Acetic Acid → 6-Methyl-2-((4-((thiazol-2-ylmethylamino)methyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)methyl)thieno[2,3-d]pyrimidin-4(3H)-one

HRID 1091687Notes

Reaction equation

HRID 1091687 reaction equation
[CH3:1][C:2]1[S:23][C:5]2[N:6]=[C:7]([CH2:11][N:12]3[CH:16]=[C:15]([CH:17]=O)[C:14]([C:19]([F:22])([F:21])[F:20])=[N:13]3)[NH:8][C:9](=[O:10])[C:4]=2[CH:3]=1.[S:24]1[CH:28]=[CH:27][N:26]=[C:25]1[CH2:29][NH2:30].C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl>[CH3:1][C:2]1[S:23][C:5]2[N:6]=[C:7]([CH2:11][N:12]3[CH:16]=[C:15]([CH2:17][NH:30][CH2:29][C:25]4[S:24][CH:28]=[CH:27][N:26]=4)[C:14]([C:19]([F:22])([F:21])[F:20])=[N:13]3)[NH:8][C:9](=[O:10])[C:4]=2[CH:3]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 27565071,3-Thiazol-2-ylmethanamineHCID 5049666Sodium triacetoxyborohydrideHCID 866303971-((6-Methyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidin-2-yl)methyl)-3-(trifluoromethyl)-1H-pyrazole-4-carbaldehyde

Product 1

HCID 425969796-Methyl-2-((4-((thiazol-2-ylmethylamino)methyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)methyl)thieno[2,3-d]pyrimidin-4(3H)-oneYield 24.1%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneCatalystHCID 6344DichloromethaneSolvent

Procedure

A mixture of 1-((6-methyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidin-2-yl)methyl)-3-(trifluoromethyl)-1H-pyrazole-4-carbaldehyde (0.55 g, 1.62 mmol) and thiazol-2-ylmethanamine (925 mg, 8.10 mmol) in DCM (11 mL) was acidified to pH 5 with acetic acid (1 mL) before the addition of sodium triacetoxyborohydride (1.72 g, 8.10 mmol). The resultant mixture was stirred at RT overnight. The reaction mixture was quenched with MeOH, passed through an SCX column and eluted with 2M NH3 in MeOH. The sample was concentrated in vacuo. Purification by flash column chromatography-silica gel and elution with 3-5% MeOH:DCM (3 drops of DIPEA per litre), followed by a second flash column and elution with 3-4% MeOH:DCM (3 drops of DIPEA per litre) gave the title product as a white solid (172 mg, 0.391 mmol, 24%).

Workup

  1. customThe reaction mixture was quenched with MeOH
  2. washeluted with 2M NH3 in MeOH
  3. concentrationThe sample was concentrated in vacuo
  4. customPurification
  5. washby flash column chromatography-silica gel and elution with 3-5% MeOH
  6. washDCM (3 drops of DIPEA per litre), followed by a second flash column and elution with 3-4% MeOH

Sources & evidence

ORD record
ord-ad0a227bb96741c293e5ba08a4734cae
Source dataset
uspto-grants-2012_03
Patent number
US08129397B2

Reaction notes

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