Acetic Acid → HCID 178484278, compound

HRID 526747Notes

Reaction equation

HRID 526747 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:12]([CH2:13][N:14]([CH3:18])[CH2:15][CH:16]=O)=[CH:11][NH:10][N:9]=2)=[CH:4][CH:3]=1.[ClH:19].[CH3:20][NH2:21].C(O)(=O)C.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClCCCl.CC#N.O>[ClH:19].[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:12]([CH2:13][N:14]([CH3:18])[CH2:15][CH2:16][NH:21][CH3:20])=[CH:11][NH:10][N:9]=2)=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 5049666Sodium triacetoxyborohydrideHCID 6364545Methylamine hydrochlorideHCID 178484511HCID 178484511, compound

Product 1

HCID 178484278HCID 178484278, compoundYield 47%

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 962WaterSolventHCID 6342AcetonitrileSolvent2×

Procedure

To a stirred solution of 2-([[3-(4-fluorophenyl)-1H-pyrazol-4-yl]methyl](methyl)amino)acetaldehyde (200 mg, 0.81 mmol, 1.00 equiv), methylamine hydrochloride (1 g, 14.81 mmol, 18.31 equiv) and acetic acid (126 mg, 2.10 mmol, 2.59 equiv) in 1,2-dichloroethane (20 mL) was added NaBH(OAc)3 (670 mg). The resulting solution was stirred at room temperature overnight and then quenched by the addition of 10 mL of water. The pH value of the solution was adjusted to 7 with saturated sodium carbonate solution. The resulting mixture was extracted with 2×50 mL of dichloromethane. The combined organic layers was dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was initially purified on a silica gel column eluted with 10% MeOH in CH2Cl2 and the partially purified product was repurified by Prep-HPLC with the following conditions (1#-Pre-HPLC-005(Waters)): Column, XBridge Shield RP18 OBD Column, 5 μm, 19×150 mm; Mobile Phase, Water with 10 mmol NH4HCO3 and CH3CN (18% CH3CN up to 58% in 10 min, up to 95% in 1 min, down to 18% in 2 min); Detector, UV 254/220 nm. The fractions containing the pure product were concentrated and then redissolved in 5 mL of 12N hydrochloric acid. The resulting solution was concentrated under vacuum to afford 100 mg (47%) of N1-((3-(4-fluorophenyl)-1H-pyrazol-4-yl)methyl)-N1,N2-dimethylethane-1,2-diamine hydrochloride as a white solid. 1H NMR (300 MHz, D2O) δ: 7.91(s, 1H), 7.50-7.45 (m, 2H), 7.25-7.19 (m, 2H), 4.41 (s, 2H), 3.21 (s, 4H), 2.60 (s, 3H), 2.57 (s, 3H) ppm. LCMS (method J, ESI): RT=1.01 min, m/z=263.1 [M+H]+.

Workup

  1. customquenched by the addition of 10 mL of water
  2. extractionThe resulting mixture was extracted with 2×50 mL of dichloromethane
  3. dry with materialThe combined organic layers was dried over anhydrous sodium sulfate
  4. concentrationconcentrated under vacuum
  5. customThe residue was initially purified on a silica gel column
  6. washeluted with 10% MeOH in CH2Cl2
  7. customthe partially purified product was repurified by Prep-HPLC with the following conditions (1#-Pre-HPLC-005(Waters))
  8. waitup to 95% in 1 min
  9. waitdown to 18% in 2 min)
  10. additionThe fractions containing the pure product
  11. concentrationwere concentrated
  12. dissolutionredissolved in 5 mL of 12N hydrochloric acid
  13. concentrationThe resulting solution was concentrated under vacuum

Sources & evidence

ORD record
ord-cbfa8157831c457896c27ebd0f048bb7
Source dataset
uspto-grants-2016_05
Patent number
US09346761B2

Reaction notes

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