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 1091687ノート

反応式

HRID 1091687 の反応式
[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

参加物

7

反応物 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

生成物 1

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

試薬・触媒・溶媒 2

HCID 6344Dichloromethane触媒HCID 6344Dichloromethane溶媒

実験手順

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%).

後処理

  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

出典と根拠

ORDレコード
ord-ad0a227bb96741c293e5ba08a4734cae
出典データセット
uspto-grants-2012_03
特許番号
US08129397B2

反応ノート

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