Formaldehyde → 2-(1-methyl-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 1852984Notes

Reaction equation

HRID 1852984 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)C.C(N(CC)CC)C.C=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C(=O)(O)[O-].[Na+].CCOC(C)=O>[CH3:31][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

Participants

8

Reactant 5

HCID 712FormaldehydeHCID 6342AcetonitrileHCID 8471TriethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 67456826HCID 67456826, compound

Product 1

HCID 674586762-(1-methyl-4-(4-(7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)piperidin-4-yl)acetonitrileYield 16%

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 (15.8 mg, 0.0318 mmol) was suspended in acetonitrile (318 μL, 0.0318 mmol). To this was added triethylamine (17.7 μL, 0.127 mmol) to freebase, followed by formaldehyde (25.8 mg, 0.318 mmol). After 30 minutes, NaBH(OAc)3 (33.7 mg, 0.159 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 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 2-(1-methyl-4-(4-(7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)piperidin-4-yl)acetonitrile (2.0 mg, 16% yield). MS (apci) m/z=402.1 (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

Sources & evidence

ORD record
ord-52fc0dea71ce4a2aa92f41adeff8f4d9
Source dataset
uspto-grants-2015_02
Patent number
US08962596B2

Reaction notes

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