3-Methoxybenzaldehyde → HCID 25117486, compound

HRID 2189150Notes

Reaction equation

HRID 2189150 reaction equation
[NH2:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11]3[CH:16]=[C:15]([C:17]4[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=4[O:23][CH2:24][CH:25]([CH3:27])[CH3:26])[NH:14][C:13](=[O:28])[N:12]=3)[CH:9]=2)[NH:4][N:3]=1.[CH:29](=O)[C:30]1[CH:35]=[CH:34][CH:33]=[C:32]([O:36][CH3:37])[CH:31]=1.C([BH3-])#N.[Na+]>C(O)(=O)C.CN(C)C=O>[CH3:37][O:36][C:32]1[CH:31]=[C:30]([CH2:29][NH:1][C:2]2[C:10]3[C:5](=[CH:6][CH:7]=[C:8]([C:11]4[CH:16]=[C:15]([C:17]5[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=5[O:23][CH2:24][CH:25]([CH3:26])[CH3:27])[NH:14][C:13](=[O:28])[N:12]=4)[CH:9]=3)[NH:4][N:3]=2)[CH:35]=[CH:34][CH:33]=1

Participants

6

Reactant 3

HCID 115693-MethoxybenzaldehydeHCID 5003444Sodium cyanoborohydrideHCID 251213724-(3-amino-1H-indazol-5-yl)-6-(2-isobutoxyphenyl)pyrimidin-2(1H)-one

Product 1

HCID 25117486HCID 25117486, compoundYield 98%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

To a 50 mL round bottom flask were added commercially available 4-(3-amino-1H-indazol-5-yl)-6-(2-isobutoxyphenyl)pyrimidin-2(1H)-one (130 mg, 0.35 mmol), m-anisaldehyde (420 μL, 3.5 mmol, 10 eq), dimethylformamide (10 mL) and glacial acetic acid (10 drops). The reaction mixture was heated to 50° C. in an oil bath and stirred for 1 h. The mixture was allowed to cool before adding sodium cyanoborohydride (1M THF solution (Aldrich), 3 mL, 3 mmol) and subsequently stirred at room temperature for 1 h. Formation of product was confirmed by LC/MS and was purified by preparatory HPLC (reverse-phase, acetonitrile/water with 0.1% formic acid) to yield 40 mg (98%) of the title compound: 1H-NMR (400 MHz, d6-DMSO): δ 11.78 (s, 1H), 11.64 (s, 1H), 8.73 (s, 1H), 8.06 (d, 1H), 7.60 (d, 1H), 7.46-7.54 (m, 1H), 7.28-7.34 (m, 1H), 7.15-7.26 (m, 2H), 7.06-7.12 (m, 1H), 6.96-7.01 (m, 1H), 6.73-6.81 (m, 1H), 4.42-4.48 (m, 2H), 3.82-3.88 (m, 2H), 3.72 (s, 3H), 1.94-2.07 (m, 1H), 0.90-0.95 (m, 6H). MS (EI) for C29H29N5O3: 495 (MH+).

Workup

  1. temperatureto cool
  2. stirringsubsequently stirred at room temperature for 1 h
  3. customwas purified by preparatory HPLC (reverse-phase, acetonitrile/water with 0.1% formic acid)

Sources & evidence

ORD record
ord-24df561a237d4c6f85ed31725993469e
Source dataset
uspto-grants-2012_12
Patent number
US08324231B2

Reaction notes

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