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Chemical Structure| 1152311-90-4 Chemical Structure| 1152311-90-4

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Chemical Structure| 1152311-90-4

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Product Details of [ 1152311-90-4 ]

CAS No. :1152311-90-4
Formula : C29H31F3N2O6
M.W : 560.56
SMILES Code : C(NC=1C=C2C(=CC1F)N(C[C@@H]3COC(C)(C)O3)C(C(CO)(C)C)=C2)(=O)C4(CC4)C=5C=C6C(=CC5)OC(F)(F)O6
MDL No. :N/A

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Application In Synthesis of [ 1152311-90-4 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Upstream synthesis route of [ 1152311-90-4 ]

[ 1152311-90-4 ] Synthesis Path-Upstream   1~1

  • 1
  • [ 1152311-90-4 ]
  • [ 1152311-62-0 ]
YieldReaction ConditionsOperation in experiment
47%
Stage #1: With toluene-4-sulfonic acid In methanol; water at 80℃; for 0.75 h;
Stage #2: With sodium hydrogencarbonate In water; ethyl acetate
(R)-l-(2,2-difluorobenzo[d][l,3]dioxol-5-yl)-N-(l-((2,2-dimethyl-l,3-dioxolan-4- yl)methyl)-6-fluoro-2-(l-hydroxy-2-methylpropan-2-yl)-lH-indol-5- yl)cyclopropanecarboxamide (3.0 g, 5.4 mmol) was dissolved in methanol (52 mL). Water (5.2 mL) was added followed by p-TsOH.H2O (204 mg, 1.1 mmol). The reaction was heated at 80 °C for 45 minutes. The solution was concentrated and then partitioned between ethyl acetate and saturated NaHCO3 solution. The ethyl acetate layer was dried over MgSO4 and concentrated. The residue was purified by column chromatography (50-100 percent ethyl acetate - hexanes) to yield the product as a cream colored foamy solid. (1.3 g, 47 percent, ee >98percent by SFC). ESI-MS m/z calc. 520.5, found 521.7 (M+l)+. Retention time 1.69 minutes. 1H NMR (400 MHz, DMSO-rf6) δ 8.31 (s, IH), 7.53 (s, IH), 7.42 - 7.38 (m, 2H), 7.33 - 7.30 (m, 2H), 6.22 (s, IH), 5.01 (d, J = 5.2 Hz, IH), 4.90 (t, J = 5.5 Hz, IH), 4.75 (t, J = 5.8 Hz, IH), 4.40 (dd, J = 2.6, 15.1 Hz, IH), 4.10 (dd, J = 8.7, 15.1 Hz, IH), 3.90 (s, IH), 3.65 - 3.54 (m, 2H), 3.48 - 3.33 (m, 2H), 1.48 - 1.45 (m, 2H), 1.35 (s, 3H), 1.32 (s, 3H) and 1.14 - 1.11 (m, 2H) ppm.
47% With toluene-4-sulfonic acid In methanol; water at 80℃; for 0.75 h; (R)-l-(2,2-difluorobenzo[d] [l,3]dioxol-5-yl)-N-(l-((2,2-dimethyl-l,3- dioxolan-4-yl)methyl)-6-fluoro-2-(l-hydroxy-2-methylpropan-2-yl)-lH-indol-5- yl)cyclopropanecarboxamide (3.0 g, 5.4 mmol) was dissolved in methanol (52 mL). Water (5.2 mL) was added followed by p-TsOH.H20 (p-toluenesulfonic acid hydrate) (204 mg, 1.1 mmol). The reaction was heated at 80 °C for 45 minutes. The solution was concentrated and then partitioned between ethyl acetate and saturated NaHCCh solution. The ethyl acetate layer was dried over MgSC>4 and concentrated. The residue was purified by column chromatography (50-100 percent ethyl acetate - hexanes) to yield the product. (1.3 g, 47 percent, ee >98percent by SFC). ESI-MS m/z calc. 520.5, found 521.7 (M+l)+. Retention time 1.69 minutes. 1H NMR (400 MHz, DMSO- d6) 8.31 (s, 1H), 7.53 (s, 1H), 7.42 - 7.38 (m, 2H), 7.33 - 7.30 (m, 2H), 6.22 (s, 1H), 5.01 (d, J = 5.2 Hz, 1H), 4.90 (t, J = 5.5 Hz, 1H), 4.75 (t, J = 5.8 Hz, 1H), 4.40 (dd, J = 2.6, 15.1 Hz, 1H), 4.10 (dd, J = 8.7, 15.1 Hz, 1H), 3.90 (s, 1H), 3.65 - 3.54 (m, 2H), 3.48 - 3.33 (m, 2H), 1.48 - 1.45 (m, 2H), 1.35 (s, 3H), 1.32 (s, 3H) and 1.14 - 1.11 (m, 2H) ppm.
47% With toluene-4-sulfonic acid In methanol; water at 80℃; for 0.75 h; (R)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(1-((2,2-dimethyl-1,3- dioxolan-4-yl)methyl)-6-fluoro-2-(1-hydroxy-2-methylpropan-2-yl)-1H-indol-5- yl)cyclopropanecarboxamide (3.0 g, 5.4 mmol) was dissolved in methanol (52 mL). Water (5.2 mL) was added followed by p-TsOH.H2O (p-toluenesulfonic acid hydrate) (204 mg, 1.1 mmol). The reaction was heated at 80 °C for 45 minutes. The solution was concentrated and then partitioned between ethyl acetate and saturated NaHCO3solution. The ethyl acetate layer was dried over MgSO4and concentrated. The residue was purified by column chromatography (50-100 percent ethyl acetate - hexanes) to yield the product. (1.3 g, 47 percent, ee >98percent by SFC). ESI-MS m/z calc.520.5, found 521.7 (M+1)+. Retention time 1.69 minutes.1H NMR (400 MHz, DMSO-d6) δ 8.31 (s, 1H), 7.53 (s, 1H), 7.42 - 7.38 (m, 2H), 7.33 - 7.30 (m, 2H), 6.22 (s, 1H), 5.01 (d, J = 5.2 Hz, 1H), 4.90 (t, J = 5.5 Hz, 1H), 4.75 (t, J = 5.8 Hz, 1H), 4.40 (dd, J = 2.6, 15.1 Hz, 1H), 4.10 (dd, J = 8.7, 15.1 Hz, 1H), 3.90 (s, 1H), 3.65 - 3.54 (m, 2H), 3.48 - 3.33 (m, 2H), 1.48 - 1.45 (m, 2H), 1.35 (s, 3H), 1.32 (s, 3H) and 1.14 - 1.11 (m, 2H) ppm.
47% With water; toluene-4-sulfonic acid In methanol at 80℃; for 0.75 h; Step E:
(R)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(1-(2,3-dihydroxypropyl)-6-fluoro-2-(1-hydroxy-2-methylpropan-2-yl)-1H-indol-5-yl)cyclopropanecarboxamide
(R)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(1-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-6-fluoro-2-(1-hydroxy-2-methylpropan-2-yl)-1H-indol-5-yl)cyclopropanecarboxamide (3.0 g, 5.4 mmol) was dissolved in methanol (52 mL).
Water (5.2 mL) was added followed by p-TsOH.H2O (204 mg, 1.1 mmol).
The reaction was heated at 80° C. for 45 minutes.
The solution was concentrated and then partitioned between ethyl acetate and saturated NaHCO3 solution.
The ethyl acetate layer was dried over MgSO4 and concentrated.
The residue was purified by column chromatography (50-100percent ethyl acetate hexanes) to yield the product as a cream colored foamy solid (1.3 g, 47percent, ee>98percent by SFC). ESI-MS m/z calc. 520.5, found 521.7 (M+1)+.
Retention time 1.69 minutes. 1NMR (400 MHz, DMSO-d6) δ 8.31 (s, 1H), 7.53 (s, 1H), 7.42-7.38 (m, 2H), 7.33-7.30 (m, 2H), 6.22 (s, 1H), 5.01 (d, J=5.2 Hz, 1H), 4.90 (t, J=5.5 Hz, 1H), 4.75 (t, J=5.8 Hz, 1H), 4.40 (dd, J=2.6, 15.1 Hz, 1H), 4.10 (dd, J=8.7, 15.1 Hz, 1H), 3.90 (s, 1H), 3.65-3.54 (m, 2H), 3.48-3.33 (m, 2H), 1.48-1.45 (m, 2H), 1.35 (s, 3H), 1.32 (s, 3H) and 1.14-1.11 (m, 2H) ppm.
47% With toluene-4-sulfonic acid In methanol; water at 80℃; for 0.75 h; (R)- 1 -(2,2-difluorobenzo [d] [ 1 ,3]dioxol-5-yl)-N-( l-((2,2-dimethyl- 1 ,3-dioxolan- 4-yl)methyl)-6-fluoro-2-(l-hydroxy-2-methylpropan-2-yl)- lH-indol-5- yl)cyclopropanecarboxamide (3.0 g, 5.4 mmol) was dissolved in methanol (52 mL). Water (5.2 mL) was added followed by p-TsOH.H20 (204 mg, 1.1 mmol). The reaction was heated at 80 °C for 45 minutes. The solution was concentrated and then partitioned between ethyl acetate and saturated NaHC03 solution. The ethyl acetate layer was dried over MgS04 and concentrated. The residue was purified by column chromatography (50- 100 percent ethyl acetate - hexanes) to yield the product as a cream colored foamy solid. (1.3 g, 47 percent, ee >98percent by SFC). ESI-MS m/z calc. 520.5, found 521.7 (M+l)+. Retention time 1.69 minutes. lH NMR (400 MHz, DMSO- 6) δ 8.31 (s, 1H), 7.53 (s, 1H), 7.42 - 7.38 (m, 2H), 7.33 - 7.30 (m, 2H), 6.22 (s, 1H), 5.01 (d, J = 5.2 Hz, 1H), 4.90 (t, J = 5.5 Hz, 1H), 4.75 (t, J = 5.8 Hz, 1H), 4.40 (dd, J = 2.6, 15.1 Hz, 1H), 4.10 (dd, J = 8.7, 15.1 Hz, 1H), 3.90 (s, 1H), 3.65 - 3.54 (m, 2H), 3.48 - 3.33 (m, 2H), 1.48 - 1.45 (m, 2H), 1.35 (s, 3H), 1.32 (s, 3H) and 1.14 - 1.11 (m, 2H) ppm.
47% With toluene-4-sulfonic acid In methanol; water at 80℃; for 0.75 h; 1003231 (R)- 1 -(2,2-difluorobenzo[d] [1,3 ]dioxol-5-yl)-N-( 1 -((2,2-dimethyl- 1,3 -dioxolan4-yl)methyl)-6-fluoro-2-( 1 -hydroxy-2-methylpropan-2-yl)- 1 H-indol-5- yl)cyclopropanecarboxamide (3.0 g, 5.4 mmol) was dissolved in methanol (52 mL). Water (5.2 mL) was added followed by p-T5OH.H20 (204 mg, 1.1 mmol). The reaction was heated at 80 °C for 45 minutes. The solution was concentrated and then partitioned between ethyl acetate and saturated NaHCO3 solution. The ethyl acetate layer was dried over MgSO4 and concentrated. The residue was purified by column chromatography (50- 100 percent ethyl acetate - hexanes) to yield the product as a cream colored foamy solid. (1.3 g, 47 percent, ee >98percent by SFC). ESI-MS m/z calc. 520.5, found 521.7 (M+1)t Retention time1.69 minutes. ‘HNMR(400 IVIHz, DMSO-d6) 8.31 (s, 1H), 7.53 (s, 1H), 7.42-7.38 (m, 2H), 7.33 - 7.30 (m, 2H), 6.22 (s, 1H), 5.01 (d, J = 5.2 Hz, 1H), 4.90 (t, J = 5.5 Hz, 1H), 4.75 (t, J = 5.8 Hz, 1H), 4.40 (dd, J = 2.6, 15.1 Hz, 1H), 4.10 (dd, J = 8.7, 15.1 Hz, 1H), 3.90 (s, 1H), 3.65 - 3.54 (m, 2H), 3.48 - 3.33 (m, 2H), 1.48 - 1.45 (m, 2H), 1.35 (s, 3H), 1.32 (s, 3H) and 1.14-1.11 (m, 2H) ppm.
47% With toluene-4-sulfonic acid In methanol; water at 80℃; for 0.75 h; (R)- 1 -(2,2-difluorobenzo [d] [1,3]dioxol-5-yl)-N-(l-((2,2-dimethyl- 1,3-dioxolan- 4-yl)methyl)-6-fluoro-2-(l-hydroxy-2-methylpropan-2-yl)- lH-indol-5- yl)cyclopropanecarboxamide (3.0 g, 5.4 mmol) was dissolved in methanol (52 mL). Water (5.2 mL) was added followed by p-TsOH.H20 (204 mg, 1.1 mmol). The reaction was heated at 80 °C for 45 minutes. The solution was concentrated and then partitioned between ethyl acetate and saturated NaHC03 solution. The ethyl acetate layer was dried over MgS04 and concentrated. The residue was purified by column chromatography (50- 100 percent ethyl acetate - hexanes) to yield the product as a cream colored foamy solid. (1.3 g, 47 percent, ee >98percent by SFC). ESI-MS m/z calc. 520.5, found 521.7 (M+l)+. Retention time 1.69 minutes. lH NMR (400 MHz, DMSO- 6) δ 8.31 (s, 1H), 7.53 (s, 1H), 7.42 - 7.38 (m, 2H), 7.33 - 7.30 (m, 2H), 6.22 (s, 1H), 5.01 (d, J = 5.2 Hz, 1H), 4.90 (t, J = 5.5 Hz, 1H), 4.75 (t, J = 5.8 Hz, 1H), 4.40 (dd, J = 2.6, 15.1Hz, 1H), 4.10 (dd, J = 8.7, 15.1Hz, 1H), 3.90 (s, 1H), 3.65 - 3.54 (m, 2H), 3.48 - 3.33 (m, 2H), 1.48 - 1.45 (m, 2H), 1.35 (s, 3H), 1.32 (s, 3H) and 1.14 - 1.11 (m, 2H) ppm.
47% With toluene-4-sulfonic acid In methanol; water at 80℃; for 0.75 h; (R)- 1 -(2,2-difluorobenzo [d] [1,3]dioxol-5-yl)-N-(l-((2,2-dimethyl- 1,3- dioxolan-4-yl)methyl)-6-fluoro-2-(l-hydroxy-2-methylpropan-2-yl)- lH-indol-5- yl)cyclopropanecarboxamide (3.0 g, 5.4 mmol) was dissolved in methanol (52 mL). Water (5.2 mL) was added followed by p-TsOH.H20 (204 mg, 1.1 mmol). The reaction was heated at 80 °C for 45 minutes. The solution was concentrated and then partitioned between ethyl acetate and saturated NaHC03 solution. The ethyl acetate layer was dried over MgS04 and concentrated. The residue was purified by column chromatography (50- 100 percent ethyl acetate - hexanes) to yield the product as a cream colored foamy solid. (1.3 g, 47 percent, ee >98percent by SFC). ESI-MS m/z calc. 520.5, found 521.7 (M+l)+. Retention time 1.69 minutes. lH NMR (400 MHz, DMSO- 6) δ 8.31 (s, 1H), 7.53 (s, 1H), 7.42 - 7.38 (m, 2H), 7.33 - 7.30 (m, 2H), 6.22 (s, 1H), 5.01 (d, J = 5.2 Hz, 1H), 4.90 (t, J = 5.5 Hz, 1H), 4.75 (t, J = 5.8 Hz, 1H), 4.40 (dd, J = 2.6, 15.1Hz, 1H), 4.10 (dd, J = 8.7, 15.1Hz, 1H), 3.90 (s, 1H), 3.65 - 3.54 (m, 2H), 3.48 - 3.33 (m, 2H), 1.48 - 1.45 (m, 2H), 1.35 (s, 3H), 1.32 (s, 3H) and 1.14 - 1.11 (m, 2H) ppm.

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[2] Patent: WO2018/64632, 2018, A1, . Location in patent: Paragraph 00198; 00207; 00208.
[3] Patent: WO2018/107100, 2018, A1, . Location in patent: Paragraph 00217; 00226; 00227.
[4] Patent: US2018/280349, 2018, A1, . Location in patent: Paragraph 0088; 0093.
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[8] Patent: WO2019/18395, 2019, A1, . Location in patent: Paragraph 00175.
 

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