Acetic Acid → HCID 67006095, compound

HRID 564602Notes

Reaction equation

HRID 564602 reaction equation
[CH2:1]([N:3]1[C:7]2=[N:8][C:9]([CH2:49][CH3:50])=[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]([CH:47]=O)[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].[N:51]1([C:58]([O:60][C:61]([CH3:64])([CH3:63])[CH3:62])=[O:59])[CH2:57][CH2:56][CH2:55][NH:54][CH2:53][CH2:52]1.CC(O)=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C(Cl)Cl>[CH2:1]([N:3]1[C:7]2=[N:8][C:9]([CH2:49][CH3:50])=[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:54]6[CH2:55][CH2:56][CH2:57][N:51]([C:58]([O:60][C:61]([CH3:64])([CH3:63])[CH3:62])=[O:59])[CH2:52][CH2:53]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]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 2756058Tert-butyl 1,4-diazepane-1-carboxylate2×HCID 5049666Sodium triacetoxyborohydride2×HCID 57813270HCID 57813270, compound

Product 1

HCID 67006095HCID 67006095, compoundYield 80.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

236(a) To a solution of N-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-N′-{[3′-formyl-5-(methyloxy)-3-biphenylyl]methyl}-1,3-benzenedicarboxamide (130 mg, 0.19 mmol) in DCM (2 mL) was added tert-butyl 1-homopiperazine carboxylate (0.04 mL, 0.21 mmol), AcOH (0.01 mL, 0.23 mmol) followed by NaBH(OAc)3 (57.2 mg, 0.27 mmol). The reaction mixture was stirred at RT overnight. LC-MS showed minor amount of starting material remaining so 0.5 equiv. of tert-butyl 1-homopiperazine carboxylate and 1 equiv of NaBH(OAc)3 were added to the mixture. It was stirred for an additional 4 h. LC-MS showed no more starting material. The reaction was quenched with saturated NaHCO3 and extracted with DCM twice. The combined organic layers were washed with brine and then concentrated under vacuum to give a crude residue. It was purified with CombiFlash chromatography, eluting with 0 to 10% MeOH (2M NH3 in MeOH) in DCM. The product fractions were combined and concentrated under vacuum to give 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 (131 mg, 79%). LC-MS m/z 859 (M+H)+.

Workup

  1. additionwere added to the mixture
  2. stirringIt was stirred for an additional 4 h
  3. customThe reaction was quenched with saturated NaHCO3
  4. extractionextracted with DCM twice
  5. washThe combined organic layers were washed with brine
  6. concentrationconcentrated under vacuum
  7. customto give a crude residue
  8. customIt was purified with CombiFlash chromatography
  9. washeluting with 0 to 10% MeOH (2M NH3 in MeOH) in DCM
  10. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-867b65212a54407b8349443ef9e6083e
Source dataset
uspto-grants-2011_11
Patent number
US08067408B2

Reaction notes

Loading…