Dichloromethane → HCID 58406334, compound

HRID 1910909Notes

Reaction equation

HRID 1910909 reaction equation
[Si]([O:8][CH2:9][C:10]1[N:14]2[CH2:15][C:16]3([C:31]4[CH:36]=[CH:35][C:34]([Cl:37])=[CH:33][CH:32]=4)[N:22]([C:23]([C:25]4[C:26]([CH3:30])=[N:27][O:28][CH:29]=4)=[O:24])[CH2:21][CH2:20][N:17]3[C:18](=[O:19])[C:13]2=[CH:12][CH:11]=1)(C(C)(C)C)(C)C.C(Cl)Cl>C(O)(=O)C.C1COCC1.O>[Cl:37][C:34]1[CH:33]=[CH:32][C:31]([C:16]23[N:22]([C:23]([C:25]4[C:26]([CH3:30])=[N:27][O:28][CH:29]=4)=[O:24])[CH2:21][CH2:20][N:17]2[C:18](=[O:19])[C:13]2[N:14]([C:10]([CH2:9][OH:8])=[CH:11][CH:12]=2)[CH2:15]3)=[CH:36][CH:35]=1

Participants

4

Reactant 2

HCID 6344DichloromethaneHCID 67369218HCID 67369218, compound

Product 1

HCID 58406334HCID 58406334, compoundYield 55.2%

Reagents, catalysts & solvents 1

HCID 21877175AcOH THF waterSolvent

Procedure

8-({[tert-butyl(dimethyl)silyl]oxy}methyl)-10a-(4-chlorophenyl)-1-[(3-methyl-1,2-oxazol-4-yl)carbonyl]-2,3,10,10a-tetrahydro-1H,5H-imidazo[1,2-a]pyrrolo[1,2-d]pyrazin-5-one (75 mg, 0.14 mmol) was dissolved in a mixture acetic acid/THF/water (3:1:1, 2.5 mL). The solution was stirred at room temperature overnight. After this time there was not anymore starting material (monitored by LCMS). CH2Cl2 was added (20 mL) and washed with saturated aqueous solution of NaHCO3 (3×7 mL). The organic layers were dried (MgSO4), filtered and the filtrate concentrated in vacuo to yield a colourless gum. Purification by flash column chromatography (Biotage SP4, 4 g cartridge, 0-10% MeOH gradient in CH2Cl2) gave 10a-(4-chlorophenyl)-8-(hydroxymethyl)-1-[(3-methyl-1,2-oxazol-4-yl)carbonyl]-2,3,10,10a-tetrahydro-1H,5H-imidazo[1,2-a]pyrrolo[1,2-d]pyrazin-5-one as a white solid (33 mg, 55% yield). 1H NMR (400 MHz, d6-acetone): δ 2.32 (d, 3H, J 0.5 Hz), 3.75-3.85 (m, 1H), 4.19-4.36 (m, 3H), 4.43-4.47 (d, 1H, J 13.1 Hz), 4.58-4.69 (m, 2H), 6.03 (d, 1H, J 13.2 Hz), 6.09 (d, 1H, J 3.8 Hz), 6.61 (d, 1H, J 3.8 Hz), 7.28-7.32 (m, 2H), 7.50-7.54 (m, 2H), 9.16 (s, 1H). ESI-MI m/z [M+H]+ 427.2.

Workup

  1. washwashed with saturated aqueous solution of NaHCO3 (3×7 mL)
  2. dry with materialThe organic layers were dried (MgSO4)
  3. filtrationfiltered
  4. concentrationthe filtrate concentrated in vacuo
  5. customto yield a colourless gum
  6. customPurification by flash column chromatography (Biotage SP4, 4 g cartridge, 0-10% MeOH gradient in CH2Cl2)

Sources & evidence

ORD record
ord-ecfc8a882e0542d595964cd30bc440c8
Source dataset
uspto-grants-2013_12
Patent number
US08604034B2

Reaction notes

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