Citric Acid → HCID 69591363, compound

HRID 2269530Notes

Reaction equation

HRID 2269530 reaction equation
CN1CCOCC1.Cl[C:9]1[N:14]=[C:13](OC)[N:12]=[C:11](OC)[N:10]=1.[C:19]([O:23][C:24]([NH:26][C:27]([CH3:42])([CH3:41])[C:28]([NH:30][CH:31]([C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)[C:32]([OH:34])=O)=[O:29])=[O:25])([CH3:22])([CH3:21])[CH3:20].Cl.Cl.NC1N=C([CH:51]([C:61]2[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=2)[C:52]([N:54]2[CH2:59][CH2:58][CH:57]([CH3:60])[CH2:56][CH2:55]2)=[O:53])NC=1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CCOC(C)=O.C1COCC1.C(Cl)Cl>[C:19]([O:23][C:24]([NH:26][C:27]([CH3:41])([CH3:42])[C:28]([NH:30][C@@H:31]([C:32](=[O:34])[NH:10][C:9]1[N:14]=[CH:13][N:12]([CH:51]([C:61]2[CH:62]=[CH:63][CH:64]=[CH:65][CH:66]=2)[C:52]([N:54]2[CH2:55][CH2:56][CH:57]([CH3:60])[CH2:58][CH2:59]2)=[O:53])[CH:11]=1)[C:35]1[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=1)=[O:29])=[O:25])([CH3:20])([CH3:22])[CH3:21]

Participants

9

Reactant 5

HCID 311Citric AcidHCID 79724-MethylmorpholineHCID 184502-Chloro-4,6-dimethoxy-1,3,5-triazineHCID 22252879HCID 22252879, compoundHCID 178428632HCID 178428632, compound

Product 1

HCID 69591363HCID 69591363, compoundYield 48%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

N-methylmorpholine (0.16 mL, 1.49 mmol) was added to a suspension of 2-chloro-4,6-dimethoxy-1,3,5-triazine (268 mg, 1.53 mmol), 2-{2-[(tert-butoxy)carbonylamino]-2-methylpropanoylamino}-2-phenylacetic acid (502 mg, 1.49 mmol), CH2Cl2 (7 mL) and THF (2 mL) at 23° C. The heterogeneous reaction stirred for two hours and 2-(4-aminoimidazolyl)-1-(4-methylpiperidyl)-2-phenylethan-1-one dihydrochloride (613 mg, 1.65 mmol) was added. The mixture was stirred for 15.5 h, and EtOAc (40 mL) and 10% (w/w) aqueous citric acid (18 mL) were added. The layers were separated, and the organic layer was extracted with 15 mL each of saturated NaHCO3 and saturated NaCl. The organic layer was dried (MgSO4), concentrated in vacuo to 590 mg of solid, and purified by flash chromatography (10% i-PA/CHCl3) to yield 440 mg (48%) of a foamy solid: 1H NMR (CDCl3, 300 MHz) d 10.34 (m, 1H), 7.67 (s, 1H), 7.40-7.19 (m, 12H), 6.10 (m, 1H), 5.73 (m, 1H), 4.57 (m, 1H), 3.84 (m, 1H), 3.60 (m, 1H), 2.95 (m, 1H), 2.74-2.58 (m, 1H), 1.65-0.79 (m, 23H); 13C NMR (CDCl3, 75 MHz) 174.0, 167.0, 165.3, 137.7, 136.7, 134.2, 133.5, 133.4, 129.4, 129.3, 129.2, 129.2, 128.7, 128.5, 128.5, 128.3, 128.2, 128.0, 127.2, 127.2, 108.1, 62.1, 62.0, 62.0, 61.9, 57.1, 56.6, 46.0, 46.0, 45.8, 429, 34.2, 33.6, 33.5, 30.8, 30.7, 28.2, 21.5, 21.4 ppm; IR (CDCl3) 1456, 1487, 1560, 1661, 1707, 3010 cm−1; MS (electrospray) m/z 617 (M+H), 438 & 615 (M−H), 436.

Workup

  1. customThe heterogeneous reaction
  2. stirringThe mixture was stirred for 15.5 h
  3. customThe layers were separated
  4. extractionthe organic layer was extracted with 15 mL each of saturated NaHCO3 and saturated NaCl
  5. dry with materialThe organic layer was dried (MgSO4)
  6. concentrationconcentrated in vacuo to 590 mg of solid
  7. custompurified by flash chromatography (10% i-PA/CHCl3)

Sources & evidence

ORD record
ord-8b36d0f8b9634671aaa57a9154dd7c64
Source dataset
uspto-grants-2001_12
Patent number
US06329342B1

Reaction notes

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