Cyanoacetic acid → HCID 71467626, compound

HRID 2281075Notes

Reaction equation

HRID 2281075 reaction equation
[Cl:1][C:2]1[C:10]2[N:9]=[N:8][N:7]([CH2:11][CH:12]3[CH2:14][CH2:13]3)[C:6]=2[CH:5]=[CH:4][C:3]=1[C:15]1[CH:20]=[CH:19][C:18]([CH2:21][N:22]2[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]2)=[CH:17][CH:16]=1.[C:28]([CH2:30][C:31](O)=[O:32])#[N:29].F[P-](F)(F)(F)(F)F.N1(O[P+](N2CCCC2)(N2CCCC2)N2CCCC2)C2C=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C>ClCCl>[Cl:1][C:2]1[C:10]2[N:9]=[N:8][N:7]([CH2:11][CH:12]3[CH2:14][CH2:13]3)[C:6]=2[CH:5]=[CH:4][C:3]=1[C:15]1[CH:16]=[CH:17][C:18]([CH2:21][N:22]2[CH2:23][CH2:24][N:25]([C:31](=[O:32])[CH2:30][C:28]#[N:29])[CH2:26][CH2:27]2)=[CH:19][CH:20]=1

Participants

6

Reactant 4

HCID 9740Cyanoacetic acidHCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 70978096HCID 70978096, compound

Product 1

HCID 71467626HCID 71467626, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirring solution of 4-chloro-1-(cyclopropylmethyl)-5-[4-(piperazin-1-ylmethyl)phenyl]-1H-benzotriazole (Example 71, 15 mg, 0.039 mmol) in dichloromethane (530 uL) was added cyanoacetic acid (6.7 mg, 0.079 mmol) and (benzotriazol-1-yloxy)tripyrrolidinophosphonium hexafluorophosphate (31 mg, 0.059 mmol) and diisopropylethylamine (34 uL, 0.20 mmol). After stirring for 2 hours at ambient temperature, the mixture was concentrated in vacuo and the residue was purified by preparative reverse phase HPLC (95:5 to 5:95; water containing 0.1% trifluoroacetic acid:acetonitrile containing 0.1% trifluoroacetic acid) to afford the titled compound: 1H-NMR (400 MHz, d6-DMSO) δ 8.01 (1H, d, J=8.5 Hz), 7.66 (2H, d, J=7.7 Hz), 7.62 (2H, d, J=7.7 Hz), 7.60 (1H, d, J=8.6 Hz), 4.68 (2H, d, J=7.4 Hz), 4.39 (1H, br s), 2.57-2.46 (10H, m), 1.75-1.72 (2H, m), 1.49-1.38 (1H, m), 0.60-0.56 (2H, m), 0.52-0.49 (2H, m) ppm high resolution mass spectrometry (ES+) m/z 449.1862 [(M+H)+; calculated for C24H26ClN6O: 449.1851].

Workup

  1. concentrationthe mixture was concentrated in vacuo
  2. customthe residue was purified by preparative reverse phase HPLC (95:5 to 5:95; water containing 0.1% trifluoroacetic acid:acetonitrile containing 0.1% trifluoroacetic acid)

Sources & evidence

ORD record
ord-298470d993704abcaa065853cf05d9a2
Source dataset
uspto-grants-2015_09
Patent number
US09139576B2

Reaction notes

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