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Water → 2-(4-(1-(4-(4-((1-(Pyrrolidin-1-ylmethyl)cyclopropyl)methylcarbamoyl)phenylamino)-6-(2,2,2-trifluoroethoxy)-1,3,5-triazin-2-ylamino)cyclopropyl)phenoxy)acetic acid

HRID 1618341
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HRID 1618341 반응식
[N:1]1([CH2:6][C:7]2([CH2:10][NH:11][C:12]([C:14]3[CH:19]=[CH:18][C:17]([NH:20][C:21]4[N:26]=[C:25]([O:27][CH2:28][C:29]([F:32])([F:31])[F:30])[N:24]=[C:23]([NH:33][C:34]5([C:37]6[CH:49]=[CH:48][C:40]([O:41][CH2:42][C:43]([O:45]CC)=[O:44])=[CH:39][CH:38]=6)[CH2:36][CH2:35]5)[N:22]=4)=[CH:16][CH:15]=3)=[O:13])[CH2:9][CH2:8]2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[Li+].[OH-].O>C1COCC1>[N:1]1([CH2:6][C:7]2([CH2:10][NH:11][C:12]([C:14]3[CH:15]=[CH:16][C:17]([NH:20][C:21]4[N:26]=[C:25]([O:27][CH2:28][C:29]([F:32])([F:30])[F:31])[N:24]=[C:23]([NH:33][C:34]5([C:37]6[CH:49]=[CH:48][C:40]([O:41][CH2:42][C:43]([OH:45])=[O:44])=[CH:39][CH:38]=6)[CH2:36][CH2:35]5)[N:22]=4)=[CH:18][CH:19]=3)=[O:13])[CH2:9][CH2:8]2)[CH2:2][CH2:3][CH2:4][CH2:5]1
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참가 물질

5

반응물 3

HCID 962WaterHCID 3939Lithium HydroxideHCID 68033160Ethyl 2-(4-(1-(4-(4-((1-(pyrrolidin-1-ylmethyl)cyclopropyl)methylcarbamoyl)phenylamino)-6-(2,2,2-trifluoroethoxy)-1,3,5-triazin-2-ylamino)cyclopropyl)phenoxy)acetate

생성물 1

HCID 680331262-(4-(1-(4-(4-((1-(Pyrrolidin-1-ylmethyl)cyclopropyl)methylcarbamoyl)phenylamino)-6-(2,2,2-trifluoroethoxy)-1,3,5-triazin-2-ylamino)cyclopropyl)phenoxy)acetic acid수율 50.6%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

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온도
65 °C

실험 절차

ethyl 2-(4-(1-(4-(4-((1-(pyrrolidin-1-ylmethyl)cyclopropyl)methylcarbamoyl)phenylamino)-6-(2,2,2-trifluoroethoxy)-1,3,5-triazin-2-ylamino)cyclopropyl)phenoxy)acetate (268 mg, 0.392 mmol) was dissolved in THF (Ratio: 1.000, Volume: 2 mL) then LiOH (46.9 mg, 1.960 mmol) and Water (Ratio: 1.000, Volume: 2 mL) were added and the reaction was heated to 65° C. for 2 h. The solvent was removed under vacuum and water was added back to the flask and the pH adjusted to ˜7 with 1N HCl. A solid precipitated out of solution and this was collected, washed with water, and dried to give 2-(4-(1-(4-(4-((1-(pyrrolidin-1-ylmethyl)cyclopropyl)methylcarbamoyl)phenylamino)-6-(2,2,2-trifluoroethoxy)-1,3,5-triazin-2-ylamino)cyclopropyl)phenoxy)acetic acid (130 mg). 1H NMR (400 MHz, MeOD) δ ppm 0.62-0.70 (m, 2H), 0.94-1.02 (m, 2H), 1.15-1.34 (m, 4H), 2.10 (br. s., 4H), 3.08 (br. s., 2H), 3.30-3.33 (m, 4H), 3.49 (s, 2H), 4.51 (s, 2H), 4.86-4.93 (m, 2H), 6.85-6.94 (m, 2H), 7.08-7.16 (m, 2H), 7.16-7.25 (m, 2H), 7.42-7.54 (m, 2H); LC-MS (Condition A), MS m/z (M++H) 656.1.

후처리

  1. customThe solvent was removed under vacuum and water
  2. additionwas added back to the flask
  3. customA solid precipitated out of solution
  4. customthis was collected
  5. washwashed with water
  6. customdried

출처 및 근거

ORD 기록
ord-0ba21b97729e4e74b497771113bf4602
출처 데이터셋
uspto-grants-2014_07
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08765944B2

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