Diisopropylethylamine → 4-(4-(1-(4-chlorophenyl)cyclopropylamino)-6-(2,2,2-trifluoroethoxy)-1,3,5-triazin-2-ylamino)-N-(2,2-dimethyl-3-(2-oxo-2-(pyrrolidin-1-yl)acetamido)propyl)-3-fluorobenzamide

HRID 1407047Notes

Reaction equation

HRID 1407047 reaction equation
[NH2:1][CH2:2][C:3]([CH3:40])([CH3:39])[CH2:4][NH:5][C:6](=[O:38])[C:7]1[CH:12]=[CH:11][C:10]([NH:13][C:14]2[N:19]=[C:18]([NH:20][C:21]3([C:24]4[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][CH:25]=4)[CH2:23][CH2:22]3)[N:17]=[C:16]([O:31][CH2:32][C:33]([F:36])([F:35])[F:34])[N:15]=2)=[C:9]([F:37])[CH:8]=1.[O:41]=[C:42]([N:46]1[CH2:50][CH2:49][CH2:48][CH2:47]1)[C:43](O)=[O:44].F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.CCN(C(C)C)C(C)C>CN(C=O)C>[Cl:30][C:27]1[CH:28]=[CH:29][C:24]([C:21]2([NH:20][C:18]3[N:17]=[C:16]([O:31][CH2:32][C:33]([F:35])([F:36])[F:34])[N:15]=[C:14]([NH:13][C:10]4[CH:11]=[CH:12][C:7]([C:6]([NH:5][CH2:4][C:3]([CH3:40])([CH3:39])[CH2:2][NH:1][C:43](=[O:44])[C:42](=[O:41])[N:46]5[CH2:50][CH2:49][CH2:48][CH2:47]5)=[O:38])=[CH:8][C:9]=4[F:37])[N:19]=3)[CH2:23][CH2:22]2)=[CH:25][CH:26]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 3150858Oxo(pyrrolidin-1-yl)acetic acidHCID 86691684HCID 86691684, compound

Product 1

HCID 866916854-(4-(1-(4-chlorophenyl)cyclopropylamino)-6-(2,2,2-trifluoroethoxy)-1,3,5-triazin-2-ylamino)-N-(2,2-dimethyl-3-(2-oxo-2-(pyrrolidin-1-yl)acetamido)propyl)-3-fluorobenzamideYield 14.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of N-(3-amino-2,2-dimethylpropyl)-4-(4-(1-(4-chlorophenyl)cyclopropylamino)-6-(2,2,2-trifluoroethoxy)-1,3,5-triazin-2-ylamino)-3-fluorobenzamide (80 mg, 0.14 mmol) and 2-oxo-2-(pyrrolidin-1-yl)acetic acid (20 mg, 0.137 mmol) in DMF (2 mL) were added O-(benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium tetrafluoroborate (66 mg, 0.21 mmol) and iPr2NEt (0.050 ml, 0.28 mmol). After stirring at rt for 16 hs, the mixture was purified by preparative HPLC to give 4-(4-(1-(4-chlorophenyl)cyclopropylamino)-6-(2,2,2-trifluoroethoxy)-1,3,5-triazin-2-ylamino)-N-(2,2-dimethyl-3-(2-oxo-2-(pyrrolidin-1-yl)acetamido)propyl)-3-fluorobenzamide (14.4 mg, 14%) as product. 1H NMR (400 MHz, CHLOROFORM-d) 8 ppm 1.01 (6H, s), 1.42 (4H, m), 1.81-2.02 (4H, m), 3.14 (2H, m), 3.29 (2H, d, J=6.0 Hz), 3.60 (2H, t, J=6.9 Hz), 3.91-4.12 (2H, m), 4.70-4.80 (2H, m), 7.14-7.38 (3H, m), 7.48-7.59 (1H, m), 7.69-7.80 (1H, m), 7.94-8.06 (1H, m), 8.24-8.31 (1H, m).

Workup

  1. customthe mixture was purified by preparative HPLC

Sources & evidence

ORD record
ord-25f082c1be3745f1b72d069e84e53beb
Source dataset
uspto-grants-2014_12
Patent number
US08916702B2

Reaction notes

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