Sodium hydride → HCID 118253053, compound

HRID 1770804Notes

Reaction equation

HRID 1770804 reaction equation
[CH3:1][CH:2]([N:4]1[C:8]([C:9]2[C:14]([CH2:15][OH:16])=[CH:13][CH:12]=[CH:11][N:10]=2)=[CH:7][CH:6]=[N:5]1)[CH3:3].[H-].[Na+].Cl[C:20]1[CH:25]=[CH:24][N:23]=[C:22]([NH:26][CH3:27])[C:21]=1[CH:28]=[O:29]>CN(C)C=O>[CH:2]([N:4]1[C:8]([C:9]2[C:14]([CH2:15][O:16][C:20]3[C:21]([CH:28]=[O:29])=[C:22]([NH:26][CH3:27])[N:23]=[CH:24][CH:25]=3)=[CH:13][CH:12]=[CH:11][N:10]=2)=[CH:7][CH:6]=[N:5]1)([CH3:1])[CH3:3]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 896547582-(1-(1-Methylethyl)-1H-pyrazol-5-yl)-3-pyridinemethanolHCID 90461750HCID 90461750, compound

Product 1

HCID 118253053HCID 118253053, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

Steps 3 & 4. Into a 100-mL round-bottom flask, was placed a solution of [2-[1-(propan-2-yl)-1H-pyrazol-5-yl]pyridin-3-yl]methanol (1.15 g, 5.29 mmol, 1.00 equiv) in N,N-dimethylformamide (40 mL). This was followed by the addition of sodium hydride (530 mg, 13.25 mmol, 2.50 equiv, 60%) at 0° C. The mixture was stirred for 15 min at 0° C. To this was added 4-chloro-2-(methylamino)pyridine-3-carbaldehyde (900 mg, 5.28 mmol, 1.00 equiv). The resulting solution was stirred overnight at room temperature. The reaction was then quenched by the addition of 30 mL of water. The resulting solution was extracted with 5×30 mL of ethyl acetate and the organic layers combined and concentrated under vacuum. The crude product (300 mg) was purified by Prep-HPLC with the following conditions (Prep-HPLC-020): Column, SunFire Prep C18 OBD Column, 5 um, 19*100 mm, mobile phase, water with 0.1% TFA and MeCN (3.0% MeCN up to 20.0% in 5 min, up to 95.0% in 2 min, down to 3.0% in 1 min); Detector, waters 2489 254&220 nm. This resulted in 107.1 mg (6%) of 2-(methylamino)-4-([2-[1-(propan-2-yl)-1H-pyrazol-5-yl]pyridin-3-yl]methoxy)pyridine-3-carbaldehyde as a yellow solid. 1HNMR (400 MHz, DMSO, ppm): 8.72 (m, 1H), 8.17 (s, 1H), 7.91 (m, 1H), 7.52 (m, 3H), 6.56 (s, 1H), 6.26 (d, J=4.2 Hz, 1H), 6.15 (d, J=3.3 Hz, 1H), 5.43 (m, 1H), 5.12 (m, 1H), 4.60 (m, 1H), 2.87 (d, J=3.3 Hz, 1H), 1.46 (d, J=5.1 Hz, 1H), 1.35 (d, J=5.1 Hz, 1H); (ES, m/z): 352.1 [M+1]+

Workup

  1. customInto a 100-mL round-bottom flask, was placed
  2. stirringThe resulting solution was stirred overnight at room temperature
  3. customThe reaction was then quenched by the addition of 30 mL of water
  4. extractionThe resulting solution was extracted with 5×30 mL of ethyl acetate
  5. concentrationconcentrated under vacuum
  6. customThe crude product (300 mg) was purified by Prep-HPLC with the following conditions (Prep-HPLC-020)
  7. waitColumn, SunFire Prep C18 OBD Column, 5 um, 19*100 mm, mobile phase, water with 0.1% TFA and MeCN (3.0% MeCN up to 20.0% in 5 min
  8. waitup to 95.0% in 2 min
  9. waitdown to 3.0% in 1 min)
  10. customThis resulted in 107.1 mg (6%) of 2-(methylamino)-4-([2-[1-(propan-2-yl)-1H-pyrazol-5-yl]pyridin-3-yl]methoxy)pyridine-3-carbaldehyde as a yellow solid

Sources & evidence

ORD record
ord-a469bba38b5a47ee9138fff4f800b572
Source dataset
uspto-grants-2016_02
Patent number
US09248199B2

Reaction notes

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