N,N-Dimethyl-1,3-propanediamine → HCID 44546732, compound

HRID 1676816Notes

Reaction equation

HRID 1676816 reaction equation
[F:1][C:2]1([F:36])[CH2:8][N:7]([CH2:9][CH2:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[C:6]2[N:18]=[C:19]([NH:22][C:23]3[CH:31]=[CH:30][C:26]([C:27]([OH:29])=O)=[CH:25][C:24]=3[O:32][CH3:33])[N:20]=[CH:21][C:5]=2[N:4]([CH3:34])[C:3]1=[O:35].C(N(C(C)C)C(C)C)C.[CH3:46][N:47]([CH3:52])[CH2:48][CH2:49][CH2:50][NH2:51]>CN(C)C=O>[F:1][C:2]1([F:36])[CH2:8][N:7]([CH2:9][CH2:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[C:6]2[N:18]=[C:19]([NH:22][C:23]3[CH:31]=[CH:30][C:26]([C:27]([NH:51][CH2:50][CH2:49][CH2:48][N:47]([CH3:52])[CH3:46])=[O:29])=[CH:25][C:24]=3[O:32][CH3:33])[N:20]=[CH:21][C:5]=2[N:4]([CH3:34])[C:3]1=[O:35]

Participants

5

Reactant 3

HCID 7993N,N-Dimethyl-1,3-propanediamineHCID 81531DiisopropylethylamineHCID 44549065HCID 44549065, compound

Product 1

HCID 44546732HCID 44546732, compoundYield 34.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of 0.05 g (0.10 mmole) of 4-[7,7-difluoro-5-methyl-6-oxo-9-(3-phenyl-propyl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino]-3-methoxy-benzoic acid (I-281), 0.07 mL (0.40 mmole) of ethyldiisopropyl amine and 0.0074 g (0.11 mmole) of N,N-dimethyl-propane-1,3-diamine in 2.0 mL of dimethylformamide was added 0.048 g (0.11 mmole) of 1-(di-1-pyrrolidinylmethylene)-1H-benzotriazolium 3-oxide hexafluorophosphate. The mixture was stirred at room temperature for 1 hour, then diluted with 10 mL of ice water. The mixture was extracted three times with dichloromethane. The combined organic layers were washed three times with sodium carbonate, three times with brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. Purification by silica gel chromatography, eluting with dichloromethane-methanol (gradient, 100:0-40:60) gave 0.020 g of 4-[7,7-difluoro-5-methyl-6-oxo-9-(3-phenyl-propyl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino]-N-(3-dimethylamino-propyl)-3-methoxy-benzamide (I-285) as a white solid.

Workup

  1. extractionThe mixture was extracted three times with dichloromethane
  2. washThe combined organic layers were washed three times with sodium carbonate, three times with brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customPurification by silica gel chromatography
  7. washeluting with dichloromethane-methanol (gradient, 100:0-40:60)

Sources & evidence

ORD record
ord-94b9b532d50a421c8cc8fa7242c61212
Source dataset
uspto-grants-2011_08
Patent number
US08003785B2

Reaction notes

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