Triethylamine → Azd-8848

HRID 539251Notes

Reaction equation

HRID 539251 reaction equation
C(O)(=O)/C=C\C(O)=O.C(O)(=O)/C=C\C(O)=O.[NH2:17][C:18]1[N:26]=[C:25]([O:27][CH2:28][CH2:29][CH2:30][CH3:31])[N:24]=[C:23]2[C:19]=1[NH:20][C:21](=[O:45])[N:22]2[CH2:32][CH2:33][CH2:34][NH:35][CH2:36][CH2:37][CH2:38][N:39]1[CH2:44][CH2:43][O:42][CH2:41][CH2:40]1.C(N(CC)CC)C.C(O[BH3-])(=O)C.[Na+].[CH:59]([C:61]1[CH:62]=[C:63]([CH2:67][C:68]([O:70][CH3:71])=[O:69])[CH:64]=[CH:65][CH:66]=1)=O.C(=O)([O-])[O-].[Na+].[Na+]>CN1C(=O)CCC1.O>[NH2:17][C:18]1[N:26]=[C:25]([O:27][CH2:28][CH2:29][CH2:30][CH3:31])[N:24]=[C:23]2[C:19]=1[NH:20][C:21](=[O:45])[N:22]2[CH2:32][CH2:33][CH2:34][N:35]([CH2:59][C:61]1[CH:62]=[C:63]([CH2:67][C:68]([O:70][CH3:71])=[O:69])[CH:64]=[CH:65][CH:66]=1)[CH2:36][CH2:37][CH2:38][N:39]1[CH2:40][CH2:41][O:42][CH2:43][CH2:44]1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 10340Sodium Carbonate2×HCID 11819590Methyl 2-(3-formylphenyl)acetateHCID 23670382SodiumacetoxyborohydrideHCID 866513626-Amino-2-butoxy-9-{3-[(3-morpholin-4-ylpropyl)amino]propyl}-7,9-dihydro-8H-purine-8-one dimaleate

Product 1

HCID 11592228Azd-8848Yield 90.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
25 °C

Procedure

To a suspension of 6-amino-2-butoxy-9-{3-[(3-morpholin-4-ylpropyl)amino]propyl}-8-oxo-7,9-dihydro-8H-purine dimaleate (15.00 g, 23.45 mmol) in NMP (54.08 g) was added triethyamine (7.12 g, 70.35 mmol) at 25° C. Then sodium acetoxyborohydride (8.45 g, 39.87 mmol) was added thereto, followed by stirring at 25° C. for 15 minutes. After adding methyl (3-formylphenyl)acetate (6.27 g, 35.18 mol) and stirring at 25° C. for 8 hours, the mixture was cooled to 5° C. and then diluted with cold water (240.00). After adjusting pH to 7 with 10% sodium carbonate solution, a seed crystal was added thereto. After stirring for additional 15 minutes, the mixture was adjusted to pH 8 with 10% sodium carbonate solution and thereto was added water (15 g). After keeping at 5° C. for 1 hour, the resulting white solid was filtered, washed and dried to give the subject compound (12.10 g, 90.6%). The seed crystal used in the above was obtained by the method of the above example 5 without adding a seed crystal as the method of the above Example 5. Purity: 94.81% (HPLC)

Workup

  1. stirringstirring at 25° C. for 8 hours
  2. temperaturethe mixture was cooled to 5° C.
  3. additiona seed crystal was added
  4. stirringAfter stirring for additional 15 minutes
  5. waitAfter keeping at 5° C. for 1 hour
  6. filtrationthe resulting white solid was filtered
  7. washwashed
  8. customdried

Sources & evidence

ORD record
ord-beb3253802a940acbfc61d2df5d93aa8
Source dataset
uspto-grants-2014_10
Patent number
US08865896B2

Reaction notes

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