)c(-n2cc3c(Cl)nccc3n2)c(Cl)c1
Temperature: 85 °C
Yield: 35 %

Procedure:
2-(2,6-Dichloro-4-methanesulfonylphenyl)-2H-pyrazolo[4,3-c]pyridine-5-oxide (640 mg, 1.79 mmol) was added to a solution of tetrabutylammonium chloride (497 mg, 1.79 mmol) in phosphorous oxychloride (5 mL) and the reaction mixture was heated at 85° C. for 4 hours. The reaction mixture was cooled and partitioned between ethyl acetate and sodium hydrogen carbonate (sat. aq.). The organic phase was washed with sodium hydrogen carbonate (sat. aq.) and brine, dried over anhydrous sodium sulfate, and concentrated to dryness under reduced pressure. The residue was purified by silica gel flash chromatography (40% ethyl acetate in cyclohexane) to afford the title compound as a white solid (238 mg, 35% yield). 1H NMR (300 MHz, DMSO-d6): δ 9.35 (d, J=1.0 Hz, 1H), 8.36 (s, 2H), 8.14 (d, J=6.3 Hz, 1H), 7.76 (dd, J=6.3, 1.0 Hz, 1H), 3.49 (s, 3H). LCMS (Method D): RT=3.19 min, m/z: 376 [M+H+].
Reaction SMILES: [F:1][C:2]([F:32])([F:31])[CH2:3][O:4][C:5]1[CH:6]=[C:7]([C:15]2[CH:20]=[C:19]([C:21]([F:24])([F:23])[F:22])[N:18]3[N:25]=[CH:26][C:27]([C:28](O)=O)=[C:17]3[N:16]=2)[CH:8]=[CH:9][C:10]=1[C:11]([F:14])([F:13])[F:12].[NH2:33][C:34]1[CH:43]=[CH:42][C:37]([C:38]([NH:40][OH:41])=[NH:39])=[CH:36][N:35]=1>>[F:32][C:2]([F:1])([F:31])[CH2:3][O:4][C:5]1[CH:6]=[C:7]([C:15]2[CH:20]=[C:19]([C:21]([F:22])([F:23])[F:24])[N:18]3[N:25]=[CH:26][C:27]([C:28]4[O:41][N:40]=[C:38]([C:37]5[CH:42]=[CH:43][C:34]([NH2:33])=[N:35][CH:36]=5)[N:39]=4)=[C:17]3[N:16]=2)[CH:8]=[CH:9][C:10]=1[C:11]([F:12])([F:13])[F:14]
Reactant: N=C(NO)c1ccc(N)nc1
Reactant: O=C(O)c1cnn2c(C(F)(F)F)cc(-c3ccc(C(F)(F)F)c(OCC(F)(F)F)c3)nc12
Product: Nc1ccc(-c2noc(-c3cnn4c(C(F)(F)F)cc(-c5ccc(C(F)(F)F)c(OCC(F)(F)F)c5)nc34)n2)cn1

Procedure:
The title compound was prepared from 5-[3-(2,2,2-trifluoro-ethoxy)-4-trifluoromethyl-phenyl]-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidine-3-carboxylic acid (example C.10) (237 mg, 0.5 mmol) and 6-amino-N-hydroxy-nicotinamidine (example B.4) (114 mg, 0.75 mmol) according to general procedure II. Obtained after flash chromatography on silica gel (ethyl acetate/heptane) and further purification by crystallization (dichloromethane/hexane) as a yellow solid (129 mg, 44%). MS (ISP) 590.3 [(M+H)+]; mp 284° C.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][N:12]([CH2:15][CH2:16][C:17]2[S:21][C:20]([C:22](O)=[O:23])=[CH:19][CH:18]=2)[C:11](=[O:25])[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1N=CN(C(N2C=NC=C2)=O)C=1.[BH4-].[Na+].C([O-])([O-])=O.[Na+].[Na+]>C1COCC1.O.[K].S([O-])(O)(=O)=O>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][N:12]([CH2:15][CH2:16][C:17]2[S:21][C:20]([CH2:22][OH:23])=[CH:19][CH:18]=2)[C:11](=[O:25])[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C(O)c1ccc(CCn2ccc(OCc3ccccc3)cc2=O)s1
Agent: O=C([O-])[O-]
Agent: O=C(n1ccnc1)n1ccnc1
Agent: O=S(=O)([O-])O
Solvent: C1CCOC1
Solvent: O
Product: O=c1cc(OCc2ccccc2)ccn1CCc1ccc(CO)s1
Temperature: 50 °C
Reaction time: 0.5 h

Procedure:
To 530 mg (1.49 mmol) 5-[2-(4-benzyloxy-2-oxo-2H-pyridin-1-yl)-ethyl]-thiophene-2-carboxylic acid (preparation 11c) in 15 mL THF is added at RT 266 mg (1.64 mmol) CDI. The reaction mixture is stirred 30 min at 50° C. and is then poured into a solution of 169 mg (4.47 mmol) sodium borohydride in 40 mL water. The mixture is stirred 1 h at RT, diluted with saturated aqueous potassium-hydrogen-sulfate-solution and stirred for another 20 min. The mixture is neutralized with saturated aqueous Na2CO3-solution. The aqueous phase is extracted three times with EtOAc/MeOH. The combined organic phase is dried over MgSO4, filtered and the solvent is evaporated to afford the product.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:13])[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][OH:12].CCN(CC)CC.[C:21]([Si:25](Cl)([C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)([CH3:24])([CH3:23])[CH3:22].[NH4+].[Cl-]>C(Cl)Cl.CN(C1C=CN=CC=1)C>[CH3:1][O:2][C:3](=[O:13])[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][O:12][Si:25]([C:21]([CH3:24])([CH3:23])[CH3:22])([C:32]1[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=1)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1
Reactant: CC(C)(C)[Si](Cl)(c1ccccc1)c1ccccc1
Reactant: COC(=O)CCCCCCCCO
Agent: CN(C)c1ccncc1
Agent: [Cl-]
Agent: [NH4+]
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COC(=O)CCCCCCCCO[Si](c1ccccc1)(c1ccccc1)C(C)(C)C
Temperature: 25 °C
Reaction time: 12 h

Procedure:
A solution of methyl-9-hydroxy-nonanoate (0.838 g, 4.46 mmol, 1.0 equiv: Aldrich) in CH2Cl2 (15 mL, 0.3 M) was treated successively with Et3N (0.75 mL, 5.38 mmol, 1.2 equiv), t-butylchlorodiphenylsilane (1.28 mL, 4.93 mmol, 1.1 equiv), and DMAP (0.180 g, 1.48 mmol, 0.33 equiv), and the reaction mixture was stirred at 25° C. for 12 h. Saturated aqueous NH4Cl was added to the reaction mixture and the mixture was partitioned between CH2Cl2 (100 mL) and H2O (100 mL). The organic layer was dried (Na2SO4) and concentrated under reduced pressure. Chromatography (SiO2, 5 cm×15 cm, 0-5% EtOAc-hexanes gradient elution) afforded the intermeidate as a clear, colorless oil (1.22 g, 1.831 theoretical, 64.1%): 1H NMR (CDCl3, 250 MHz) δ 7.66 (m, 4H, ArH), 7.38 (m, 6H, ArH), 3.67-3.62 (m, 5H, C(O)OCH3 and CH2OTBDPS), 2.30 (t, 2H, J=7.4 Hz, CH2C(O)OCH3), 1.58 (m, 4H, CH2CH2OTBDPS and CH2CH2C(O)OCH3), 1.28 (b s, 8H, alkyl protons), 1.05 (s, 9H, C(CH3)3).
Reaction SMILES: [F:1][C:2]([F:20])([F:19])[O:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[O:14][N:13]=[C:12]([C:15]([NH:17][NH2:18])=O)[CH:11]=2)=[CH:6][CH:5]=1.Cl.[C:22](=N)([NH2:24])[CH3:23].[OH-].[Na+]>C1COCC1>[CH3:23][C:22]1[N:24]=[C:15]([C:12]2[CH:11]=[C:10]([C:7]3[CH:8]=[CH:9][C:4]([O:3][C:2]([F:20])([F:19])[F:1])=[CH:5][CH:6]=3)[O:14][N:13]=2)[NH:17][N:18]=1
Reactant: CC(=N)N
Reactant: NNC(=O)c1cc(-c2ccc(OC(F)(F)F)cc2)on1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Product: Cc1n[nH]c(-c2cc(-c3ccc(OC(F)(F)F)cc3)on2)n1
Temperature: 25 °C
Yield: 44.2 %

Procedure:
To a solution of 5-(4-(trifluoromethoxy)phenyl)isoxazole-3-carbohydrazide (4.4 g, 15.3 mmol) and acetimidamide hydrochloride (2.2 g, 23.0 mmol) in dry THF (100 mL) was added NaOH (920 mg, 23.0 mmol), and the resulting mixture was refluxed for 16 h. The solution was then cooled to RT and concentrated under reduced pressure, the residue was partitioned between H2O (80 mL) and EtOAc (2×100 mL). The organic layer was dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography (Petroleum ether:EtOAc=1:2) to afford the title compound as a yellow solid (2.1 g, 44.3%). MS (ES+) C13H9F3N4O2 requires: 310. found: 311 [M+H]+.
Reaction SMILES: [CH2:1]([N:3]1[C:7]([N:8]2[CH2:12][CH2:11][CH2:10][CH2:9]2)=[N:6][C:5]([C:13]#[C:14][C:15]2[N:25]=[C:18]3[C:19]([CH3:24])=[N:20][CH:21]=[C:22]([CH3:23])[N:17]3[N:16]=2)=[N:4]1)[CH3:2]>[Pd].CO>[CH2:1]([N:3]1[C:7]([N:8]2[CH2:9][CH2:10][CH2:11][CH2:12]2)=[N:6][C:5]([CH2:13][CH2:14][C:15]2[N:25]=[C:18]3[C:19]([CH3:24])=[N:20][CH:21]=[C:22]([CH3:23])[N:17]3[N:16]=2)=[N:4]1)[CH3:2]
Reactant: CCn1nc(C#Cc2nc3c(C)ncc(C)n3n2)nc1N1CCCC1
Agent: [Pd]
Solvent: CO
Product: CCn1nc(CCc2nc3c(C)ncc(C)n3n2)nc1N1CCCC1
Temperature: 25 °C
Reaction time: 20 h
Yield: 96.4 %

Procedure:
A mixture of 2-((1-ethyl-5-(pyrrolidin-1-yl)-1H-1,2,4-triazol-3-yl)ethynyl)-5,8-dimethyl-[1,2,4]triazolo[1,5-a]pyrazine (43 mg, 128 μmol, Eq: 1.00) and palladium on carbon 10% (13.6 mg, 12.8 μmol, Eq: 0.1) in methanol (10 ml) was stirred for 20 hours at 25° C. under hydrogen atmosphere. The catalyst was filtered off, the filtrate was evaporated affording 2-(2-(1-ethyl-5-(pyrrolidin-1-yl)-1H-1,2,4-triazol-3-yl)ethyl)-5,8-dimethyl-[1,2,4]triazolo[1,5-a]pyrazine (42 mg, 96.5%) as an light yellow oil. MS: m/z=341.5 (M+H+)
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[C:7]([O:9][CH3:10])[N:6]=[C:5]([CH:11]2[C:19]3[C:14](=[N:15][CH:16]=[CH:17][CH:18]=3)[C:13](=[O:20])[O:12]2)[N:4]=1.CO.[O-][Cl:24].[Na+]>ClCCl>[Cl:24][C:11]1([C:5]2[N:4]=[C:3]([O:2][CH3:1])[CH:8]=[C:7]([O:9][CH3:10])[N:6]=2)[C:19]2[C:14](=[N:15][CH:16]=[CH:17][CH:18]=2)[C:13](=[O:20])[O:12]1
Reactant: [O-]Cl
Reactant: COc1cc(OC)nc(C2OC(=O)c3ncccc32)n1
Agent: [Na+]
Solvent: CO
Solvent: ClCCl
Product: COc1cc(OC)nc(C2(Cl)OC(=O)c3ncccc32)n1

Procedure:
A mixture of 490 mg of 5-(4,6-dimethoxy-2-pyrimidinyl)furo[3,4,b]pyridine-7(5H)one and 50 ml of methanol is heated at 55° for 1/2 hour or until a homogeneous solution is formed. 2.6 g of NaOCl (common house bleach) is added dropwise. The mixture is taken up in dichloromethane an the organic phase separated and evaporated to dryness to yield the title compound, mp 146°-148° C.
Reaction SMILES: COC(OC)[CH2:4][N:5]([CH3:10])[C:6](=[O:9])[CH2:7][Cl:8].[CH3:13][CH:14]([OH:18])[CH:15]([OH:17])[CH3:16].C1(C)C=CC(S(O)(=O)=O)=CC=1>CO>[CH3:16][CH:15]1[CH:14]([CH3:13])[O:18][CH:4]([N:5]([CH3:10])[C:6](=[O:9])[CH2:7][Cl:8])[O:17]1
Reactant: COC(CN(C)C(=O)CCl)OC
Reactant: CC(O)C(C)O
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: CO
Product: CC1OC(N(C)C(=O)CCl)OC1C
Temperature: 110 °C

Procedure:
N-(2,2-Dimethoxyethyl)-N-methyl-2-chloroacetamide (97.8 grams; 0.5 mole), 2,3-butanediol (45 grams) and 0.2 grams p-toluenesulfonic acid were charged into a glass reaction vessel fitted with a mechanical stirrer, thermometer, distilling head and condenser. The reaction mixture was heated at about 90° C. to 100° for a period of 5 hours. Little reaction occurred as shown by the absence of methanol distilled. The reaction mixture was then heated at about 110° C., for about 2 hours at atmospheric pressure, then 1 hour at reduced pressure. Under these more rigorous conditions, methanol was formed and was distilled off. At the conclusion of the reaction, the reaction mixture was distilled and the fraction boiling at 127° C. to 130° C. at 0.55 mm Hg was the desired product N-(4,5-dimethyl-1,3-dioxolan-2-yl)-N-methyl-2-chloroacetamide.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6]([C:8](OC)=[O:9])[CH:5]=[C:4]([N:12]2[CH2:16][C@H:15]([OH:17])[C@@H:14]([OH:18])[CH2:13]2)[N:3]=1.[NH3:19]>CO>[Cl:1][C:2]1[N:7]=[C:6]([C:8]([NH2:19])=[O:9])[CH:5]=[C:4]([N:12]2[CH2:16][C@H:15]([OH:17])[C@@H:14]([OH:18])[CH2:13]2)[N:3]=1
Reactant: N
Reactant: COC(=O)c1cc(N2C[C@H](O)[C@@H](O)C2)nc(Cl)n1
Solvent: CO
Product: NC(=O)c1cc(N2C[C@H](O)[C@@H](O)C2)nc(Cl)n1
Temperature: 25 °C
Reaction time: 8 h
Yield: 91 %

Procedure:
A solution of methyl 2-chloro-6-((3S,4S)-3,4-dihydroxypyrrolidin-1-yl)pyrimidine-4-carboxylate (1.132 g, 4.14 mmol) in 7M ammonia in MeOH (12 mL) was allowed to sit at ambient temperature overnight. The reaction mixture was evaporated in vacuo and the residue was taken up in EtOAc (10 mL). The residue first dissolved then quickly precipitated a solid. After cooling back down to ambient temperature the precipitated solid was filtered off then dried under vacuum at 40° C. to give 2-chloro-6-((3S,4S)-3,4-dihydroxypyrrolidin-1-yl)pyrimidine-4-carboxamide as a tan powder (0.969 g, 3.75 mmol, 91% yield). LC/MS: m/z=259.2 [M+H]+.
Reaction SMILES: [N:1]#N.N#N.N.N.[C:7](=[O:10])([O-:9])[NH2:8].[NH4+]>N>[C:7](=[O:9])([O-:10])[NH2:8].[NH4+:1].[C:7](=[O:10])=[O:9].[NH3:8]
Reactant: N#N
Agent: N
Agent: NC(=O)[O-]
Agent: [NH4+]
Product: O=C=O

Procedure:
SCR catalytic converter 12 situated in exhaust-gas region 11 of internal combustion engine 10 reduces the nitrogen oxides NO and NO2 contained in the exhaust gas of internal combustion engine 10 to nitrogen N2 SCR catalytic converter 12 requires ammonia NH3 for the reduction. The ammonia is prepared in ammonia source 19, which performs a thermal decomposition of ammonium carbamate for example. In the thermolysis of ammonium carbamate in a thermolysis reactor, CO2 is produced in addition to NH3. Only NH3 will be used in the following to designate the product gas stream of ammonia source 19. Another implementation option of ammonia source 19 provides for the ammonia to be desorbed from a storage material (e.g. a metal chloride) while the storage material is being heated. In addition it is possible that ammonia source 19 takes the form of an ammonia synthesis device.
Reaction SMILES: [Mg].[Cl-].[Ce+3].[Cl-].[Cl-].Br[CH2:7][CH2:8][CH2:9][CH2:10]Br.CO[C:14](=[O:32])[C:15]1[CH:20]=[CH:19][C:18]([C:21]2[NH:22][C:23](=[O:31])[C:24]3[N:25]([CH:27]=[C:28]([F:30])[CH:29]=3)[CH:26]=2)=[CH:17][CH:16]=1.C[Mg]Cl>C1COCC1>[F:30][C:28]1[CH:29]=[C:24]2[C:23](=[O:31])[NH:22][C:21]([C:18]3[CH:17]=[CH:16][C:15]([C:14]4([OH:32])[CH2:10][CH2:9][CH2:8][CH2:7]4)=[CH:20][CH:19]=3)=[CH:26][N:25]2[CH:27]=1
Reactant: BrCCCCBr
Reactant: COC(=O)c1ccc(-c2cn3cc(F)cc3c(=O)[nH]2)cc1
Agent: C[Mg]Cl
Agent: [Ce+3]
Agent: [Cl-]
Solvent: C1CCOC1
Product: O=c1[nH]c(-c2ccc(C3(O)CCCC3)cc2)cn2cc(F)cc12
Temperature: 0 °C

Procedure:
A 25 ml round-bottom flask is flushed with nitrogen and charged with 6.9 ml dry THF, 134 mg (5.50 mmol) magnesium turnings and 49 mg (0.20 mmol) cerium(III) chloride. Under stirring, the suspension is cooled to 0° C. Then 378 μl (3.20 mmol) 1,4-dibromobutane is added, the suspension is allowed to reach room temperature, stirred for 30 minutes at this temperature and again cooled to 0° C. Then, a solution of 286 mg (1.00 mmol) 4-(7-fluoro-1-oxo-1,2-dihydro-pyrrolo[1,2-a]pyrazin-3-yl)-benzoic acid methyl ester in 2.3 ml THF is added dropwise. The reaction mixture is stirred for 30 minutes at 0° C. and for 1 hour at room temperature. The reaction mixture is quenched with saturated ammonium chloride solution. To a suspension of 5.73 g (20.0 mmol) 4-(7-fluoro-1-oxo-1,2-dihydro-pyrrolo[1,2-a]pyrazin-3-yl)-benzoic acid methyl ester in 85 ml THF are added 5.42 g (22.0 mmol) and the mixture is stirred for 1 h at ambient temperature under nitrogen. Then 30.5 ml (84.0 mmol) of a 20% solution of methylmagnesium chloride in THF is added dropwise and the reaction mixture is stirred for 30 minutes at room temperature. The reaction mixture is partitioned between ethyl acetate and water. The organic phase is dried over sodium sulfate and evaporated. The residue is chromatographed on a silica gel column with cyclohexane/ethyl acetate as eluent to afford 7-fluoro-3-[4-(1-hydroxy-cyclopentyl)-phenyl]-2H-pyrrolo[1,2-a]pyrazin-1-one as light orange powder; HPLC/MS 2.37 (B), [M+H] 313; 1H NMR (400 MHz, DMSO-d6) δ [ppm] 10.99 (s, 1H), 7.62 (s, 1H), 7.59 (d, J=8.5 Hz, 2H), 7.54 (d, J=8.5 Hz, 2H), 7.48 (dd, J=3.4, 1.9 Hz, 1H), 6.75 (d, J=1.8 Hz, 1H), 4.85 (s, 1H), 1.92-1.80 (m, 6H), 1.80-1.69 (m, 2H).
Reaction SMILES: [NH2:1][CH2:2][C@H:3]([NH:9][C:10]([CH2:12][NH:13][C:14]([C:16]1[CH:21]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:19]=[CH:18][C:17]=1[NH:26][C:27]([N:29]1[CH2:32][CH2:31][CH2:30]1)=[O:28])=[O:15])=[O:11])[C@@H:4]([OH:8])[CH2:5][CH2:6][CH3:7].[CH3:33][C:34]([CH3:38])([CH3:37])[CH:35]=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClC(Cl)C>[CH3:33][C:34]([CH3:38])([CH3:37])[CH2:35][NH:1][CH2:2][C@H:3]([NH:9][C:10]([CH2:12][NH:13][C:14]([C:16]1[CH:21]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:19]=[CH:18][C:17]=1[NH:26][C:27]([N:29]1[CH2:32][CH2:31][CH2:30]1)=[O:28])=[O:15])=[O:11])[C@@H:4]([OH:8])[CH2:5][CH2:6][CH3:7]
Reactant: CCC[C@H](O)[C@H](CN)NC(=O)CNC(=O)c1cc(C(F)(F)F)ccc1NC(=O)N1CCC1
Reactant: CC(C)(C)C=O
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: CC(Cl)Cl
Product: CCC[C@H](O)[C@H](CNCC(C)(C)C)NC(=O)CNC(=O)c1cc(C(F)(F)F)ccc1NC(=O)N1CCC1
Temperature: 25 °C
Reaction time: 3 h
Yield: 51.9 %

Procedure:
Azetidine-1-carboxylic acid (1S,2S)-(2-{[(1-aminomethyl-2-hydroxy-pentylcarbamoyl)-methyl]-carbamoyl}-4-trifluoromethyl-phenyl)-amide (165 mg, 0.35 mmol, see procedure 1b) was dissolved in dichloroethane (4 mL). The resultant solution was charged sequentially with trimethylacetaldehyde (20.5 mg, 0.2 mmol) and sodium triacetoxyborohydride (148 mg, 0.7 mmol), stirred for 3 h at RT, quenched with sat. NaHCO3, and extracted twice with EtOAc. The organic extracts were combined, washed with brine, dried (Na2SO4), filtered, and concentrated in vacuo. The residue was purified by reverse-phase HPLC to afford the title compound (55 mg) as a white powder after lypholization. MS found: (M+H)+=530.5.
Reaction SMILES: Cl([O-])(=O)(=O)=O.Cl[C:7]1[CH2:12][C:11]([CH3:14])([CH3:13])[CH2:10][C:9](=[N+:15]2[CH2:19][CH2:18][CH2:17][CH2:16]2)[CH:8]=1.[CH2:20]([N:22]1[C:29](=[O:30])[CH2:28][C:26](=[O:27])[N:25]([CH2:31][CH3:32])[C:23]1=[S:24])[CH3:21].C(N(CC)CC)C>C(O)C>[CH2:31]([N:25]1[C:26](=[O:27])[C:28](=[C:7]2[CH2:12][C:11]([CH3:14])([CH3:13])[CH2:10][C:9]([N:15]3[CH2:19][CH2:18][CH2:17][CH2:16]3)=[CH:8]2)[C:29](=[O:30])[N:22]([CH2:20][CH3:21])[C:23]1=[S:24])[CH3:32]
Reactant: CC1(C)CC(Cl)=CC(=[N+]2CCCC2)C1
Reactant: CCN1C(=O)CC(=O)N(CC)C1=S
Agent: [O-][Cl+3]([O-])([O-])[O-]
Solvent: CCO
Solvent: CCN(CC)CC
Product: CCN1C(=O)C(=C2C=C(N3CCCC3)CC(C)(C)C2)C(=O)N(CC)C1=S

Procedure:
N-(3-Chloro-5,5-dimethylcyclohex-2-en-1-ylidene)-pyrrolidinium perchlorate (3.1 g., 0.01 mol.), 1,3-diethyl-2-thiobarbituric acid (2.0 g., 0.091 mol.) and triethylamine (3.1 ml.) are dissolved in ethanol (15 ml.) and heated at reflux for 10 minutes. After chilling, the crude dye is collected on a filter, rinsed with ethanol and dried. After one recrystallization from methanol, the yield of purified dye is 2.3 g. (64%), m.p. 226°-227°C. This dye is an excellent spectral sensitizer for photographic silver halide emulsions as shown in Table 2 hereinafter.
Reaction SMILES: [C:1](Cl)(=[O:3])[CH3:2].[CH:5]1([CH:8]([C:14]2[CH:19]=[CH:18][C:17]([O:20][CH2:21][CH3:22])=[CH:16][CH:15]=2)[CH:9]=[C:10]([F:13])[CH2:11][OH:12])[CH2:7][CH2:6]1.C1C=CC=CC=1>N1C=CC=CC=1>[C:1]([O:12][CH2:11][C:10]([F:13])=[CH:9][CH:8]([CH:5]1[CH2:6][CH2:7]1)[C:14]1[CH:19]=[CH:18][C:17]([O:20][CH2:21][CH3:22])=[CH:16][CH:15]=1)(=[O:3])[CH3:2]
Reactant: CCOc1ccc(C(C=C(F)CO)C2CC2)cc1
Reactant: CC(=O)Cl
Solvent: c1ccncc1
Solvent: c1ccccc1
Product: CCOc1ccc(C(C=C(F)COC(C)=O)C2CC2)cc1
Yield: 99 %

Procedure:
The method of Example 11 was repeated using acetyl chloride (1.2 ml), 4-cyclopropyl-4-(4-ethoxyphenyl)-2-fluorobut-2-enol (Example 7) (0.65 g), benzene (34 ml) and pyridine (0.24 ml) to yield the title compound (0.75 g, 99%).