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

HRID 1846543Notes

Reaction equation

HRID 1846543 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.[CH:37]1([CH2:40][C:41](O)=O)[CH2:39][CH2:38]1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C(O)(=O)C>CN(C=O)C>[CH:37]1([CH2:40][C:41]2[NH:1][C:2]3[CH:3]=[C:4]([O:5][C:6]4[N:11]=[CH:10][N:9]=[C:8]([N:12]5[CH2:13][CH2:14][CH:15]([N:18]6[CH2:24][CH2:23][C:22]7[CH:25]=[C:26]([O:29][CH3:30])[CH:27]=[CH:28][C:21]=7[NH:20][C:19]6=[O:31])[CH2:16][CH2:17]5)[CH:7]=4)[CH:32]=[C:33]([CH3:36])[C:34]=3[N:35]=2)[CH2:39][CH2:38]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 138440Cyclopropaneacetic 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 462446763-{1-[6-(2-cyclopropylmethyl-7-methyl-3H-benzimidazol-5-yloxy)-pyrimidin-4-yl]-piperidin-4-yl}-7-methoxy-1,3,4,5-tetrahydro-benzo[d][1,3]diazepin-2-one

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, 46 mg (0.46 mmol) cyclopropyl-acetic acid, 151 mg (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. In addition the reaction mixture was 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. additionIn addition the reaction mixture
  2. stirringwas stirred for 1 h at 100° C.
  3. temperaturecooled
  4. custompurified by preparative HPLC-MS
  5. customthe acetonitrile was evaporated down
  6. customthe precipitate formed
  7. filtrationfiltered
  8. washwashed with water
  9. customdried under HV

Sources & evidence

ORD record
ord-cbba410d95704ec09917d0c24ee01f0d
Source dataset
uspto-grants-2015_02
Patent number
US08952014B2

Reaction notes

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