Sodium Hydroxide → (E)-3-(4-(5-cyclopropyl-1H-pyrazol-3-ylamino)-2-phenylpyrimidin-5-yl)prop-2-en-1-ol

HRID 1484866Notes

Reaction equation

HRID 1484866 reaction equation
[H-].C([Al+]CC(C)C)C(C)C.C([N:14]1[C:18]([CH:19]2[CH2:21][CH2:20]2)=[CH:17][C:16]([NH:22][C:23]2[C:28](/[CH:29]=[CH:30]/[C:31](OC)=[O:32])=[CH:27][N:26]=[C:25]([C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)[N:24]=2)=[N:15]1)(=O)C.[H-].[OH-].[Na+]>C1COCC1.CCCCCC>[CH:19]1([C:18]2[NH:14][N:15]=[C:16]([NH:22][C:23]3[C:28](/[CH:29]=[CH:30]/[CH2:31][OH:32])=[CH:27][N:26]=[C:25]([C:35]4[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=4)[N:24]=3)[CH:17]=2)[CH2:21][CH2:20]1

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 166653HydrideHCID 21225700DiisobutylaluminumhydrideHCID 66927424(E)-methyl 3-(4-(1-acetyl-5-cyclopropyl-1H-pyrazol-3-ylamino)-2-phenylpyrimidin-5-yl)acrylate

Product 1

HCID 58169182(E)-3-(4-(5-cyclopropyl-1H-pyrazol-3-ylamino)-2-phenylpyrimidin-5-yl)prop-2-en-1-olYield 96.8%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Conditions

Temperature
-78 °C

Procedure

A hexane solution of diisobutylaluminum hydride (1 mL of a 1.0M solution, 1.0 mmol, 4.0 equiv.) was added to a cooled (−78° C.) solution of (E)-methyl 3-(4-(1-acetyl-5-cyclopropyl-1H-pyrazol-3-ylamino)-2-phenylpyrimidin-5-yl)acrylate (100 mg, 0.248 mmol, 1.0 equiv.) in THF (2 mL). After stirring for 1 h at −78° C., additional disobutylalumium hydride solution (0.25 mL of a 1.0M solution, 0.25 mmol, 1.0 equiv.) was added. After another 30 min, NaOH solution (1N) was added and the reaction mixture was allowed to warm slowly to room temperature for 10 min. The organic layers were separated and the aqueous phase was extracted with CH2Cl2. The combined organic layers were washed with water, brine, dried (Na2SO4) and filtered. The filtrate was concentrated to afford crude. The crude was crystallized with ethanol to afford compound (E)-3-(4-(5-cyclopropyl-1H-pyrazol-3-ylamino)-2-phenylpyrimidin-5-yl)prop-2-en-1-ol (Compound 53) (80 mg, 96%). LC-MS (m/z): 334.1 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ 0.71-0.72 (m, 2H), 0.96-0.98 (m, 2H), 1.91-1.98 (m, 1H), 4.15 (t, J=5.2 Hz, 2H), 4.87 (m, 1H), 6.34 (dt, J1=4.8 Hz, J2=15.6 Hz, 1H), 6.48 (s, 1H), 6.80 (d, J=16 Hz, 1H), 7.48-7.51 (m, 3H), 8.28-8.30 (m, 2H), 8.47 (s, 1H), 9.05 (s, 1H), 12.15 (s, 1H).

Workup

  1. waitAfter another 30 min
  2. temperatureto warm slowly to room temperature for 10 min
  3. customThe organic layers were separated
  4. extractionthe aqueous phase was extracted with CH2Cl2
  5. washThe combined organic layers were washed with water, brine
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationThe filtrate was concentrated
  9. customto afford crude
  10. customThe crude was crystallized with ethanol

Sources & evidence

ORD record
ord-312b36d1ca894e5daefbdede12f5e4ef
Source dataset
uspto-grants-2016_08
Patent number
US09422271B2

Reaction notes

Loading…