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 1618341Notes

Reaction equation

HRID 1618341 reaction equation
[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

Participants

5

Reactant 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

Product 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 acidYield 50.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
65 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-0ba21b97729e4e74b497771113bf4602
Source dataset
uspto-grants-2014_07
Patent number
US08765944B2

Reaction notes

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