Dimethylformamide dimethyl acetal → 3-[4-(4-Methyl-2-morpholin-4-yl-thiazol-5-yl)-pyrimidin-2-ylamino]-phenol

HRID 599161Notes

Reaction equation

HRID 599161 reaction equation
[CH3:1][C:2]1[N:3]=[C:4]([N:10]2[CH2:15][CH2:14][O:13][CH2:12][CH2:11]2)[S:5][C:6]=1[C:7](=O)[CH3:8].Br[CH:17](C(=O)C)C(=O)C.COC(N(C)C)OC.[N+]([O-])(O)=O.[OH:36][C:37]1[CH:38]=[C:39]([NH:43][C:44]([NH2:46])=[NH:45])[CH:40]=[CH:41][CH:42]=1>>[CH3:1][C:2]1[N:3]=[C:4]([N:10]2[CH2:15][CH2:14][O:13][CH2:12][CH2:11]2)[S:5][C:6]=1[C:7]1[CH:8]=[CH:17][N:46]=[C:44]([NH:43][C:39]2[CH:38]=[C:37]([OH:36])[CH:42]=[CH:41][CH:40]=2)[N:45]=1

Participants

5

Reactant 4

HCID 78373Dimethylformamide dimethyl acetalHCID 3556413-Bromopentane-2,4-dioneHCID 27405521-(4-Methyl-2-morpholin-4-yl-1,3-thiazol-5-yl)ethanoneHCID 178512514HCID 178512514, compound

Product 1

HCID 100445943-[4-(4-Methyl-2-morpholin-4-yl-thiazol-5-yl)-pyrimidin-2-ylamino]-phenol

Procedure

A solution of morpholine-4-carbonitrile (10 g, 89.19 mmol) in EtOH (65 mL) was cooled on an ice bath. Anhydrous NH3 was bubbled through the solution for 5 min, followed by hydrogen sulfide. Soon after the introduction of H2S a white precipitate was observed. After the addition of both gases for 45 min NH3 addition was stopped and H2S continued for a further 15 minutes. The resulting precipitate was collected, washed with cold water, MeOH and dried under high vacuum to afford morpholine-4-carbothioic acid amide (12.83 g). Mp. 173-174° C. 1H-NMR (DMSO-D6) δ: 3.54 (t, 4H, J=4.9 Hz, CH2), 3.70 (m, 4H, CH2), 7.46 (brs, 2H, NH2). This was converted first to 1-(4-methyl-2-morpholin-4-yl-thiazol-5-yl)-ethanone with 3-bromo-pentane-2,4-dione, then with dimethoxymethyl-dimethyl-amine to 3-dimethylamino-1-(4-methyl-2-morpholin-4-yl-thiazol-5-yl)-propenone in the usual manner. The latter enaminone was condensed with N-(3-hydroxy-phenyl)-guanidine nitrate to afford the title compound as a. pale solid. Mp. 227-229 C. 1H-NMR (DMSO-D6) δ: 2.49 (s, 3H, CH3), 3.46 (t, 4H, J=4.4 Hz, CH2), 3.71 (t, 4H, J=4.4 Hz, pyrimidinyl-H), 6.34 (d, 1H, J=8.8 Hz, Ph-H), 6.91 (d, 1H, J=5.4 Hz, pyrimidinyl-H), 7.03 (t, 1H, J=7.8 Hz, Ph-H), 7.20-7.22 (m, 2H, Ph-H), 8.34 (d, 1H, J=5.4 Hz, pyrimidinyl-H), 9.17 (s, 1H, OH/NH), 9.32 (s, 1H, NH/OH). MS (ESI+) m/z 370.10 [M+H]+ (C18H19N5O2S requires 369.44).

Sources & evidence

ORD record
ord-30911e53375941a2ab8621a4b789f023
Source dataset
uspto-grants-2011_03
Patent number
US07897605B2

Reaction notes

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