Acetic Acid → HCID 178462558, compound

HRID 874448Notes

Reaction equation

HRID 874448 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][N:5]([CH3:27])[C:6]2[C:7]=1[CH:8]=[CH:9][C:10]1[N:19]([C:20]3[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=3)[CH2:18][CH:17]=[C:12]3[NH:13][C:14](=[O:16])[C:15]=2[C:11]=13.C(O)(=O)C.C([BH3-])#N.[Na+].[CH2:36]([N:38]1[CH:42]=[CH:41][C:40]([CH:43]=O)=[N:39]1)[CH3:37]>>[CH2:36]([N:38]1[CH:42]=[CH:41][C:40]([CH2:43][NH:1][C:2]2[CH:3]=[CH:4][N:5]([CH3:27])[C:6]3[C:7]=2[CH:8]=[CH:9][C:10]2[N:19]([C:20]4[CH:21]=[CH:22][C:23]([F:26])=[CH:24][CH:25]=4)[CH2:18][CH:17]=[C:12]4[NH:13][C:14](=[O:16])[C:15]=3[C:11]=24)=[N:39]1)[CH3:37]

Participants

5

Reactant 4

HCID 176Acetic AcidHCID 5003444Sodium cyanoborohydrideHCID 70194151-ethyl-1H-pyrazole-3-carbaldehydeHCID 178480427HCID 178480427, compound

Product 1

HCID 178462558HCID 178462558, compoundYield 41.2%

Procedure

A stock solution of Example 23e (0.164 M in N,N-dimethylacetamide, 255 mL, 0.042 mmol), acetic acid (4 M in methanol, 200 mL, 0.84 mmol), sodium cyanoborohydride (0.31 M in methanol, 200 mL, 0.063 mmol) and 1-ethyl-1H-pyrazole-3-carbaldehyde (0.40 M in N,N-dimethylacetamide, 156 mL, 0.063 mmol) were aspirated from their respective source vials, mixed through a perfluoroalkoxy mixing tube (0.2 mm inner diameter), and loaded into an injection loop. The reaction segment was injected into the flow reactor (Hastelloy coil, 0.75 mm inner diameter, 1.8 mL internal volume) set at 50° C., and passed through the reactor at 180 μL, min−1 (10 minute residence time). Upon exiting the reactor, the reaction mixture was loaded directly into an injection loop and purified by reverse phase HPLC(C8, acetonitrile/water (0.1% ammonium acetate), 5-100%) to give 0.0081 g (41%) of the title compound. 1H NMR (400 MHz, DMSO-d6/D2O) δ 7.57 (m, 2H), 7.07 (d, J=2.75 Hz, 1H), 6.95 (m, 2H), 6.74 (m, 2H), 6.60 (dd, J=8.54, 2.75 Hz, 1H), 6.46 (m, 2H), 6.22 (d, J=2.14 Hz, 1H), 4.28 (s, 2H), 4.10 (q, J=7.12 Hz, 2H), 4.04 (s, 3H), 2.88 (d, J=53.41 Hz, 2H), 1.38 (m, 3H). MS (APCI+) m/z 469.1 (M+H)+.

Workup

  1. additionmixed through a perfluoroalkoxy mixing tube (0.2 mm inner diameter)
  2. customset at 50° C.
  3. custompassed through the reactor at 180 μL, min−1 (10 minute residence time)
  4. custompurified by reverse phase HPLC(C8, acetonitrile/water (0.1% ammonium acetate), 5-100%)

Sources & evidence

ORD record
ord-6fbe66d877d84909aae3d1ab89f3a7bb
Source dataset
uspto-grants-2015_03
Patent number
US08980879B2

Reaction notes

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