Sodium Hydroxide → HCID 42641523, compound

HRID 2067011Notes

Reaction equation

HRID 2067011 reaction equation
CO[C:3]([C:5]1[CH:10]=[CH:9][N:8]2[CH:11]=[N:12][CH:13]=[C:7]2[C:6]=1[NH:14][C:15]1[CH:20]=[CH:19][C:18]([CH:21]2[CH2:23][CH2:22]2)=[CH:17][C:16]=1[F:24])=[O:4].[OH-].[Na+].[Cl-].[NH4+].C[N:30](C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CO.ClCCl>[CH:21]1([C:18]2[CH:19]=[CH:20][C:15]([NH:14][C:6]3[C:7]4[N:8]([CH:11]=[N:12][CH:13]=4)[CH:9]=[CH:10][C:5]=3[C:3]([NH2:30])=[O:4])=[C:16]([F:24])[CH:17]=2)[CH2:22][CH2:23]1

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 25517Ammonium ChlorideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 595651918-(4-Cyclopropyl-2-fluoro-phenylamino)-imidazo[1,5-a]pyridine-7-carboxylic acid methyl ester

Product 1

HCID 42641523HCID 42641523, compoundYield 23%

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 6344DichloromethaneSolvent

Conditions

Temperature
65 °C

Procedure

To a solution of 8-(4-cyclopropyl-2-fluoro-phenylamino)-imidazo[1,5-a]pyridine-7-carboxylic acid methyl ester (23 mg, 0.07 mmol) in IMS (1.0 mL) was added a 1.0 M aqueous solution of sodium hydroxide (0.10 mL, 0.10 mmol). The reaction mixture was heated to 65° C. for 1 hour and then cooled to room temperature and concentrated in vacuo. The resulting residue was azeotroped with toluene, and then dissolved in DMF (1 mL). Ammonium chloride (7 mg, 0.13 mmol), N-N-diisopropylethylamine (47 uL, 0.27 mmol) and HATU (51 mg, 0.13 mmol) were added sequentially, before the reaction mixture was stirred for 18 hours at room temperature. The reaction mixture was then diluted with methanol and loaded onto an Isolute® SCX-2 cartridge (5 g). The cartridge was then washed with methanol and the desired product was subsequently eluted using 2M NH3 in MeOH. The eluent was collected and concentrated to give a residue. The residue was subjected to flash chromatography (Si-PPC, gradient 0% to 5%, methanol in dichloromethane) to afford the title compound as a pale yellow solid (5 mg, 23%). LCMS (method A): RT=6.64 min, [M+H]+=311. 1H NMR (CD3OD) 8.18 (1H, d, J=0.88 Hz), 7.64 (1H, dd, J=7.40, 0.97 Hz), 7.13 (1H, t, J=8.28 Hz), 6.93-6.86 (3 H, m), 6.35 (1H, s), 1.98-1.90 (1 H, m), 1.05-0.97 (2 H, m), 0.73-0.68 (2H, m).

Workup

  1. temperaturecooled to room temperature
  2. concentrationconcentrated in vacuo
  3. customThe resulting residue was azeotroped with toluene
  4. dissolutiondissolved in DMF (1 mL)
  5. washThe cartridge was then washed with methanol
  6. washthe desired product was subsequently eluted
  7. customThe eluent was collected
  8. concentrationconcentrated
  9. customto give a residue

Sources & evidence

ORD record
ord-a7c552076eaf44b1b122a73124b64619
Source dataset
uspto-grants-2012_10
Patent number
US08293763B2

Reaction notes

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