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Sodium Acetate → 1,3-dimethyl-1H-pyrazole-4-carboxylic acid {4-[3-cyclopropylmethyl-1-(2-fluoro-benzyl)-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-ylmethyl]-phenyl}-methyl-amide

HRID 720671
Notes
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Reaction equation

HRID 720671 reaction equation
[CH:1]1([CH2:4][N:5]2[C:13]3[N:12]=[C:11]([CH2:14][C:15]4[CH:20]=[CH:19][C:18]([N:21]([CH3:32])[C:22]([C:24]5[C:25]([CH3:31])=[N:26][N:27]([CH3:30])[C:28]=5Cl)=[O:23])=[CH:17][CH:16]=4)[NH:10][C:9]=3[C:8](=[O:33])[N:7]([CH2:34][C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=3[F:41])[C:6]2=[O:42])[CH2:3][CH2:2]1.C([O-])(=O)C.[Na+]>[Pd].ClCCl.CO>[CH:1]1([CH2:4][N:5]2[C:13]3[N:12]=[C:11]([CH2:14][C:15]4[CH:16]=[CH:17][C:18]([N:21]([CH3:32])[C:22]([C:24]5[C:25]([CH3:31])=[N:26][N:27]([CH3:30])[CH:28]=5)=[O:23])=[CH:19][CH:20]=4)[NH:10][C:9]=3[C:8](=[O:33])[N:7]([CH2:34][C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=3[F:41])[C:6]2=[O:42])[CH2:2][CH2:3]1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 2

HCID 517045Sodium AcetateHCID 865908345-chloro-1,3-dimethyl-1H-pyrazole-4-carboxylic acid {4-[3-cyclopropylmethyl-1-(2-fluoro-benzyl)-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-ylmethyl]-phenyl}-methyl-amide

Product 1

HCID 865908371,3-dimethyl-1H-pyrazole-4-carboxylic acid {4-[3-cyclopropylmethyl-1-(2-fluoro-benzyl)-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-ylmethyl]-phenyl}-methyl-amideYield 9.1%

Reagents, catalysts & solvents 3

HCID 23938
Palladium
Catalyst
HCID 887MethanolSolvent
HCID 6344DichloromethaneSolvent

Procedure

A mixture of 5-chloro-1,3-dimethyl-1H-pyrazole-4-carboxylic acid {4-[3-cyclopropylmethyl-1-(2-fluoro-benzyl)-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-ylmethyl]-phenyl}-methyl-amide (81.5 mg, 0.14 mmol) (prepared as described in example 104), 10% palladium on carbon (313 mg), and sodium acetate (28.3 mg, 0.35 mmol) in dichloromethane (25 mL) and methanol (25 mL) was hydrogenated at 50 psi on a Parr apparatus for 8 days. At this time, the reaction was filtered through a pad of celite and washed with a 90/10 dichloromethane/methanol solution (100 mL). The filtrated was concentrated in vacuo. The resulting residue was purified by HPLC (15–60% acetonitrile/water (0.075% trifluoroacetic acid in both solvents) over 40 min). Fractions with the desired product were combined and concentrated in vacuo. The resulting residue was diluted with dichloromethane (100 mL) and was washed with a saturated aqueous sodium bicarbonate solution (25 mL). The organics were dried over magnesium sulfate, filtered, and concentrated in vacuo. The resulting solid was dried in vacuo for 24 h to afford 1,3-dimethyl-1H-pyrazole-4-carboxylic acid {4-[3-cyclopropylmethyl-1-(2-fluoro-benzyl)-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-ylmethyl]-phenyl}-methyl-amide (7.0 mg, 9.1%) as a white solid: 1H NMR (DMSO-d6, 300 MHz) δ13.122 (broad s, 1H), 6.79 (m, 9H), 6.33 (s, 1H), 4.76 (s, 2H), 3.70 (s, 2H), 3.47 (d, J=6.96 Hz, 2H), 3.11 (s, 3H), 2.87 (s, 3H), 1.75 (s, 3H), 0.85 (broad s, 1H), 0.026 (m, 4H).

Workup

  1. filtrationAt this time, the reaction was filtered through a pad of celite
  2. washwashed with a 90/10 dichloromethane/methanol solution (100 mL)
  3. concentrationThe filtrated was concentrated in vacuo
  4. customThe resulting residue was purified by HPLC (15–60% acetonitrile/water (0.075% trifluoroacetic acid in both solvents) over 40 min)
  5. concentrationconcentrated in vacuo
  6. additionThe resulting residue was diluted with dichloromethane (100 mL)
  7. washwas washed with a saturated aqueous sodium bicarbonate solution (25 mL)
  8. dry with materialThe organics were dried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe resulting solid was dried in vacuo for 24 h

Sources & evidence

ORD record
ord-2f36da726b3e4309ada6f807deb3d0f0
Source dataset
uspto-grants-2006_11
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07135475B2

Reaction notes

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