Triethylsilane → 1-((R)-4-methyl-1,3,4,5-tetrahydropyrazolo[3,4,5-de][1,6]naphthyridin-7-yl)-3-((R)-1-phenylethyl)urea

HRID 590844ノート

反応式

HRID 590844 の反応式
COC1C=CC(C[N:8]2[CH:17]([CH3:18])[CH2:16][C:15]3[N:14]=[C:13]([NH:19][C:20]([NH:22][C@@H:23]([C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)[CH3:24])=[O:21])[CH:12]=[C:11]4[NH:31][N:32]=[C:9]2[C:10]=34)=CC=1.C([SiH](CC)CC)C>C(O)(C(F)(F)F)=O>[CH3:18][C@@H:17]1[CH2:16][C:15]2[N:14]=[C:13]([NH:19][C:20]([NH:22][C@@H:23]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[CH3:24])=[O:21])[CH:12]=[C:11]3[NH:31][N:32]=[C:9]([C:10]=23)[NH:8]1

参加物

4

反応物 2

HCID 12052TriethylsilaneHCID 1182719941-(3-(4-methoxybenzyl)-4-methyl-1,3,4,5-tetrahydropyrazolo[3,4,5-de][1,6]naphthyridin-7-yl)-3-((R)-1-phenylethyl)urea

生成物 1

HCID 1362369311-((R)-4-methyl-1,3,4,5-tetrahydropyrazolo[3,4,5-de][1,6]naphthyridin-7-yl)-3-((R)-1-phenylethyl)urea

試薬・触媒・溶媒 1

HCID 6422Trifluoroacetic acid溶媒

実験手順

1-(3-(4-methoxybenzyl)-4-methyl-1,3,4,5-tetrahydropyrazolo[3,4,5-de][1,6]naphthyridin-7-yl)-3-((R)-1-phenylethyl)urea (100 mg, 0.143 mmol) was taken in TFA (0.7 mL) and stirred at room temperature for 30 minutes. Triethylsilane (91 uL, 0.572 mmol) was added to the reaction mixture and stirred for 15 minutes at room temperature then heated at 80° C. for 30 minutes. The reaction mixture was concentrated, taken in DCM and washed with aqueous sodium bicarbonate, brine, dried with sodium sulfate and concentrated. Purification of the residue by flash column (0-15% MeOH-DCM) followed by SFC separation with a Chiralpak AS-H column gave 1-((R)-4-methyl-1,3,4,5-tetrahydropyrazolo[3,4,5-de][1,6]naphthyridin-7-yl)-3-((R)-1-phenylethyl)urea as peak 1. MS ESI calc'd. for C18H20N6O [M+H]+ 337. found 337. 1H NMR (ppm, 500 MHz, DMSO-d6) δ 11.29 (s, 1H), 8.90 (s, 1H), 8.40 (br, s, 1H), 7.32 (dd, J=3.4, 7.9, 4H), 7.24-7.14 (m, 1H), 7.00 (s, 1H), 6.30 (s, 1H), 4.83 (m, 1H), 3.65 (m, 1H), 2.88-2.77 (m, 1H), 2.67-2.53 (m, 1H), 1.39 (d, J=6.9, 3H), 1.29 (d, J=6.3, 3H).

後処理

  1. stirringstirred for 15 minutes at room temperature
  2. temperaturethen heated at 80° C. for 30 minutes
  3. concentrationThe reaction mixture was concentrated
  4. washwashed with aqueous sodium bicarbonate, brine
  5. dry with materialdried with sodium sulfate
  6. concentrationconcentrated
  7. customPurification of the residue by flash column (0-15% MeOH-DCM)
  8. customfollowed by SFC separation with a Chiralpak AS-H column

出典と根拠

ORDレコード
ord-a1671c2c2e5d457b8495ae482e5a3a70
出典データセット
uspto-grants-2016_01
特許番号
US09233979B2

反応ノート

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