2-Fluoroethanol → HCID 178424913, compound

HRID 80852

Reaction equation

HRID 80852 reaction equation
Cl[C:2]1[C:3]2[CH2:24][N:23]([C:25]3[CH:30]=[C:29]([CH:31]([CH3:33])[CH3:32])[CH:28]=[CH:27][C:26]=3[CH3:34])[CH2:22][CH2:21][C:4]=2[N:5]=[C:6]([C:8]2[C:16]([CH3:17])=[CH:15][CH:14]=[C:13]3[C:9]=2[C:10]([CH3:20])=[N:11][N:12]3C=O)[N:7]=1.[F:35][CH2:36][CH2:37][OH:38].[H-].[Na+]>C1COCC1>[CH3:20][C:10]1[C:9]2[C:13](=[CH:14][CH:15]=[C:16]([CH3:17])[C:8]=2[C:6]2[N:7]=[C:2]([O:38][CH2:37][CH2:36][F:35])[C:3]3[CH2:24][N:23]([C:25]4[CH:30]=[C:29]([CH:31]([CH3:32])[CH3:33])[CH:28]=[CH:27][C:26]=4[CH3:34])[CH2:22][CH2:21][C:4]=3[N:5]=2)[NH:12][N:11]=1

Participants

5

Reactant 3

HCID 97372-FluoroethanolHCID 24758Sodium hydrideHCID 866902884-(4-chloro-6-(5-isopropyl-2-methylphenyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-3,5-dimethyl-1H-indazole-1-carbaldehyde

Product 1

HCID 178424913HCID 178424913, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4-(4-chloro-6-(5-isopropyl-2-methylphenyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-3,5-dimethyl-1H-indazole-1-carbaldehyde (30 mg, 0.063 mmol) in THF (3 mL) was added 2-fluoroethanol (16.2 mg, 0.25 mmol) and NaH (15.1 mg, 0.63 mmol, 60% in mineral oil). The mixture was stirred at room temperature for 4 h. LC-MS showed reaction complete. The reaction mixture was concentrated and the residue was partitioned between saturated aqueous NH4Cl solution and DCM. The layers were separated and the aqueous layer was extracted further with DCM. The organics were combined and concentrated. The residue was purified by FCC (0-100% EtOAc/heptane) to provide 2-(3,5-dimethyl-1H-indazol-4-yl)-4-(2-fluoroethoxy)-6-(5-isopropyl-2-methylphenyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine. 1H NMR (400 MHz, METHANOL-d4) δ ppm 7.47 (d, J=8.59 Hz, 1H), 7.34 (s, 1H), 7.15 (d, J=7.71 Hz, 1H), 7.06 (d, J=1.39 Hz, 1H), 6.92 (dd, J=1.52, 7.71 Hz, 1H), 4.71-4.81 (m, 2H), 4.67 (s, 2H), 4.13 (s, 2H), 3.33-3.39 (m, 2H), 3.05 (t, J=5.56 Hz, 2H), 2.88 (td, J=6.93, 13.80 Hz, 1H), 2.32 (s, 3H), 2.27 (s, 3H), 1.98 (s, 3H), 1.25 (d, J=6.82 Hz, 6H); MS (ESE) m/z 474.4 (M+H)+.

Workup

  1. customreaction complete
  2. concentrationThe reaction mixture was concentrated
  3. customthe residue was partitioned between saturated aqueous NH4Cl solution and DCM
  4. customThe layers were separated
  5. extractionthe aqueous layer was extracted further with DCM
  6. concentrationconcentrated
  7. customThe residue was purified by FCC (0-100% EtOAc/heptane)

Sources & evidence

ORD record
ord-04b0c18196cf48118e1f05072d283ab4
Source dataset
uspto-grants-2014_09
Patent number
US08846656B2

Linked notes

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