Trifluoroacetic acid → Trifluoroacetic acid

HRID 474287Notes

Reaction equation

HRID 474287 reaction equation
[NH2:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([O:10][CH2:11][CH:12]([OH:16])[CH2:13][CH2:14][NH2:15])[CH:3]=1.[C:17]([OH:23])([C:19]([F:22])([F:21])[F:20])=[O:18].[Cl:24][C:25]1[N:26]=[C:27](Cl)[C:28]2[CH2:33][CH2:32][CH:31]([C:34]3[CH:39]=[CH:38][C:37]([F:40])=[CH:36][CH:35]=3)[C:29]=2[N:30]=1.C(N(C(C)C)C(C)C)C>C(#N)C>[NH2:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([O:10][CH2:11][CH:12]([OH:16])[CH2:13][CH2:14][NH:15][C:27]2[C:28]3[CH2:33][CH2:32][CH:31]([C:34]4[CH:35]=[CH:36][C:37]([F:40])=[CH:38][CH:39]=4)[C:29]=3[N:30]=[C:25]([Cl:24])[N:26]=2)[CH:3]=1.[C:17]([OH:23])([C:19]([F:22])([F:21])[F:20])=[O:18]

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 580754242,4-Dichloro-7-(4-fluorophenyl)-6,7-dihydro-5H-cyclopenta[D]pyrimidineHCID 666661314-Amino-2-(4-amino-2-hydroxybutoxy)benzonitrile

Product 2

HCID 6422Trifluoroacetic acidYield 22.75%HCID 866681224-amino-2-(4-(2-chloro-7-(4-fluorophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-ylamino)-2-hydroxybutoxy)benzonitrile

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

The mixture of 4-amino-2-(4-amino-2-hydroxybutoxy)benzonitrile, 2 TFA salt (Preparation Z, 50 mg, 0.111 mmol), 2,4-dichloro-7-(4-fluorophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrimidine (Preparation R, 31.5 mg, 0.111 mmol) and N-ethyl-N-isopropylpropan-2-amine (97 μL, 0.556 mmol) in acetonitrile (556 μL) was stirred at rt for 24 h. The reaction mixture was concentrated and purified by Prep-HPLC to obtain 4-amino-2-(4-(2-chloro-7-(4-fluorophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-ylamino)-2-hydroxybutoxy)benzonitrile, TFA (14.73 mg, 22.75% yield). LC-MS (M+H)+=468.2. 1H NMR (500 MHz, methanol-d4) δ 7.27-7.15 (m, 3H), 7.14-7.01 (m, 2H), 6.40-6.24 (m, 2H), 4.44-4.33 (m, 1H), 4.17-4.04 (m, 2H), 4.03-3.95 (m, 1H), 3.89-3.66 (m, 2H), 2.94-2.81 (m, 1H), 2.81-2.67 (m, 2H), 2.14 (td, J=7.5, 4.0 Hz, 1H), 2.10-2.00 (m, 1H), 1.95 (dd, J=14.0, 6.4 Hz, 1H).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. custompurified by Prep-HPLC

Sources & evidence

ORD record
ord-aa5fbaf636db4e83acd5c8dda75eb72f
Source dataset
uspto-grants-2014_01
Patent number
US08637523B2

Reaction notes

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