Diisobutylaluminum hydride → N-(3-{2-[8-(aminomethyl)-1,4-dioxaspiro[4.5]dec-8-yl]-1,3-thiazol-5-yl}-5-methylphenyl)-4-(trifluoromethyl)pyrimidin-2-amine

HRID 410663Notes

Reaction equation

HRID 410663 reaction equation
[H-].C([Al+]CC(C)C)C(C)C.[CH3:11][C:12]1[CH:13]=[C:14]([C:29]2[S:33][C:32]([C:34]3([C:44]#[N:45])[CH2:43][CH2:42][C:37]4([O:41][CH2:40][CH2:39][O:38]4)[CH2:36][CH2:35]3)=[N:31][CH:30]=2)[CH:15]=[C:16]([NH:18][C:19]2[N:24]=[C:23]([C:25]([F:28])([F:27])[F:26])[CH:22]=[CH:21][N:20]=2)[CH:17]=1.CC(C[AlH]CC(C)C)C>>[NH2:45][CH2:44][C:34]1([C:32]2[S:33][C:29]([C:14]3[CH:15]=[C:16]([NH:18][C:19]4[N:24]=[C:23]([C:25]([F:26])([F:28])[F:27])[CH:22]=[CH:21][N:20]=4)[CH:17]=[C:12]([CH3:11])[CH:13]=3)=[CH:30][N:31]=2)[CH2:43][CH2:42][C:37]2([O:38][CH2:39][CH2:40][O:41]2)[CH2:36][CH2:35]1

Participants

4

Reactant 3

HCID 14487Diisobutylaluminum hydrideHCID 21225700DiisobutylaluminumhydrideHCID 672617008-[5-(3-Methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]-1,4-dioxaspiro[4.5]decane-8-carbonitrile

Product 1

HCID 67429575N-(3-{2-[8-(aminomethyl)-1,4-dioxaspiro[4.5]dec-8-yl]-1,3-thiazol-5-yl}-5-methylphenyl)-4-(trifluoromethyl)pyrimidin-2-amineYield 39%

Conditions

Temperature
-10 °C

Procedure

Diisobutylaluminum hydride (1M in Hexanes, 0.239 ml, 0.239 mmol, 1.2 equiv) was added to a solution of 8-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]-1,4-dioxaspiro[4.5]decane-8-carbonitrile (100 mg, 0.20 mmol) at −10° C. and the resulting cloudy mixture was stirred at −10° C. for 1 h. A second addition of DIBAL (1M in Hexanes, 0.239 ml, 0.239 mmol, 1.2 equiv) was made at −10° C. and the reaction was allowed to slowly warm to 23° C. and then stir for 4 days. The reaction was quenched with 1:1:3 mixture of water:aqueous 6N NaOH and the particulate matter was removed via filtration. The remaining filtrate was partitioned between EtOAc (2×55 ml) and water (65 ml). The combined organic layers were dried over Na2SO4, filtered and concentrated to afford N-(3-{2-[8-(aminomethyl)-1,4-dioxaspiro[4.5]dec-8-yl]-1,3-thiazol-5-yl}-5-methylphenyl)-4-(trifluoromethyl)pyrimidin-2-amine (39 mg, 39%), as an off-white solid. MS ESI: [M+H]+ m/z 506.1. 1H NMR (500 MHz, CDCl3) δ 8.66 (d, J=4.6 Hz, 1H), 7.93 (s, 1H), 7.45 (bs, 1H), 7.28 (s, 1H), 7.08-7.04 (m, 2H), 4.06-3.95 (m, 6H), 2.51-2.35 (m, 7H), 1.95-1.71 (m, 4H).

Workup

  1. customwas made at −10° C.
  2. temperatureto slowly warm to 23° C.
  3. stirringstir for 4 days
  4. customThe reaction was quenched with 1:1:3 mixture of water
  5. customaqueous 6N NaOH and the particulate matter was removed via filtration
  6. customThe remaining filtrate was partitioned between EtOAc (2×55 ml) and water (65 ml)
  7. dry with materialThe combined organic layers were dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-369ab262082a4a94ba11ca9a29598a8e
Source dataset
uspto-grants-2014_06
Patent number
US08759366B2

Reaction notes

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