Formaldehyde → N-[3-(3-{2-[(2-methyl-1,2,3,4-tetrahydro-7-isoquinolinyl)amino]-4-pyrimidinyl}pyrazolo[1,5-a]pyridin-2-yl)phenyl]benzamide

HRID 1159896Notes

Reaction equation

HRID 1159896 reaction equation
[CH2:1]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([NH:11][C:12]3[N:17]=[C:16]([C:18]4[C:19]([C:27]5[CH:28]=[C:29]([NH:33][C:34](=[O:41])[C:35]6[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=6)[CH:30]=[CH:31][CH:32]=5)=[N:20][N:21]5[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=45)[CH:15]=[CH:14][N:13]=3)[CH:9]=2)[CH2:4][CH2:3][NH:2]1.[CH2:42](Cl)Cl.CO.C=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(O)(=O)C>[CH3:42][N:2]1[CH2:3][CH2:4][C:5]2[C:10](=[CH:9][C:8]([NH:11][C:12]3[N:17]=[C:16]([C:18]4[C:19]([C:27]5[CH:28]=[C:29]([NH:33][C:34](=[O:41])[C:35]6[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=6)[CH:30]=[CH:31][CH:32]=5)=[N:20][N:21]5[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=45)[CH:15]=[CH:14][N:13]=3)=[CH:7][CH:6]=2)[CH2:1]1

Participants

6

Reactant 4

HCID 712FormaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 21226129Dichloromethane methanolHCID 59513880N-(3-{3-[2-(1,2,3,4-tetrahydro-7-isoquinolinylamino)-4-pyrimidinyl]-pyrazolo[1,5-a]pyridin-2-yl}phenyl)benzamide

Product 1

HCID 59513756N-[3-(3-{2-[(2-methyl-1,2,3,4-tetrahydro-7-isoquinolinyl)amino]-4-pyrimidinyl}pyrazolo[1,5-a]pyridin-2-yl)phenyl]benzamide

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

To a solution of N-(3-{3-[2-(1,2,3,4-tetrahydro-7-isoquinolinylamino)-4-pyrimidinyl]pyrazolo[1,5-a]pyridin-2-yl}phenyl)benzamide (107 mg, 0.199 mmol) in 2:1 DCM/MeOH (1.5 mL) was added 37% aq. formaldehyde (50 μL, 0.67 mmol), glacial acetic acid (13 μL) and sodium triacetoxyborohydride (64 mg, 0.30 mmol). The mixture was stirred at rt for 1 h. The mixture was worked up by removal of solvent with a totary evaporator and partitioning the residue between saturated aq. NaHCO3 and 5:1 CHCl3/isopropanol. The organic layer was separated, dried and concentrated to give 67 mg of crude material. Purification by silica gel chromatography (0 to 30% methanol in DCM) afforded 60.4 mg of the title compound as a cream-colored solid. LCMS (ES)+ 552.3. 1H NMR (400 MHz, DMSO-d6) δ 2.47 (s, 3H), 2.57 (bs, 2H), 2.72 (m, 2H), 3.39 (s, 2H), 6.49 (d, 1H, J=5.6), 6.95 (d, 1H, J=8.0, 7.10 (t, 1H, J=6.8), 7.28 (d, 1H, J=8.0), 7.37 (d, 1H, J=8.0), 7.42-7.56 (m, 5H), 7.93 (d, 2H, J=7.2), 8.11 (s, 1H), 8.22 (d, 1H, J=5.6), 8.45 (d, 1H, J=8.8), 8.81 (d, 1H, J=7.2, 9.41 (s, 1H), 10.37 (s, 1H).

Workup

  1. customThe mixture was worked up by removal of solvent with a totary evaporator
  2. custompartitioning the residue between saturated aq. NaHCO3 and 5:1 CHCl3/isopropanol
  3. customThe organic layer was separated
  4. customdried
  5. concentrationconcentrated
  6. customto give 67 mg of crude material
  7. customPurification by silica gel chromatography (0 to 30% methanol in DCM)

Sources & evidence

ORD record
ord-f6d4e34232ec485e9c39c7eeaa2c967d
Source dataset
uspto-grants-2010_10
Patent number
US07812022B2

Reaction notes

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