Acetic Acid → (6-{6-[4-(7-methoxy-2-oxo-1,2,4,5-tetrahydro-benzo[d][1,3]diazepin-3-yl)-piperidin-1-yl]-pyrimidin-4-yloxy}-4-methyl-1H-benzimidazole-2-yl)-acetonitrile

HRID 1846538Notes

Reaction equation

HRID 1846538 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([CH:32]=[C:33]([CH3:36])[C:34]=1[NH2:35])[O:5][C:6]1[N:11]=[CH:10][N:9]=[C:8]([N:12]2[CH2:17][CH2:16][CH:15]([N:18]3[CH2:24][CH2:23][C:22]4[CH:25]=[C:26]([O:29][CH3:30])[CH:27]=[CH:28][C:21]=4[NH:20][C:19]3=[O:31])[CH2:14][CH2:13]2)[CH:7]=1.[C:37]([CH2:39][C:40](O)=O)#[N:38].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C(O)(=O)C>CN(C=O)C>[CH3:30][O:29][C:26]1[CH:27]=[CH:28][C:21]2[NH:20][C:19](=[O:31])[N:18]([CH:15]3[CH2:14][CH2:13][N:12]([C:8]4[N:9]=[CH:10][N:11]=[C:6]([O:5][C:4]5[CH:32]=[C:33]([CH3:36])[C:34]6[N:35]=[C:40]([CH2:39][C:37]#[N:38])[NH:1][C:2]=6[CH:3]=5)[CH:7]=4)[CH2:17][CH2:16]3)[CH2:24][CH2:23][C:22]=2[CH:25]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 9740Cyanoacetic acidHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 669783753-{1-[6-(3,4-Diamino-5-methyl-phenoxy)-pyrimidin-4-yl]-piperidin-4-yl}-7-methoxy-1,3,4,5-tetrahydro-benzo[d][1,3]diazepin-2-one

Product 1

HCID 46244595(6-{6-[4-(7-methoxy-2-oxo-1,2,4,5-tetrahydro-benzo[d][1,3]diazepin-3-yl)-piperidin-1-yl]-pyrimidin-4-yloxy}-4-methyl-1H-benzimidazole-2-yl)-acetonitrile

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

0.20 g (0.42 mmol) 3-{1-[6-(3,4-diamino-5-methyl-phenoxy)-pyrimidin-4-yl]-piperidin-4-yl}-7-methoxy-1,3,4,5-tetrahydro-benzo[d][1,3]diazepin-2-one, 40 mg (0.46 mmol) cyanoacetic acid, 0.15 g (0.47 mmol) TBTU and 0.14 mL (1.00 mmol) TEA in 2.00 mL DMF were stirred for 4 h at RT. Then 2.00 mL glacial acetic acid was added and the mixture was stirred overnight at RT. The reaction mixture was also stirred for 1 h at 100° C., then cooled and purified by preparative HPLC-MS. The product-containing fractions were combined and the acetonitrile was evaporated down. The residue was made alkaline with 4N aqueous sodium hydroxide solution, the precipitate formed was suction filtered, washed with water and dried under HV.

Workup

  1. stirringThe reaction mixture was also stirred for 1 h at 100° C.
  2. temperaturecooled
  3. custompurified by preparative HPLC-MS
  4. customthe acetonitrile was evaporated down
  5. customthe precipitate formed
  6. filtrationfiltered
  7. washwashed with water
  8. customdried under HV

Sources & evidence

ORD record
ord-f4813ed7746c42379db6908eebfdaea8
Source dataset
uspto-grants-2015_02
Patent number
US08952014B2

Reaction notes

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