1,4-Dioxaspiro[4.5]decan-8-one → N-(1-(4-hydroxy-4-(isothiazol-5-yl)cyclohexyl)azetidin-3-yl)-2-((6-(trifluoromethyl)quinazolin-4-yl)amino)acetamide

HRID 2175587Notes

Reaction equation

HRID 2175587 reaction equation
[OH:1][C:2]1([C:9]2[S:13][N:12]=[CH:11][CH:10]=2)[CH2:7][CH2:6][C:5](=O)[CH2:4][CH2:3]1.BrC1SN=CC=1.O1C2(CCC(=O)CC2)OCC1.[NH:31]1[CH2:34][CH:33]([NH:35][C:36](=[O:53])[CH2:37][NH:38][C:39]2[C:48]3[C:43](=[CH:44][CH:45]=[C:46]([C:49]([F:52])([F:51])[F:50])[CH:47]=3)[N:42]=[CH:41][N:40]=2)[CH2:32]1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>>[OH:1][C:2]1([C:9]2[S:13][N:12]=[CH:11][CH:10]=2)[CH2:7][CH2:6][CH:5]([N:31]2[CH2:32][CH:33]([NH:35][C:36](=[O:53])[CH2:37][NH:38][C:39]3[C:48]4[C:43](=[CH:44][CH:45]=[C:46]([C:49]([F:50])([F:52])[F:51])[CH:47]=4)[N:42]=[CH:41][N:40]=3)[CH2:34]2)[CH2:4][CH2:3]1

Participants

6

Reactant 5

HCID 5674151,4-Dioxaspiro[4.5]decan-8-oneHCID 5049666Sodium triacetoxyborohydrideHCID 126311745-Bromo-1,2-thiazoleHCID 593615564-Hydroxy-4-isothiazol-5-yl-cyclohexanoneHCID 68003594N-(azetidin-3-yl)-2((6-(trifluoromethyl)quinazolin-4-yl)amino)acetamide

Product 1

HCID 68003782N-(1-(4-hydroxy-4-(isothiazol-5-yl)cyclohexyl)azetidin-3-yl)-2-((6-(trifluoromethyl)quinazolin-4-yl)amino)acetamide

Procedure

Reaction of 4-hydroxy-4-(isothiazol-5-yl)cyclohexanone (prepared by the reaction of 5-bromoisothiazole with 1,4-dioxaspiro[4.5]decan-8-one using the sequence described in Example 24 Step A-B) 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 (CHLOROFORM-d) δ: 8.61 (s, 1 H), 8.45-8.51 (m, 1 H), 8.35 (d, J=1.8 Hz, 1 H), 7.92-7.98 (m, 1 H), 7.87-7.92 (m, 1 H), 7.04 (d, J=1.8 Hz, 1 H), 4.62 (t, J=6.8 Hz, 1 H), 4.21-4.31 (m, 2 H), 3.97-4.09 (m, 2 H), 3.79-3.88 (m, 1 H), 3.13 (q, J=7.3 Hz, 6 H), 2.05-2.26 (m, 2 H), 1.78 (d, J=12.9 Hz, 6 H), 1.35 (t, J=7.3 Hz, 9 H); ESI-MS (m/z): Calcd. For C23H25F3N6O2S: 506.17. found: 507 (M+H).

Workup

  1. customafforded the product

Sources & evidence

ORD record
ord-d867062daa1b4cd489b8391fd5e066ab
Source dataset
uspto-grants-2015_06
Patent number
US09062048B2

Reaction notes

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