Sodium Hydroxide → (S)-2,4-Diamino-6-((1-(3-hydroxy-1-methyl-6-morpholino-1H-pyrrolo[3,2-b]pyridin-5-yl)ethyl)amino)pyrimidine-5-carbonitrile

HRID 75345Notes

Reaction equation

HRID 75345 reaction equation
[OH-].[Na+].C([O:6][C:7]1[C:11]2=[N:12][C:13]([C@@H:22]([NH:24][C:25]3[C:30]([C:31]#[N:32])=[C:29]([NH2:33])[N:28]=[C:27]([NH2:34])[N:26]=3)[CH3:23])=[C:14]([N:16]3[CH2:21][CH2:20][O:19][CH2:18][CH2:17]3)[CH:15]=[C:10]2[N:9]([CH3:35])[CH:8]=1)(=O)C.C(=O)(O)[O-].[Na+]>CO>[NH2:34][C:27]1[N:28]=[C:29]([NH2:33])[C:30]([C:31]#[N:32])=[C:25]([NH:24][C@H:22]([C:13]2[N:12]=[C:11]3[C:7]([OH:6])=[CH:8][N:9]([CH3:35])[C:10]3=[CH:15][C:14]=2[N:16]2[CH2:21][CH2:20][O:19][CH2:18][CH2:17]2)[CH3:23])[N:26]=1

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 516892Sodium BicarbonateHCID 86708017(S)-5-(1-((2,6-Diamino-5-cyanopyrimidin-4-yl)amino)ethyl)-1-methyl-6-morpholino-1H-pyrrolo[3,2-b]pyridin-3-yl acetate

Product 1

HCID 73056004(S)-2,4-Diamino-6-((1-(3-hydroxy-1-methyl-6-morpholino-1H-pyrrolo[3,2-b]pyridin-5-yl)ethyl)amino)pyrimidine-5-carbonitrileYield 7.04%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

1N NaOH was added to a 50 mL pear flask charged with (S)-5-(1-((2,6-diamino-5-cyanopyrimidin-4-yl)amino)ethyl)-1-methyl-6-morpholino-1H-pyrrolo[3,2-b]pyridin-3-yl acetate (3.29 g, 7.29 mmol) in methanol (25 mL). The reaction was complete within about 15 minutes. Saturated sodium bicarbonate solution was added. The aqueous layer was extracted with EtOAc (3×). The combined organic layers were dried over MgSO4, filtered, and concentrated. The crude product was purified by preparative HPLC (acid mode, 5% to 25% ACN/water gradient). The product-containing fractions were pooled, neutralized with saturated sodium bicarbonate, and then extracted with EtOAc (3×). The combined organic layers were dried over MgSO4, filtered, and concentrated to give the title compound as an off-white solid (210 mg, 7.04%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.34 (d, J=6.57 Hz, 3 H), 2.70-2.80 (m, 2 H), 2.96-3.07 (m, 2 H), 3.15 (s, 3 H), 3.63 (d, J=2.53 Hz, 2 H), 3.71-3.88 (m, 4 H), 5.78-5.96 (m, 1 H), 6.07 (s, 1 H), 6.41 (br s, 2 H), 6.60 (s, 2 H), 7.33 (s, 1 H); ESI-MS m/z [M+H]+ calc'd for C19H23N9O2, 410; found 410.

Workup

  1. extractionThe aqueous layer was extracted with EtOAc (3×)
  2. dry with materialThe combined organic layers were dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude product was purified by preparative HPLC (acid mode, 5% to 25% ACN/water gradient)
  6. extractionextracted with EtOAc (3×)
  7. dry with materialThe combined organic layers were dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-2a66e3de34fa455a94b5e54b9c549aee
Source dataset
uspto-grants-2014_09
Patent number
US08835420B2

Reaction notes

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