Triethylamine → tert-butyl N-[(3S)-1-(4-aminopyrido[3,2-d]pyrimidin-6-yl)-3-piperidyl]carbamate

HRID 1049925ノート

反応式

HRID 1049925 の反応式
Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]=[CH:7][N:8]=[C:9]([NH2:12])[C:10]=2[N:11]=1.[NH:13]1[CH2:18][CH2:17][CH2:16][C@H:15]([NH:19][C:20](=[O:26])[O:21][C:22]([CH3:25])([CH3:24])[CH3:23])[CH2:14]1.C(N(CC)CC)C>CC(N(C)C)=O>[NH2:12][C:9]1[C:10]2[N:11]=[C:2]([N:13]3[CH2:18][CH2:17][CH2:16][C@H:15]([NH:19][C:20](=[O:26])[O:21][C:22]([CH3:24])([CH3:23])[CH3:25])[CH2:14]3)[CH:3]=[CH:4][C:5]=2[N:6]=[CH:7][N:8]=1

参加物

5

反応物 3

HCID 8471TriethylamineHCID 1514171tert-butyl N-[(3S)-piperidin-3-yl]carbamateHCID 867038966-Chloropyrido[3,2-d]pyrimidin-4-amine

生成物 1

HCID 86703922tert-butyl N-[(3S)-1-(4-aminopyrido[3,2-d]pyrimidin-6-yl)-3-piperidyl]carbamate収率 66.2%

試薬・触媒・溶媒 1

HCID 31374Dimethylacetamide溶媒

反応条件

温度
100 °C

実験手順

To 40 mL screw-cap vials was added 6-chloropyrido[3,2-d]pyrimidin-4-amine (2.00 g, 11.1 mmol) followed by tert-butyl N-[(3S)-3-piperidyl]carbamate (1.1 equiv., 12.2 mmol, 2.44 g) then dimethylacetamide (10 mL) and triethylamine (3 equiv., 33.2 mmol, 4.65 mL). The reaction was capped and shaken at 100° C. for 42 h, then an additional 24 h at 115° C. The reaction was cooled to room temperature, then partitioned with ethyl acetate:water. Residual chloride starting material was removed by filtration. The filtrate phases were separated, and the organics dried over sodium sulfate, filtered and concentrated, yielding 2.53 g of product. 1H NMR (400 MHz, DMSO) δ 8.19-8.13 (s, 1H), 7.81-7.74 (d, J=9.3 Hz, 1H), 7.43-7.39 (d, J=9.1 Hz, 1H), 6.95-6.85 (d, J=6.6 Hz, 1H), 4.32-4.19 (m, 2H), 3.50-3.38 (m, 1H), 3.19-3.04 (m, 1H), 2.96-2.85 (m, 1H), 1.90-1.80 (m, 1H), 1.80-1.67 (m, 1H), 1.60-1.34 (m, 11H). LCMS M/Z (M+H)=345.

後処理

  1. customTo 40 mL screw-cap vials
  2. customThe reaction was capped
  3. customan additional 24 h
  4. customat 115° C
  5. temperatureThe reaction was cooled to room temperature
  6. custompartitioned with ethyl acetate
  7. customResidual chloride starting material was removed by filtration
  8. customThe filtrate phases were separated
  9. dry with materialthe organics dried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated

出典と根拠

ORDレコード
ord-8b03d9613a6f44029575e246f93cb55e
出典データセット
uspto-grants-2016_07
特許番号
US09382241B2

反応ノート

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