Isopropanol → HCID 44816299、化合物

HRID 1697889ノート

反応式

HRID 1697889 の反応式
[CH2:1]([NH:3][C:4](=[O:34])[NH:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[N:13]=[C:14]([N:28]3[CH2:33][CH2:32][O:31][CH2:30][CH2:29]3)[C:15]3[CH2:20][N:19](C(OC(C)(C)C)=O)[CH2:18][C:16]=3[N:17]=2)=[CH:8][CH:7]=1)[CH3:2].C(O)(C(F)(F)F)=O.C(O)(C)C.C(=O)([O-])[O-]>ClCCl.C1(C)C=CC=CC=1>[CH2:1]([NH:3][C:4]([NH:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[N:13]=[C:14]([N:28]3[CH2:29][CH2:30][O:31][CH2:32][CH2:33]3)[C:15]3[CH2:20][NH:19][CH2:18][C:16]=3[N:17]=2)=[CH:8][CH:7]=1)=[O:34])[CH3:2]

参加物

7

反応物 4

HCID 3776IsopropanolHCID 6422Trifluoroacetic acidHCID 19660Carbonate IonHCID 46912801HCID 46912801、化合物

生成物 1

HCID 44816299HCID 44816299、化合物

試薬・触媒・溶媒 2

HCID 1140Toluene溶媒HCID 6344Dichloromethane溶媒

実験手順

Step 3—Synthesis of d: tert-butyl 2-(4-(3-ethylureido)phenyl)-4-morpholino-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate (c, 1.74 mmol) was dissolved in dichloromethane (5 mL), then TFA (3 mL) was added. The mixture was stirred at room temperature for 2 hours. Isopropanol and toluene were added and the resulting mixture was concentrated in vacuo. The resulting residue was azeotroped with toluene two more times. Methanol and methylene chloride (4 mL each) were added to the resulting residue, then PS-carbonate (2.5-3.5 mmol N/gram resin, 1.45 g) was added. The mixture was stirred at room temperature until the pH reached >7 (˜1 hr). The mixture was filtered, the resin was washed with methanol and dichloromethane. The filtrate was concentrated to provide 1-ethyl-3-(4-(4-morpholino-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)urea as a free amine, which was used in the next step. An aliquot was purified by reverse-phase HPLC to give the pure desired product: 1H NMR (400 MHz, DMSO) δ 9.57 (s, 1H), 8.75 (s, 1H), 8.19 (d, J=8.9, 2H), 7.50 (d, J=8.9, 2H), 6.38-6.08 (m, 1H), 4.71 (s, 2H), 4.38 (s, 2H), 3.72 (s, 8H), 3.24-3.03 (m, 2H), 1.06 (t, J=7.2, 3H); LC-MS: m/z=+369 (M+H)+.

後処理

  1. concentrationthe resulting mixture was concentrated in vacuo
  2. customThe resulting residue was azeotroped with toluene two more times
  3. additionMethanol and methylene chloride (4 mL each) were added to the resulting residue
  4. stirringThe mixture was stirred at room temperature until the pH
  5. custom>7 (˜1 hr)
  6. filtrationThe mixture was filtered
  7. washthe resin was washed with methanol and dichloromethane
  8. concentrationThe filtrate was concentrated

出典と根拠

ORDレコード
ord-3de7189012594c4cb5434f09ca7d12fe
出典データセット
uspto-grants-2012_04
特許番号
US08163763B2

反応ノート

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