Diisopropylethylamine → 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

HRID 1618340Notes

Reaction equation

HRID 1618340 reaction equation
[CH2:1]([O:3][C:4](=[O:39])[CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2([NH:16][C:17]3[N:22]=[C:21]([O:23][CH2:24][C:25]([F:28])([F:27])[F:26])[N:20]=[C:19]([NH:29][C:30]4[CH:38]=[CH:37][C:33]([C:34](O)=[O:35])=[CH:32][CH:31]=4)[N:18]=3)[CH2:15][CH2:14]2)=[CH:9][CH:8]=1)[CH3:2].[N:40]1([CH2:45][C:46]2([CH2:49][NH2:50])[CH2:48][CH2:47]2)[CH2:44][CH2:43][CH2:42][CH2:41]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>C(Cl)Cl>[N:40]1([CH2:45][C:46]2([CH2:49][NH:50][C:34]([C:33]3[CH:32]=[CH:31][C:30]([NH:29][C:19]4[N:20]=[C:21]([O:23][CH2:24][C:25]([F:27])([F:28])[F:26])[N:22]=[C:17]([NH:16][C:13]5([C:10]6[CH:9]=[CH:8][C:7]([O:6][CH2:5][C:4]([O:3][CH2:1][CH3:2])=[O:39])=[CH:12][CH:11]=6)[CH2:15][CH2:14]5)[N:18]=4)=[CH:38][CH:37]=3)=[O:35])[CH2:48][CH2:47]2)[CH2:44][CH2:43][CH2:42][CH2:41]1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 280647661-{1-[(Pyrrolidin-1-yl)methyl]cyclopropyl}methanamineHCID 680331374-(4-(1-(4-(2-Ethoxy-2-oxoethoxy)phenyl)cyclopropylamino)-6-(2,2,2-trifluoroethoxy)-1,3,5-triazin-2-ylamino)benzoic acid

Product 1

HCID 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)acetateYield 65%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

4-(4-(1-(4-(2-ethoxy-2-oxoethoxy)phenyl)cyclopropylamino)-6-(2,2,2-trifluoroethoxy)-1,3,5-triazin-2-ylamino)benzoic acid (330 mg, 0.603 mmol), (1-(pyrrolidin-1-ylmethyl)cyclopropyl)methanamine (112 mg, 0.723 mmol), HATU (344 mg, 0.904 mmol), and Hunig's Base (0.526 mL, 3.01 mmol) were stirred in DCM (Volume: 5 mL) for 16 h. The solvent was removed and the crude material was purified by silica gel chromatography using EtOAc then 5% DCM/MeOH to give 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). LC-MS (Condition A), MS m/z (M++H) 684.1.

Workup

  1. customThe solvent was removed
  2. customthe crude material was purified by silica gel chromatography

Sources & evidence

ORD record
ord-f6b5f697a9d64771b5bd8d35fe8b5379
Source dataset
uspto-grants-2014_07
Patent number
US08765944B2

Reaction notes

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