Propanal → 2-(4-(4-(7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)-1-propylpiperidin-4-yl)acetonitrile

HRID 1852986Notes

Reaction equation

HRID 1852986 reaction equation
Cl.[CH3:2][N:3]1[CH:7]=[C:6]([C:8]2[N:13]=[C:12]([C:14]3[CH:15]=[N:16][N:17]([C:19]4([CH2:25][C:26]#[N:27])[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]4)[CH:18]=3)[N:11]3[CH:28]=[CH:29][N:30]=[C:10]3[CH:9]=2)[CH:5]=[N:4]1.C(#N)C.C(N(CC)CC)C.[CH:41](=O)[CH2:42][CH3:43].[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C(=O)(O)[O-].[Na+].CCOC(C)=O>[CH3:2][N:3]1[CH:7]=[C:6]([C:8]2[N:13]=[C:12]([C:14]3[CH:15]=[N:16][N:17]([C:19]4([CH2:25][C:26]#[N:27])[CH2:20][CH2:21][N:22]([CH2:41][CH2:42][CH3:43])[CH2:23][CH2:24]4)[CH:18]=3)[N:11]3[CH:28]=[CH:29][N:30]=[C:10]3[CH:9]=2)[CH:5]=[N:4]1

Participants

8

Reactant 5

HCID 527PropanalHCID 6342AcetonitrileHCID 8471TriethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 67456826HCID 67456826, compound

Product 1

HCID 674576212-(4-(4-(7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)-1-propylpiperidin-4-yl)acetonitrileYield 27%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 516892Sodium BicarbonateSolvent

Procedure

2-(4-(4-(7-(1-Methyl-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)piperidin-4-yl)acetonitrile hydrochloride (Example 28, Step A; 30.0 mg, 0.0604 mmol) was suspended in acetonitrile (604 μL, 0.0604 mmol). To this was added triethylamine (33.7 μA, 0.242 mmol), followed by propionaldehyde (43.6 μL, 0.6043 mmol). After 30 minutes, NaBH(OAc)3 (64.0 mg, 0.302 mmol) was added. After stirring for 30 minutes, the reaction mixture was diluted in saturated sodium bicarbonate and EtOAc. The aqueous layer was back-extracted with DCM. The combined organic layers were washed with brine, dried with MgSO4, filtered and concentrated. Purification of the resulting crude material by reverse phase HPLC using a 0-100% acetonitrile/water gradient afforded afford 2-(4-(4-(7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)-1-propylpiperidin-4-yl)acetonitrile (7.0 mg, 23% yield). MS (apci) m/z=430.3 (M+H).

Workup

  1. extractionThe aqueous layer was back-extracted with DCM
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried with MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification of the resulting crude material by reverse phase HPLC
  7. customgradient afforded

Sources & evidence

ORD record
ord-f14e99262a80414e905d7550658a3287
Source dataset
uspto-grants-2015_02
Patent number
US08962596B2

Reaction notes

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