(1-Ethoxycyclopropoxy)trimethylsilane → 2-(1-Cyclopropyl-3-(4-(7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)azetidin-3-yl)acetonitrile

HRID 1853015ノート

反応式

HRID 1853015 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([CH2:23][C:24]#[N:25])[CH2:22][NH:21][CH2:20]4)[CH:18]=3)[N:11]3[CH:26]=[CH:27][N:28]=[C:10]3[CH:9]=2)[CH:5]=[N:4]1.C(O[C:32]1(O[Si](C)(C)C)[CH2:34][CH2:33]1)C.C([BH3-])#N.[Na+]>CO.C(O)(=O)C>[CH:32]1([N:21]2[CH2:22][C:19]([CH2:23][C:24]#[N:25])([N:17]3[CH:18]=[C:14]([C:12]4[N:11]5[CH:26]=[CH:27][N:28]=[C:10]5[CH:9]=[C:8]([C:6]5[CH:5]=[N:4][N:3]([CH3:2])[CH:7]=5)[N:13]=4)[CH:15]=[N:16]3)[CH2:20]2)[CH2:34][CH2:33]1

参加物

5

反応物 3

HCID 2734686(1-Ethoxycyclopropoxy)trimethylsilaneHCID 5003444Sodium cyanoborohydrideHCID 674570102-(3-(4-(7-(1-Methyl-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)azetidin-3-yl)acetonitrile hydrochloride

生成物 1

HCID 866853152-(1-Cyclopropyl-3-(4-(7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)azetidin-3-yl)acetonitrile収率 82%

試薬・触媒・溶媒 1

HCID 10129899Acetic acid methanol溶媒

実験手順

To a fine suspension of 2-(3-(4-(7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)azetidin-3-yl)acetonitrile hydrochloride (Example 62, 50.2 mg, 0.107 mmol) in 2:1 MeOH/acetic acid (0.60 mL) was added (1-ethoxycyclopropoxy)trimethylsilane (94.2 mg, 0.535 mmol) and the mixture was stirred at ambient temperature for 5 minutes. Sodium cyanoborohydride (42.5 mg, 0.642 mmol) was added in one portion and the mixture was stirred at 50° C. for 3 hours. The mixture was cooled to ambient temperature and concentrated to dryness. The residual white solid was partitioned into DCM and 1M K2CO3 (3 mL each) and the mixture was stirred until both layers were homogeneous. The DCM layer was removed and the aqueous layer was extracted with DCM. The combined DCM extracts were dried over Na2SO4, filtered through a Celite pad and concentrated to give a colorless glass. The glass was purified on a silica gel column eluting with a step gradient of EtOAc, 5% MeOH/EtOAc, and 10% MeOH/EtOAc to furnish the title compound (35 mg, 82% yield) as a white solid. MS (apci) m/z=400.2 (M+H).

後処理

  1. stirringthe mixture was stirred at 50° C. for 3 hours
  2. temperatureThe mixture was cooled to ambient temperature
  3. concentrationconcentrated to dryness
  4. customThe residual white solid was partitioned into DCM and 1M K2CO3 (3 mL each)
  5. stirringthe mixture was stirred until both layers
  6. customThe DCM layer was removed
  7. extractionthe aqueous layer was extracted with DCM
  8. dry with materialThe combined DCM extracts were dried over Na2SO4
  9. filtrationfiltered through a Celite pad
  10. concentrationconcentrated
  11. customto give a colorless glass
  12. customThe glass was purified on a silica gel column
  13. washeluting with a step gradient of EtOAc, 5% MeOH/EtOAc, and 10% MeOH/EtOAc

出典と根拠

ORDレコード
ord-bdaa869f7f0844cfb6b64ac3563ef914
出典データセット
uspto-grants-2015_02
特許番号
US08962596B2

反応ノート

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