Acetic Acid → 1-[1-(1-tert-butoxycarbonyl-4-piperidinyl)-4-piperidinyl]-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine

HRID 432137Notes

Reaction equation

HRID 432137 reaction equation
[O:1]([C:8]1[CH:13]=[CH:12][C:11]([C:14]2[C:22]3[C:17](=[N:18][CH:19]=[N:20][C:21]=3[NH2:23])[N:16]([CH:24]3[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]3)[N:15]=2)=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:30]([O:34][C:35]([N:37]1[CH2:42][CH2:41][C:40](=O)[CH2:39][CH2:38]1)=[O:36])([CH3:33])([CH3:32])[CH3:31].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(=O)C.C(=O)(O)[O-].[Na+]>O.ClCCCl>[C:30]([O:34][C:35]([N:37]1[CH2:42][CH2:41][CH:40]([N:27]2[CH2:28][CH2:29][CH:24]([N:16]3[C:17]4=[N:18][CH:19]=[N:20][C:21]([NH2:23])=[C:22]4[C:14]([C:11]4[CH:10]=[CH:9][C:8]([O:1][C:2]5[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=5)=[CH:13][CH:12]=4)=[N:15]3)[CH2:25][CH2:26]2)[CH2:39][CH2:38]1)=[O:36])([CH3:33])([CH3:31])[CH3:32]

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 516892Sodium BicarbonateHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 5049666Sodium triacetoxyborohydrideHCID 223472623-(4-phenoxyphenyl)-1-(piperidin-4-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine2×

Product 1

HCID 223473271-[1-(1-tert-butoxycarbonyl-4-piperidinyl)-4-piperidinyl]-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amineYield 49.2%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 962WaterSolvent

Procedure

3-(4-phenoxyphenyl)-1-(4-piperidyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (Compound 2) (350 mg, 0.906 mmol), 1-tert-butoxycarbonyl-4-piperidone(198mg, 0.996 mmol), sodium triacetoxyborohydride (288 mg, 1.358 mmol) and glacial acetic acid(60 ul, 0.996 mmol) were mixed with 5 ml of 1,2-dichloroethane. After stirring at room temperature overnight, 2 ml of water was added followed by solid sodium bicarbonate until the pH reached about 8. The layers were separated and the aqueous layer was extracted with dichloromethane. The combined organic layer was washed, dried and evaporated. The residue was purified via flash column chromatography to give 254 mg of 1-[1-(1-tert-butoxycarbonyl-4-piperidyl)-4-piperidyl]-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine. 1H NMR (DMSO) 1.39(m, 13H), 1.75 (m, 2H), 1.91 (m, 2H), 2.17(m, 2H), 2.35 (m, 2H), 2.72 (m, 2H), 3.0 (m, 2H), 3.63 (m, 1H), 3.98 (m, 2H), 4.63 (m, 1H), 7.16 (m, 5H), 7.44 (m, 2H), 7.67 (d, J=8.60 Hz, 2H), 8.23 (s, 1H); LC/MS (MH+32 484).

Workup

  1. customThe layers were separated
  2. extractionthe aqueous layer was extracted with dichloromethane
  3. washThe combined organic layer was washed
  4. customdried
  5. customevaporated
  6. customThe residue was purified via flash column chromatography

Sources & evidence

ORD record
ord-28636b4b839f4eb993300cea49e87976
Source dataset
uspto-grants-2003_12
Patent number
US06660744B1

Reaction notes

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