Pivalic acid → HCID 178458935, compound

HRID 2272666Notes

Reaction equation

HRID 2272666 reaction equation
Br[C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:14]=[C:13]([CH:15]3[CH2:17][CH2:16]3)[CH:12]=[CH:11][N:10]=2)[CH:5]=[C:4]([CH3:18])[CH:3]=1.[OH:19][C:20]([C@H:28]1[CH2:33][CH2:32][C@H:31]([C:34]([O:36][CH3:37])=[O:35])[CH2:30][CH2:29]1)([C:23]1[S:24][CH:25]=[CH:26][N:27]=1)[CH2:21][CH3:22].C(O)(=O)C(C)(C)C.C(=O)([O-])[O-].[K+].[K+].C(P(C12CC3CC(CC(C3)C1)C2)C12CC3CC(CC(C3)C1)C2)CCC>C(OCC)C.CC(N(C)C)=O>[CH:15]1([C:13]2[CH:12]=[CH:11][N:10]=[C:9]([NH:8][C:6]3[N:7]=[C:2]([C:25]4[S:24][C:23]([C:20]([C@H:28]5[CH2:33][CH2:32][C@H:31]([C:34]([O:36][CH3:37])=[O:35])[CH2:30][CH2:29]5)([OH:19])[CH2:21][CH3:22])=[N:27][CH:26]=4)[CH:3]=[C:4]([CH3:18])[CH:5]=3)[CH:14]=2)[CH2:17][CH2:16]1

Participants

8

Reactant 5

HCID 6417Pivalic acidHCID 11430Potassium CarbonateHCID 11371790Bis(adamantan-1-yl)(butyl)phosphaneHCID 86715333HCID 86715333, compoundHCID 178458940HCID 178458940, compound

Product 1

HCID 178458935HCID 178458935, compound

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
100 °C

Procedure

6-Bromo-N-(4-cyclopropylpyridin-2-yl)-4-methylpyridin-2-amine (263 mg, 0.865 mmol), trans-methyl 4-[1-hydroxy-1-(1,3-thiazol-2-yl)propyl]cyclohexanecarboxylate (245 mg, 0.865 mmol), pivalic acid (151 μl, 1.297 mmol), potassium carbonate (358 mg, 2.59 mmol), π-allyl palladium(II)chloride dimer (31.6 mg, 0.086 mmol) and butyl di-1-adamantylphosphine (124 mg, 0.346 mmol) were combined and the reaction flask was put under inert atmosphere (3× vacuum/argon cycle) then degassed dimethylacetamide (2 mL) was added. The reaction was heated to 100° C. for 5 hours, then cooled to room temperature and poured into diethyl ether (100 mL). The resulting solution was transferred to a separatory funnel and sequentially washed with water (3×50 mL) and sodium bicarbonate (50 mL), dried over magnesium sulfate, filtered and concentrated under reduced pressure. The resulting crude oil was purified by silica gel chromatography (0-100% ethyl acetate/hexanes) to afford methyl trans-4-[l-(5-{6-[(4-cyclopropylpyridin-2-yl)amino]-4-methylpyridin-2-yl}-1,3-thiazol-2-yl)-1-hydroxypropyl]cyclohexanecarboxylate as a yellow foam. MS ESI calc'd. for C28H35N4O3S [M+H]+ 507. found 507. 1H NMR (500 MHz, CDCl3) δ 8.12-8.04 (m, 2H), 7.71 (s, 1H), 7.23 (s, 1H), 7.05 (s, 1H), 6.86 (s, 1H), 6.66 (d, J=5.2 Hz, 1H), 3.64 (s, 3H), 2.35 (s, 3H), 2.28-2.16 (m, 1H), 2.16-1.86 (m, 811), 1.51-1.30 (m, 3H), 1.26 (t, J=7.1 Hz, 1H), 1.21-1.06 (m, 3H), 1.03-0.93 (m, 2H), 0.83 (t, J=7.2 Hz, 3H).

Workup

  1. temperaturecooled to room temperature
  2. customThe resulting solution was transferred to a separatory funnel
  3. washsequentially washed with water (3×50 mL) and sodium bicarbonate (50 mL)
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe resulting crude oil was purified by silica gel chromatography (0-100% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-37dae223e39844b28028232b628570ed
Source dataset
uspto-grants-2015_09
Patent number
US09120785B2

Reaction notes

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