HCID 67006095, compound → HCID 57813352, compound

HRID 564603Notes

Reaction equation

HRID 564603 reaction equation
[CH2:1]([N:3]1[C:7]2=[N:8][C:9]([CH2:62][CH3:63])=[C:10]([CH2:19][NH:20][C:21]([C:23]3[CH:24]=[C:25]([C:29]([NH:31][CH2:32][C:33]4[CH:34]=[C:35]([C:41]5[CH:46]=[CH:45][CH:44]=[C:43]([CH2:47][N:48]6[CH2:54][CH2:53][CH2:52][N:51](C(OC(C)(C)C)=O)[CH2:50][CH2:49]6)[CH:42]=5)[CH:36]=[C:37]([O:39][CH3:40])[CH:38]=4)=[O:30])[CH:26]=[CH:27][CH:28]=3)=[O:22])[C:11]([NH:12][CH:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)=[C:6]2[CH:5]=[N:4]1)[CH3:2]>C(O)(C(F)(F)F)=O.C(Cl)Cl>[CH2:1]([N:3]1[C:7]2=[N:8][C:9]([CH2:62][CH3:63])=[C:10]([CH2:19][NH:20][C:21]([C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([NH:31][CH2:32][C:33]4[CH:34]=[C:35]([C:41]5[CH:46]=[CH:45][CH:44]=[C:43]([CH2:47][N:48]6[CH2:54][CH2:53][CH2:52][NH:51][CH2:50][CH2:49]6)[CH:42]=5)[CH:36]=[C:37]([O:39][CH3:40])[CH:38]=4)=[O:30])[CH:24]=3)=[O:22])[C:11]([NH:12][CH:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)=[C:6]2[CH:5]=[N:4]1)[CH3:2]

Participants

4

Reactant 1

HCID 67006095HCID 67006095, compound

Product 1

HCID 57813352HCID 57813352, compoundYield 31.2%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

236(b) A mixture of 1,1-dimethylethyl 4-{[3′-{[({3-[({[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)carbonyl]phenyl}carbonyl)-amino]methyl}-5′-(methyloxy)-3-biphenylyl]methyl}hexahydro-1H-1,4-diazepine-1-carboxylate (130 mg, 0.19 mmol) in 25% TFA in DCM (3 mL) was stirred at RT for 2 h. It was purified by preparative hplc (NH2OH condition), eluting with 10 to 90% CH3CN in water. The product-containing fractions were dried under GeneVac to give a solid. It was purified using a Gilson HPLC (with 0.1% TFA condition) and eluting with 10 to 90% CH3CN in water. Product-containing fractions were combined and then converted to the free base with saturated NaHCO3. The organic layer was dried over sodium sulfate, filtered and then concentrated to give N-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-N′-{[3′-(hexahydro-1H-1,4-diazepin-1-ylmethyl)-5-(methyloxy)-3-biphenylyl]methyl}-1,3-benzenedicarboxamide as a white solid (45 mg, 31%). LC-MS m/z 759 (M+H)+.

Workup

  1. customIt was purified by preparative hplc (NH2OH condition)
  2. washeluting with 10 to 90% CH3CN in water
  3. customThe product-containing fractions were dried under GeneVac
  4. customto give a solid
  5. customIt was purified
  6. washeluting with 10 to 90% CH3CN in water
  7. dry with materialThe organic layer was dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-bdb69ea3ba5e408f8dcd4f1c3b69a72b
Source dataset
uspto-grants-2011_11
Patent number
US08067408B2

Reaction notes

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