Hydrochloric Acid → N-{3-[3-(2-{[2-(Dimethylamino)-2,3-dihydro-1H-inden-5-yl]amino}pyrimidin-4-yl)pyrazolo[1,5-a]pyridin-2-yl]phenyl}-2-(2-thienyl)acetamide

HRID 1157620노트

반응식

HRID 1157620 반응식
O1C(C2C=C(N[C:13]3[N:18]=[C:17]([C:19]4[C:20]([C:28]5[CH:29]=[C:30]([NH:34][C:35](=[O:42])[CH2:36][C:37]6[S:38][CH:39]=[CH:40][CH:41]=6)[CH:31]=[CH:32][CH:33]=5)=[N:21][N:22]5[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=45)[CH:16]=[CH:15][N:14]=3)C=CC=2)=CN=C1.[NH2:43][C:44]1[CH:45]=[C:46]2[C:50](=[CH:51][CH:52]=1)[CH2:49][CH:48]([N:53]([CH3:55])[CH3:54])[CH2:47]2.Cl.C(OCC)C>CC(O)C>[CH3:54][N:53]([CH3:55])[CH:48]1[CH2:47][C:46]2[C:50](=[CH:51][CH:52]=[C:44]([NH:43][C:13]3[N:18]=[C:17]([C:19]4[C:20]([C:28]5[CH:29]=[C:30]([NH:34][C:35](=[O:42])[CH2:36][C:37]6[S:38][CH:39]=[CH:40][CH:41]=6)[CH:31]=[CH:32][CH:33]=5)=[N:21][N:22]5[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=45)[CH:16]=[CH:15][N:14]=3)[CH:45]=2)[CH2:49]1

참가 물질

6

반응물 4

HCID 313Hydrochloric AcidHCID 3283Diethyl EtherHCID 54309634HCID 54309634, 화합물HCID 57737194N-{3-[3-(2-{[3-(1,3-Oxazol-5-yl)phenyl]amino}-4-pyrimidinyl)pyrazolo[1,5-a]pyridin-2-yl]phenyl}-2-(2-thienyl)acetamide

생성물 1

HCID 16749910N-{3-[3-(2-{[2-(Dimethylamino)-2,3-dihydro-1H-inden-5-yl]amino}pyrimidin-4-yl)pyrazolo[1,5-a]pyridin-2-yl]phenyl}-2-(2-thienyl)acetamide

시약·촉매·용매 1

HCID 3776Isopropanol용매

반응 조건

온도
180 °C

실험 절차

The title compound was synthesized by combining N-{3-[3-(2-chloro-4-pyrimidinyl)pyrazolo[1,5-a]pyridin-2-yl]phenyl}-2-(2-thienyl)acetamide (147 mg, 0.33 mmol) (see Example 2, step B) and (5-amino-2,3-dihydro-1H-inden-2-yl)dimethylamine (70 mg, 0.40 mmol) in i-PrOH (2 mL) and adding 1M hydrochloric acid in diethyl ether (33 uL, 0.03 mmol). The reaction was heated to 180° C. in the microwave for 20 min. repeatedly until LC/MS analysis of the reaction mixture showed consumption of starting material. The reaction product was concentrated to a residue, partitioned between chloroform and saturated aqueous NaHCO3 and the organic fraction was washed with brine. The crude organic solution was dried with Na2SO4 and concentrated. The crude product was purified by silica gel flash column chromatography (DCM: 0-100% 90:9:1 DCM:MeOH:NH4OH(aq)). Purification yielded 43 mg (22%) of a brown powder. 1H NMR (400 MHz, DMSO-d6) δ 10.34 (s, 1H), 9.41 (s, 1H), 8.81 (d, J=6.9 Hz, 1H), 8.46 (m, 1H), 8.21 (dd, J=5.2, 4.1 Hz, 1H), 7.90-7.87 (m, 1H), 7.73 (d, J=8.0 Hz, 1H), 7.64 (d, J=15.4 Hz, 1H), 7.48-7.35 (m, 4H), 7.25 (d, J=7.7 Hz, 1H), 7.11 (t, J=7.0 Hz, 1H), 7.06-7.02 (m, 1H), 6.97-6.94 (m, 1H), 6.45 (dd, J=8.6, 5.4 Hz, 1H), 3.86 (s, 2H), 3.30 (s, 6H), 3.02-2.86 (m, 2H), 2.70-2.63 (m, 1H), 2.17 (s, 2H). ES-LC/MS m/z=586 [M+H]+.

후처리

  1. customconsumption of starting material
  2. concentrationThe reaction product was concentrated to a residue
  3. custompartitioned between chloroform and saturated aqueous NaHCO3
  4. washthe organic fraction was washed with brine
  5. dry with materialThe crude organic solution was dried with Na2SO4
  6. concentrationconcentrated
  7. customThe crude product was purified by silica gel flash column chromatography (DCM: 0-100% 90:9:1 DCM:MeOH:NH4OH(aq))
  8. customPurification

출처 및 근거

ORD 기록
ord-65cd407dc9b047208f9adb907ea55c0f
출처 데이터셋
uspto-grants-2010_10
특허 번호
US07807673B2

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