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

HRID 1049925노트

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HRID 1049925 반응식
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

참가 물질

5

반응물 3

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

생성물 1

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

시약·촉매·용매 1

HCID 31374Dimethylacetamide용매

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온도
100 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-8b03d9613a6f44029575e246f93cb55e
출처 데이터셋
uspto-grants-2016_07
특허 번호
US09382241B2

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