3-Bromopyridine → N-(1-(4-(pyridin-3-yl)cyclohexyl)azetidin-3-yl)-2-((6-(trifluoromethyl)quinazolin-4-yl)amino)acetamide

HRID 2175576Notes

Reaction equation

HRID 2175576 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([CH:7]2[CH2:12][CH2:11][C:10](=O)[CH2:9][CH2:8]2)[CH:2]=1.BrC1C=NC=CC=1.CC1(C)C(C)(C)OB(C2CCC3(OCCO3)CC=2)O1.[NH:40]1[CH2:43][CH:42]([NH:44][C:45](=[O:62])[CH2:46][NH:47][C:48]2[C:57]3[C:52](=[CH:53][CH:54]=[C:55]([C:58]([F:61])([F:60])[F:59])[CH:56]=3)[N:51]=[CH:50][N:49]=2)[CH2:41]1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>>[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([CH:7]2[CH2:12][CH2:11][CH:10]([N:40]3[CH2:41][CH:42]([NH:44][C:45](=[O:62])[CH2:46][NH:47][C:48]4[C:57]5[C:52](=[CH:53][CH:54]=[C:55]([C:58]([F:59])([F:61])[F:60])[CH:56]=5)[N:51]=[CH:50][N:49]=4)[CH2:43]3)[CH2:9][CH2:8]2)[CH:2]=1

Participants

6

Reactant 5

HCID 122863-BromopyridineHCID 36970768-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1,4-dioxaspiro(4.5)dec-7-eneHCID 5049666Sodium triacetoxyborohydrideHCID 200349074-(Pyridin-3-yl)cyclohexan-1-oneHCID 68003594N-(azetidin-3-yl)-2((6-(trifluoromethyl)quinazolin-4-yl)amino)acetamide

Product 1

HCID 54772203N-(1-(4-(pyridin-3-yl)cyclohexyl)azetidin-3-yl)-2-((6-(trifluoromethyl)quinazolin-4-yl)amino)acetamide

Procedure

Reaction of 4-(pyridin-3-yl)cyclohexanone (prepared by the reaction of 3-bromopyridine with 8-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-1,4-dioxa-spiro[4.5]dec-7-ene using the sequence described in Example 1 Step A-C) with N-(azetidin-3-yl)-2-((6-(trifluoromethyl)quinazolin-4-yl)amino)acetamide (as prepared in Example 1 Step G) in the presence of TEA and NaBH(OAc)3 as described in Example 1, Step H afforded the product. 1H NMR (MeOD) δ: 8.62 (s, 1 H), 8.56 (s, 1 H), 8.43 (d, J=2.0 Hz, 1 H), 8.33 (dd, J=5.1, 1.5 Hz, 1 H), 8.04 (dd, J=8.8, 1.8 Hz, 1 H), 7.88 (d, J=8.8 Hz, 1 H), 7.77 (dt, J=7.8, 1.8 Hz, 1 H), 7.35 (dd, J=7.7, 5.2 Hz, 1 H), 4.51 (quin, J=7.1 Hz, 1 H), 4.28 (s, 2 H), 3.65-3.73 (m, 2 H), 2.95 (t, J=7.6 Hz, 2 H), 2.56-2.69 (m, 1 H), 2.43 (d, J=2.8 Hz, 1 H), 1.68-1.92 (m, 4 H), 1.49-1.62 (m, 4 H); ESI-MS (m/z): Calcd. For C25H27F3N6O: 484.22. found: 485 (M+H).

Workup

  1. customafforded the product

Sources & evidence

ORD record
ord-5a832d9777c04de497565e0d4a08690c
Source dataset
uspto-grants-2015_06
Patent number
US09062048B2

Reaction notes

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