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

HRID 1852985Notes

Reaction equation

HRID 1852985 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:31](#N)[CH3:32].C(N(CC)CC)C.C(=O)C.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C(=O)(O)[O-].CCOC(C)=O>[CH2:31]([N:22]1[CH2:21][CH2:20][C:19]([CH2:25][C:26]#[N:27])([N:17]2[CH:18]=[C:14]([C:12]3[N:11]4[CH:28]=[CH:29][N:30]=[C:10]4[CH:9]=[C:8]([C:6]4[CH:5]=[N:4][N:3]([CH3:2])[CH:7]=4)[N:13]=3)[CH:15]=[N:16]2)[CH2:24][CH2:23]1)[CH3:32]

Participants

8

Reactant 5

HCID 177AcetaldehydeHCID 6342AcetonitrileHCID 8471TriethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 67456826HCID 67456826, compound

Product 1

HCID 866853092-(1-ethyl-4-(4-(7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)piperidin-4-yl)acetonitrileYield 26.2%

Reagents, catalysts & solvents 2

HCID 769Bicarbonate IonSolventHCID 8857Ethyl AcetateSolvent

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; 27.0 mg, 0.0543 mmol) was suspended in acetonitrile (543 μL, 0.0543 mmol). To this was added triethylamine (30.3 μL, 0.217 mmol) to freebase, followed by acetaldehyde (30.5 μL, 0.543 mmol). After 30 minutes, NaBH(OAc)3 (57.6 mg, 0.272 mmol) was added to reduce. After stirring for 30 minutes, the reaction mixture was diluted in saturated bicarbonate and EtOAc. The aqueous layer was back-extracted with DCM. The combined organic layer was 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-(1-ethyl-4-(4-(7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)piperidin-4-yl)acetonitrile (5.9 mg, 26% yield). MS (apci) m/z=416.2 (M+H).

Workup

  1. extractionThe aqueous layer was back-extracted with DCM
  2. washThe combined organic layer was 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-411a28a4cf764084be8944435b3f94b6
Source dataset
uspto-grants-2015_02
Patent number
US08962596B2

Reaction notes

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