Acetaldehyde → 2-(1-ethyl-4-(4-(7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)piperidin-4-yl)acetonitrile

HRID 1852985ノート

反応式

HRID 1852985 の反応式
Cl.[CH3:2][N:3]1[CH:7]=[C:6]([C:8]2[N:13]=[C:12]([C:14]3[CH:15]=[N:16][N:17]([C:19]4([CH2:25][C:26]#[N:27])[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]4)[CH:18]=3)[N:11]3[CH:28]=[CH:29][N:30]=[C:10]3[CH:9]=2)[CH:5]=[N:4]1.[C:31](#N)[CH3:32].C(N(CC)CC)C.C(=O)C.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C(=O)(O)[O-].CCOC(C)=O>[CH2:31]([N:22]1[CH2:21][CH2:20][C:19]([CH2:25][C:26]#[N:27])([N:17]2[CH:18]=[C:14]([C:12]3[N:11]4[CH:28]=[CH:29][N:30]=[C:10]4[CH:9]=[C:8]([C:6]4[CH:5]=[N:4][N:3]([CH3:2])[CH:7]=4)[N:13]=3)[CH:15]=[N:16]2)[CH2:24][CH2:23]1)[CH3:32]

参加物

8

反応物 5

HCID 177AcetaldehydeHCID 6342AcetonitrileHCID 8471TriethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 67456826HCID 67456826、化合物

生成物 1

HCID 866853092-(1-ethyl-4-(4-(7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)piperidin-4-yl)acetonitrile収率 26.2%

試薬・触媒・溶媒 2

HCID 769Bicarbonate Ion溶媒HCID 8857Ethyl Acetate溶媒

実験手順

2-(4-(4-(7-(1-Methyl-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)piperidin-4-yl)acetonitrile hydrochloride (Example 28, Step A; 27.0 mg, 0.0543 mmol) was suspended in acetonitrile (543 μL, 0.0543 mmol). To this was added triethylamine (30.3 μL, 0.217 mmol) to freebase, followed by acetaldehyde (30.5 μL, 0.543 mmol). After 30 minutes, NaBH(OAc)3 (57.6 mg, 0.272 mmol) was added to reduce. After stirring for 30 minutes, the reaction mixture was diluted in saturated bicarbonate and EtOAc. The aqueous layer was back-extracted with DCM. The combined organic layer was washed with brine, dried with MgSO4, filtered and concentrated. Purification of the resulting crude material by reverse phase HPLC using a 0-100% acetonitrile/water gradient afforded afford 2-(1-ethyl-4-(4-(7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)piperidin-4-yl)acetonitrile (5.9 mg, 26% yield). MS (apci) m/z=416.2 (M+H).

後処理

  1. extractionThe aqueous layer was back-extracted with DCM
  2. washThe combined organic layer was washed with brine
  3. dry with materialdried with MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification of the resulting crude material by reverse phase HPLC
  7. customgradient afforded

出典と根拠

ORDレコード
ord-411a28a4cf764084be8944435b3f94b6
出典データセット
uspto-grants-2015_02
特許番号
US08962596B2

反応ノート

読み込み中…