1-methyl-1H-imidazole-5-carbaldehyde → 6,6-Dimethyl-2-(6-{[(1-methyl-1h-imidazol-5-yl)methyl]amino}-2,3-dihydro-4h-1,4-benzoxazin-4-yl)-6,7-dihydro[1,3]thiazolo[5,4-c]pyridin-4(5h)-one

HRID 885969Notes

Reaction equation

HRID 885969 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]2[O:10][CH2:9][CH2:8][N:7]([C:11]3[S:12][C:13]4[C:14](=[O:22])[NH:15][C:16]([CH3:21])([CH3:20])[CH2:17][C:18]=4[N:19]=3)[C:6]=2[CH:23]=1.[CH3:24][N:25]1[C:29]([CH:30]=O)=[CH:28][N:27]=[CH:26]1.C([BH3-])#N.[Na+]>CC(O)=O.CO>[CH3:20][C:16]1([CH3:21])[NH:15][C:14](=[O:22])[C:13]2[S:12][C:11]([N:7]3[C:6]4[CH:23]=[C:2]([NH:1][CH2:30][C:29]5[N:25]([CH3:24])[CH:26]=[N:27][CH:28]=5)[CH:3]=[CH:4][C:5]=4[O:10][CH2:9][CH2:8]3)=[N:19][C:18]=2[CH2:17]1

Participants

6

Reactant 3

HCID 5735921-methyl-1H-imidazole-5-carbaldehydeHCID 5003444Sodium cyanoborohydrideHCID 58441690HCID 58441690, compound

Product 1

HCID 671894116,6-Dimethyl-2-(6-{[(1-methyl-1h-imidazol-5-yl)methyl]amino}-2,3-dihydro-4h-1,4-benzoxazin-4-yl)-6,7-dihydro[1,3]thiazolo[5,4-c]pyridin-4(5h)-oneYield 32%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 887MethanolSolvent

Procedure

To a stirred solution of Example 42 (0.03 g, 0.10 mmol) in 5% AcOH in MeOH (1 mL) was added 1-methyl-5-imidazolecarboxaldehyde (0.01 g, 0.14 mmol). The reaction mixture was stirred at r.t. for 20 minutes. Sodium cyanoborohydride (0.02 g, 0.39 mmol) was then added, and the reaction mixture stirred for a further 10 minutes before being concentrated in vacuo. Purification by preparative HPLC (Method 6) gave the title compound (0.01 g, 32%) as a yellow oil. δH (CDCl3) 8.28 (1H, s), 8.17 (1H, s), 7.22 (1H, s), 7.17 (1H, d, J 2.6 Hz), 6.82 (1H, d, J 8.7 Hz), 6.47 (1H, dd, J 8.9 and 2.8 Hz), 5.82 (1H, s), 4.34 (2H, s), 4.29-4.22 (2H, m), 4.19-4.11 (2H, m), 3.86 (3H, s), 2.86 (2H, s), 1.39 (6H, s). LCMS (ES+) 425.42 (M+H)+, RT 1.85 minutes (Method 1).

Workup

  1. stirringthe reaction mixture stirred for a further 10 minutes
  2. concentrationbefore being concentrated in vacuo
  3. customPurification by preparative HPLC (Method 6)

Sources & evidence

ORD record
ord-80bdbd72a58a4b29a1367df6caf51ff6
Source dataset
uspto-grants-2012_08
Patent number
US08242116B2

Reaction notes

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