Formamidine acetate → 4-[4-(4-Fluorophenyl)-1-pyrrolidin-3-yl-1H-imidazol-5-yl]pyrimidine

HRID 1896657Notes

Reaction equation

HRID 1896657 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[CH:10][N:11]([CH:19]3[CH2:23][CH2:22][N:21](C(OC(C)(C)C)=O)[CH2:20]3)[C:12]=2[C:13]2[CH:18]=[CH:17][N:16]=[CH:15][N:14]=2)=[CH:4][CH:3]=1.NC1N=C(C2N(C3CCN(C(OC(C)(C)C)=O)C3)C=NC=2C2C=CC(F)=CC=2)C=CN=1.C(O)(=O)C.C(N)=N.FC1C=CC(C2N=CN(C3CCNC3)C=2C2C=CN=C(N)N=2)=CC=1>>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[CH:10][N:11]([CH:19]3[CH2:23][CH2:22][NH:21][CH2:20]3)[C:12]=2[C:13]2[CH:18]=[CH:17][N:16]=[CH:15][N:14]=2)=[CH:4][CH:3]=1

Participants

5

Reactant 4

HCID 160693Formamidine acetateHCID 57461720HCID 57461720, compound2×HCID 57461721HCID 57461721, compoundHCID 57461722tert-Butyl 3-[4-(4-fluorophenyl)-5-pyrimidin-4-yl-1H-imidazol-1-yl]pyrrolidine-1-carboxylate

Product 1

HCID 574617254-[4-(4-Fluorophenyl)-1-pyrrolidin-3-yl-1H-imidazol-5-yl]pyrimidine

Procedure

tert-Butyl 3-[4-(4-fluorophenyl)-5-pyrimidin-4-yl-1H-imidazol-1-yl]pyrrolidine-1-carboxylate (C19, prepared according to the general procedure for the synthesis of tert-butyl 3-[5-(2-aminopyrimidin-4-yl)-4-(4-fluorophenyl)-1H-imidazol-1-yl]pyrrolidine-1-carboxylate (C17) in Example 7, except that formamidine acetate was used in place of guanidine hydrochloride) was converted to the product using conditions similar to those employed for transformation of tert-butyl 3-[5-(2-aminopyrimidin-4-yl)-4-(4-fluorophenyl)-1H-imidazol-1-yl]pyrrolidine-1-carboxylate (C17) to 4-[4-(4-fluorophenyl)-1-pyrrolidin-3-yl-1H-imidazol-5-yl]pyrimidin-2-amine (C18) in Example 7. The product was obtained as a solid. Yield: 1.58 g, 5.11 mmol, 70%. LCMS m/z 310.4 (M+1). 1H NMR (400 MHz, CD3OD) δ 2.16 (m, 1H), 2.37 (m, 1H), 3.02 (m, 1H), 3.09 (dd, J=12.2, 4.6 Hz, 1H), 3.21 (m, 1H), 3.3 (m, 1H, assumed; obscured by solvent signal), 5.32 (m, 1H), 7.09 (dd, J=8.6, 8.6 Hz, 2H), 7.26 (d, J=5.2 Hz, 1H), 7.38 (dd, J=8.3, 5.5 Hz, 2H), 8.15 (s, 1H), 8.63 (d, J=5.5 Hz, 1H), 9.28 (s, 1H).

Workup

  1. customThe product was obtained as a solid

Sources & evidence

ORD record
ord-f9e9f4b0b379441494a53aab961fc34e
Source dataset
uspto-grants-2013_08
Patent number
US08518944B2

Reaction notes

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