Dimethylformamide → HCID 136348819, compound

HRID 1865438Notes

Reaction equation

HRID 1865438 reaction equation
C1CN([P+](ON2N=NC3C=C[CH:23]=[CH:24][C:19]2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.[Cl:34][C:35]1[CH:36]=[C:37]([C:42]2[CH:46]=[C:45]([C:47]3[NH:51][C:50]4[CH:52]=[C:53]([O:56][C:57]([F:60])([F:59])[F:58])[CH:54]=[CH:55][C:49]=4[N:48]=3)[N:44]([CH2:61][C:62]3[CH:70]=[CH:69][C:65](C(O)=O)=[CH:64][CH:63]=3)[N:43]=2)[CH:38]=[C:39]([Cl:41])[CH:40]=1.Cl.C(NC[CH2:78][C:79]([OH:81])=[O:80])(C)(C)C.[CH3:82]CN(C(C)C)C(C)C.[CH3:91][N:92]([CH:94]=[O:95])C>>[Cl:41][C:39]1[CH:38]=[C:37]([C:42]2[CH:46]=[C:45]([C:47]3[NH:51][C:50]4[CH:52]=[C:53]([O:56][C:57]([F:60])([F:58])[F:59])[CH:54]=[CH:55][C:49]=4[N:48]=3)[N:44]([CH2:61][C:62]3[CH:70]=[CH:69][C:65]([C:94]([NH:92][CH2:91][CH2:78][C:79]([O:81][C:24]([CH3:23])([CH3:19])[CH3:82])=[O:80])=[O:95])=[CH:64][CH:63]=3)[N:43]=2)[CH:36]=[C:35]([Cl:34])[CH:40]=1

Participants

6

Reactant 5

HCID 6228Dimethylformamide2×HCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 17567357N-tert-Butyl-beta-alanine--hydrogen chloride (1/1)HCID 136348820HCID 136348820, compound

Product 1

HCID 136348819HCID 136348819, compound

Procedure

A solution of PyBOP (38 mg, 70 umol) in DMF (0.1 ml) was added to a mixture of 4-({3-(3,5-dichlorophenyl)-5-[6-(trifluoromethoxy)-1H-benzimidazol-2-yl]-1H-pyrazol-1-yl}methyl)benzoic acid (20 mg, 36 umol), tert-butyl β-alanine hydrochloride (27 mg, 4 eq.), DIEA (40 ul, 6 eq.) in DMF (0.3 ml). The reaction was quenched with CH3CN:water (5% TFA) and purified with reverse phase HPLC to give tert-butyl N-[4-({3-(3,5-dichlorophenyl)-5-[6-(trifluoromethoxy)-1H-benzimidazol-2-yl]-1H-pyrazol-1-yl}methyl)benzoyl]-β-alaninate as an oil residue. This was treated with TFA/DCM (1:2) and the product was lyophilized to give N-[4-({3-(3,5-Dichlorophenyl)-5-[6-(trifluoromethoxy)-1H-benzimidazol-2-yl]-1H-pyrazol-1-yl}methyl)benzoyl]-β-alanine as a white powder. NMR (500 MHz, DMSO-d6) δ: 2.43 (t, 2H); 3.4 (q, 2H); 6.18 (s, 2H); 7.26 (br d, J=9.2 Hz, 1H); 7.38 (d, J=8.5 Hz, 2H); 7.59 (s, 1H); 7.61 (t, J=1.9 Hz, 1H); 7.67 (br s, 1H); 7.72 (d, J=8.5 Hz, 2H); 7.74 (br d, J=9.2 Hz, 1H); 7.82 (d, J=1.9 Hz, 2H). MS Cald for C28H20Cl2F3N5O4: 617.08; Obsd (M+1): 618.21.

Workup

  1. customThe reaction was quenched with CH3CN
  2. customwater (5% TFA) and purified with reverse phase HPLC

Sources & evidence

ORD record
ord-ca836b7968784b6e8eaed8b621ff4d70
Source dataset
uspto-grants-2009_12
Patent number
US07625938B2

Reaction notes

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