Trifluoroacetic acid → HCID 178440683, 화합물

HRID 2040694노트

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HRID 2040694 반응식
FC(F)(F)C(O)=O.[C:8]([C:12]1[CH:63]=[CH:62][C:15]2[NH:16][C:17]([CH2:19][CH2:20][CH:21]3[CH2:24][CH:23]([N:25]([CH2:30][C@@H:31]4[C@H:35]5[O:36]C(C)(C)[O:38][C@H:34]5[C@H:33]([N:41]5[C:45]6[N:46]=[CH:47][N:48]=[C:49]([NH:50]CC7C=CC(OC)=CC=7OC)[C:44]=6[CH:43]=[CH:42]5)[CH2:32]4)[CH2:26][CH:27]4[CH2:29][CH2:28]4)[CH2:22]3)=[N:18][C:14]=2[CH:13]=1)([CH3:11])([CH3:10])[CH3:9].C([SiH](CC)CC)C.C([O-])([O-])=O.[K+].[K+]>CO.O>[NH2:50][C:49]1[C:44]2[CH:43]=[CH:42][N:41]([C@@H:33]3[CH2:32][C@H:31]([CH2:30][N:25]([CH:23]4[CH2:22][CH:21]([CH2:20][CH2:19][C:17]5[NH:16][C:15]6[CH:62]=[CH:63][C:12]([C:8]([CH3:9])([CH3:10])[CH3:11])=[CH:13][C:14]=6[N:18]=5)[CH2:24]4)[CH2:26][CH:27]4[CH2:29][CH2:28]4)[C@@H:35]([OH:36])[C@H:34]3[OH:38])[C:45]=2[N:46]=[CH:47][N:48]=1

참가 물질

8

반응물 4

HCID 6422Trifluoroacetic acidHCID 11430Potassium CarbonateHCID 12052TriethylsilaneHCID 178491007HCID 178491007, 화합물

생성물 1

HCID 178440683HCID 178440683, 화합물수율 50.4%

시약·촉매·용매 3

HCID 962Water촉매HCID 887Methanol용매HCID 962Water용매

실험 절차

Trifluoroacetic Acid (10 mL) added to a mixture of Water (1 mL) and 7-((3aS,4R,6R,6aR)-6-(((3-(2-(5-(tert-butyl)-1H-benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(cyclopropylmethyl)amino)methyl)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)-N-(2,4-dimethoxybenzyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine (0.52 g, 0.68 mmol) at RT. The reaction was stirred overnight at RT and Triethylsilane (0.22 mL. 1.4 mmol) was added. The volatiles were removed in vacuo and resulting residue was taken up in MeOH (15 mls), 500 mgs of K2CO3 and 8 drops H2O were added and the reaction stirred at RT for 1 hour. The mixture was filtered and the filter cake washed with 10 ml MeOH. The filtrate was concentrated and the resulting residue purified by flash chromatography (DCM/7N NH3 in MeOH 90:10) to give the desired product (0.196 g) as an off white foam. MS (ESI+) for C33H45N7O2 m/z 572.6 [M+H]+; MS (ESP) for C33H45N7O2 m/z 570.3 [M−H]−; HPLC purity >90% (ret. time, 2.850 min.) 1H NMR (400 MHz, d4-MeOH) δH 7.944 (s, 1H), 7.361 (s, 1H), 7.280-7.259 (m, 1H), 7.172-7.150 (m, 1H), 7.092-7.078 (m, 1H), 6.484-6.475 (d, J=3.6 Hz, 1H), 4.222-4.185 (m, 1H), 3.815-3.779 (m, 1H), 3.329 (m, 0.5H (methine of trans isomer)), 2.961 (m, 0.5H (methine of cis isomer), 2.745-2.627 (m, 3H), 2.503-2.450 (m, 1H), 2.301-2.187 (m, 5H), 2.036-1.890 (m, 2H), 1.793-1.776 (m, 3H), 1.529-1.385 (m, 2H), 1.246 (s, 9H), 0.808-0.739 (m, 1H), 0.394-0.362 (m, 2H), 0.012-0.013 (m, 2H). Retention time: 2.850 minutes. HPLC Conditions:Agilent Zorbax Exlipse XDB-C18 column, 4.6×50 mm (1.8 urn packing), Solvent A—Water (0.1% TFA), Solvent B—Acetonitrile (0.07% TFA) 6 min gradient from 5 to 95% B; 1 min hold; then recycle.

후처리

  1. customThe volatiles were removed in vacuo
  2. customresulting residue
  3. stirringthe reaction stirred at RT for 1 hour
  4. filtrationThe mixture was filtered
  5. washthe filter cake washed with 10 ml MeOH
  6. concentrationThe filtrate was concentrated
  7. customthe resulting residue purified by flash chromatography (DCM/7N NH3 in MeOH 90:10)

출처 및 근거

ORD 기록
ord-aec54301b4f34ae0821a6513c73881bf
출처 데이터셋
uspto-grants-2013_11
특허 번호
US08580762B2

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