4-(3-Iodobenzyl)morpholine → (4-Methyl-pyridin-2-yl)-{6-[2-(3-morpholin-4-ylmethyl-phenyl)-oxazol-5-yl]-pyridin-2-yl}-amine hydrochloride

HRID 1854600Notes

Reaction equation

HRID 1854600 reaction equation
IC1C=C(C=CC=1)CN1CCCC1.[CH3:14][C:15]1[CH:20]=[CH:19][N:18]=[C:17]([NH:21][C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([C:28]3[O:32][C:31]([C:33]4[CH:38]=[CH:37][CH:36]=[C:35]([CH2:39][N:40]5[CH2:45][CH2:44][O:43][CH2:42][CH2:41]5)[CH:34]=4)=[N:30][CH:29]=3)[N:23]=2)[CH:16]=1.[ClH:46].CC1C=CN=C(NC2C=CC=C(C3OC(C4C=CC=C(CN5CCCC5)C=4)=NC=3)N=2)C=1.CC1C=CN=C(NC2C=CC=C(C3OC=NC=3)N=2)C=1.[I:97][C:98]1[CH:99]=[C:100]([CH:108]=[CH:109][CH:110]=1)[CH2:101][N:102]1[CH2:107][CH2:106][O:105][CH2:104][CH2:103]1.O(C(C)(C)C)[Li]>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>[I:97][C:98]1[CH:99]=[C:100]([CH:108]=[CH:109][CH:110]=1)[CH2:101][N:102]1[CH2:103][CH2:104][O:105][CH2:106][CH2:107]1.[ClH:46].[ClH:46].[CH3:14][C:15]1[CH:20]=[CH:19][N:18]=[C:17]([NH:21][C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([C:28]3[O:32][C:31]([C:33]4[CH:38]=[CH:37][CH:36]=[C:35]([CH2:39][N:40]5[CH2:45][CH2:44][O:43][CH2:42][CH2:41]5)[CH:34]=4)=[N:30][CH:29]=3)[N:23]=2)[CH:16]=1

Participants

11

Reactant 6

HCID 177503184-(3-Iodobenzyl)morpholineHCID 185258711-[(3-Iodophenyl)methyl]pyrrolidineHCID 53311228(4-Methyl-pyridin-2-yl)-(6-oxazol-5-yl-pyridin-2-yl)-amineHCID 67325008(4-Methyl-pyridin-2-yl)-{6-[2-(3-morpholin-4-ylmethyl-phenyl)-oxazol-5-yl]-pyridin-2-yl}-amineHCID 67325472(4-Methyl-pyridin-2-yl)-{6-[2-(3-pyrrolidin-1-ylmethyl-phenyl)-oxazol-5-yl]-pyridin-2-yl}-amine hydrochlorideHCID 178506942HCID 178506942, compound

Product 3

HCID 313Hydrochloric AcidHCID 177503184-(3-Iodobenzyl)morpholineHCID 67325007(4-Methyl-pyridin-2-yl)-{6-[2-(3-morpholin-4-ylmethyl-phenyl)-oxazol-5-yl]-pyridin-2-yl}-amine hydrochlorideYield 8%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

4-(3-Iodo-benzyl)-morpholine was prepared as described for 1-(3-iodo-benzyl)-pyrrolidine above. (4-Methyl-pyridin-2-yl)-{6-[2-(3-morpholin-4-ylmethyl-phenyl)-oxazol-5-yl]-pyridin-2-yl}-amine was then prepared as for (4-methyl-pyridin-2-yl)-{6-[2-(3-pyrrolidin-1-ylmethyl-phenyl)-oxazol-5-yl]-pyridin-2-yl}-amine hydrochloride above using (4-methyl-pyridin-2-yl)-(6-oxazol-5-yl-pyridin-2-yl)-amine (Example 008), 4-(3-iodo-benzyl)-morpholine, Pd(PPh3)4, LiOtBu and anhydrous 1,4-dioxane then HCl (2M in ether) to afford the title compound as a beige solid (8%). 1H NMR (400 MHz, DMSO-d6) δ 12.69-11.90 (m, 1H), 11.90-11.22 (m, 1H), 8.51 (s, 1H), 8.46 (d, J=5.8 Hz, 1H), 8.28 (s, 1H), 8.22 (d, J=7.7 Hz, 1H), 8.05 (t, J=7.9 Hz, 1H), 7.85 (d, J=7.5 Hz, 1H), 7.75 (d, J=7.7 Hz, 1H), 7.70 (t, J=7.7 Hz, 1H), 7.57 (s, 1H), 7.41 (d, J=8.3 Hz, 1H), 7.19 (d, J=4.5 Hz, 1H), 4.47 (s, 2H), 3.95 (d, J=11.8 Hz, 2H), 3.85 (t, J=11.8 Hz, 2H), 3.27 (d, J=11.8 Hz, 2H), 3.20-3.10 (m, 2H), 2.50 (s, 3H). (ESI+) m/z 428 (M+H)+. Retention time=1.80 mins (method 1).

Sources & evidence

ORD record
ord-31fa4b8b8108470399e89e2f112aa6f6
Source dataset
uspto-grants-2015_02
Patent number
US08962665B2

Reaction notes

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