Hydrochloric Acid → (4-Methyl-pyridin-2-yl)-{6-[2-(3-pyrrolidin-1-ylmethyl-phenyl)-oxazol-5-yl]-pyridin-2-yl}-amine hydrochloride

HRID 1854599Notes

Reaction equation

HRID 1854599 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([NH:8][C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([C:15]3[O:19][C:18]([C:20]4[CH:25]=[CH:24][CH:23]=[C:22]([CH2:26][N:27]5[CH2:31][CH2:30][CH2:29][CH2:28]5)[CH:21]=4)=[N:17][CH:16]=3)[N:10]=2)[CH:3]=1.CC1C=CN=C(NC2N=C(C3OC(C=CC4C=CC(C#N)=CC=4)=NC=3)C=CC=2)C=1.CC1C=CN=C(NC2C=CC=C(C3OC=NC=3)N=2)C=1.IC1C=C(C=CC=1)CN1CCCC1.O(C(C)(C)C)[Li].[ClH:99]>CCOC(C)=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O1CCOCC1>[ClH:99].[CH3:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([NH:8][C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([C:15]3[O:19][C:18]([C:20]4[CH:25]=[CH:24][CH:23]=[C:22]([CH2:26][N:27]5[CH2:31][CH2:30][CH2:29][CH2:28]5)[CH:21]=4)=[N:17][CH:16]=3)[N:10]=2)[CH:3]=1

Participants

10

Reactant 6

HCID 313Hydrochloric AcidHCID 185258711-[(3-Iodophenyl)methyl]pyrrolidineHCID 53311228(4-Methyl-pyridin-2-yl)-(6-oxazol-5-yl-pyridin-2-yl)-amineHCID 673240684-(2-{5-[6-(4-Methyl-pyridin-2-ylamino)-pyridin-2-yl]-oxazol-2-yl}-vinyl)-benzonitrileHCID 67324507(4-Methyl-pyridin-2-yl)-{6-[2-(3-pyrrolidin-1-ylmethyl-phenyl)-oxazol-5-yl]-pyridin-2-yl}-amineHCID 178506942HCID 178506942, compound

Product 1

HCID 67325472(4-Methyl-pyridin-2-yl)-{6-[2-(3-pyrrolidin-1-ylmethyl-phenyl)-oxazol-5-yl]-pyridin-2-yl}-amine hydrochlorideYield 35%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

(4-Methyl-pyridin-2-yl)-{6-[2-(3-pyrrolidin-1-ylmethyl-phenyl)-oxazol-5-yl]-pyridin-2-yl}-amine was then prepared as for 4-(2-{5-[6-(4-methyl-pyridin-2-ylamino)-pyridin-2-yl]-oxazol-2-yl}-vinyl)-benzonitrile above using (4-methyl-pyridin-2-yl)-(6-oxazol-5-yl-pyridin-2-yl)-amine (Example 008), 1-(3-iodo-benzyl)-pyrrolidine, Pd(PPh3)4, LiOtBu and anhydrous 1,4-dioxane. The isolated material was taken up in EtOAc and treated with HCl (2M in ether) to afford the title compound as a beige solid (35%) after evaporation under vacuum. 1H NMR (400 MHz, DMSO-d6) δ 12.65 (s, 1H), 11.30 (s, 1H), 8.53-8.47 (m, 2H), 8.33 (s, 1H), 8.19 (d, J=7.6 Hz, 1H), 8.07 (t, J=7.9 Hz, 1H), 7.85 (d, J=7.8 Hz, 1H), 7.80 (d, J=7.6 Hz, 1H), 7.67 (t, J=7.7 Hz, 1H), 7.52 (s, 1H), 7.38 (d, J=8.3 Hz, 1H), 7.24 (d, J=6.4 Hz, 1H), 4.48 (d, J=5.6 Hz, 2H), 3.42-3.29 (m, 4H), 2.51 (s, 3H), 2.09-1.86 (m, 4H). (ESI+) m/z 412 (M+H)+. Retention time=1.88 mins (method 1).

Sources & evidence

ORD record
ord-e21a9d3633d54210a4fb24974ddf084b
Source dataset
uspto-grants-2015_02
Patent number
US08962665B2

Reaction notes

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