Guanidine Hydrochloride → HCID 58235128, compound

HRID 1896665Notes

Reaction equation

HRID 1896665 reaction equation
C1(C2N=CN(C3CCNCC3)C=2C2C=CN=C(N)N=2)C=CC=CC=1.C(C1N(C2CCN(C(OC(C)(C)C)=O)CC2)C=NC=1C1C=CC=CC=1)(=O)C.CNC1N=C(C2N(C3CCNCC3)C=NC=2C2C=CC=CC=2)C=CN=1.Cl.NC(N)=N.O1C=CC(C=O)=N1.F[C:90]1[CH:95]=[CH:94][C:93]([C:96]2[N:97]=[CH:98][N:99]([CH:109]3[CH2:114][CH2:113][N:112]([CH2:115][C:116]4[CH:120]=[CH:119][O:118][N:117]=4)[CH2:111][CH2:110]3)[C:100]=2[C:101]2[CH:106]=[CH:105][N:104]=[C:103]([NH:107]C)[N:102]=2)=[CH:92][CH:91]=1>>[O:118]1[CH:119]=[CH:120][C:116]([CH2:115][N:112]2[CH2:113][CH2:114][CH:109]([N:99]3[C:100]([C:101]4[CH:106]=[CH:105][N:104]=[C:103]([NH2:107])[N:102]=4)=[C:96]([C:93]4[CH:94]=[CH:95][CH:90]=[CH:91][CH:92]=4)[N:97]=[CH:98]3)[CH2:110][CH2:111]2)=[N:117]1

Participants

7

Reactant 6

HCID 5742Guanidine HydrochlorideHCID 183730781,2-Oxazole-3-carbaldehydeHCID 57461731HCID 57461731, compoundHCID 58235101tert-butyl 4-(5-acetyl-4-phenyl-1H-imidazol-1-yl)piperidine-1-carboxylateHCID 58235131HCID 58235131, compoundHCID 582351384-{4-(4-Fluorophenyl)-1-[1-(isoxazol-3-ylmethyl)piperidin-4-yl]-1H-imidazol-5-yl}-N-methylpyrimidin-2-amine

Product 1

HCID 58235128HCID 58235128, compound

Procedure

4-(4-Phenyl-1-piperidin-4-yl-1H-imidazol-5-yl)pyrimidin-2-amine [C27, prepared from tert-butyl 4-(5-acetyl-4-phenyl-1H-imidazol-1-yl)piperidine-1-carboxylate (C24) in a manner similar to the synthesis of N-methyl-4-(4-phenyl-1-piperidin-4-yl-1H-imidazol-5-yl)pyrimidin-2-amine (C26) described in Example 12, but using guanidine hydrochloride in place of N-methylguanidine hydrochloride] was reacted with isoxazole-3-carbaldehyde according to the general procedure for the synthesis of 4-{4-(4-fluorophenyl)-1-[1-(isoxazol-3-ylmethyl)piperidin-4-yl]-1H-imidazol-5-yl}-N-methylpyrimidin-2-amine (5) in Example 5. 4-{1-[1-(Isoxazol-3-ylmethyl)piperidin-4-yl]-4-phenyl-1H-imidazol-5-yl}pyrimidin-2-amine (free base of 13) was obtained as a yellow solid. Yield: 101 mg, 0.252 mmol, 29%. 1H NMR (400 MHz, CDCl3) δ 1.97-2.08 (m, 2H), 2.12-2.24 (m, 4H), 3.03 (br d, J=12 Hz, 2H), 3.69 (s, 2H), 4.59 (tt, J=11.8, 4.0 Hz, 1H), 5.07 (br s, 2H), 6.41 (d, J=1.7 Hz, 1H), 6.54 (d, J=5.2 Hz, 1H), 7.27-7.34 (m, 3H), 7.46-7.50 (m, 2H), 7.78 (s, 1H), 8.17 (d, J=5.2 Hz, 1H), 8.40 (br d, J=1.5 Hz, 1H). This solid was dissolved in ethyl acetate, treated with a solution of hydrogen chloride in diethyl ether (2 N, 1 equivalent) and allowed to stir for 18 hours. The resulting solid was collected by filtration to provide the title product as a light yellow solid. Yield: 70 mg, 0.16 mmol, 19%.

Sources & evidence

ORD record
ord-c43428f8c65e4688aa763c24eb5b6b6b
Source dataset
uspto-grants-2013_08
Patent number
US08518944B2

Reaction notes

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