Sodium cyanoborohydride → {3-(4-{[4-({[tert-Butyl(diphenyl)silyl]oxy}methyl)-6-(trifluoromethyl)pyridin-2-yl]oxy}piperidin-1-yl)-1-[4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]cyclobutyl}acetonitrile

HRID 1426340ノート

反応式

HRID 1426340 の反応式
C([BH3-])#N.[Na+].O=[C:6]1[CH2:9][C:8]([CH2:32][C:33]#[N:34])([N:10]2[CH:14]=[C:13]([C:15]3[C:16]4[CH:23]=[CH:22][N:21]([CH2:24][O:25][CH2:26][CH2:27][Si:28]([CH3:31])([CH3:30])[CH3:29])[C:17]=4[N:18]=[CH:19][N:20]=3)[CH:12]=[N:11]2)[CH2:7]1.[Si:35]([O:52][CH2:53][C:54]1[CH:59]=[C:58]([C:60]([F:63])([F:62])[F:61])[N:57]=[C:56]([O:64][CH:65]2[CH2:70][CH2:69][NH:68][CH2:67][CH2:66]2)[CH:55]=1)([C:48]([CH3:51])([CH3:50])[CH3:49])([C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1)[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1>CO.CCOC(C)=O.[Cl-].[Cl-].[Zn+2].[BH3-]C#N.[Na+].[Cl-].[Cl-].[Zn+2]>[Si:35]([O:52][CH2:53][C:54]1[CH:59]=[C:58]([C:60]([F:63])([F:62])[F:61])[N:57]=[C:56]([O:64][CH:65]2[CH2:66][CH2:67][N:68]([CH:6]3[CH2:7][C:8]([CH2:32][C:33]#[N:34])([N:10]4[CH:14]=[C:13]([C:15]5[C:16]6[CH:23]=[CH:22][N:21]([CH2:24][O:25][CH2:26][CH2:27][Si:28]([CH3:30])([CH3:29])[CH3:31])[C:17]=6[N:18]=[CH:19][N:20]=5)[CH:12]=[N:11]4)[CH2:9]3)[CH2:69][CH2:70]2)[CH:55]=1)([C:48]([CH3:50])([CH3:49])[CH3:51])([C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)[C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1

参加物

8

反応物 3

HCID 5003444Sodium cyanoborohydrideHCID 696736304-({[tert-Butyl(diphenyl)silyl]oxy}methyl)-2-(piperidin-4-yloxy)-6-(trifluoromethyl)pyridineHCID 69675509{3-oxo-1-[4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]cyclobutyl}acetonitrile

生成物 1

HCID 86666504{3-(4-{[4-({[tert-Butyl(diphenyl)silyl]oxy}methyl)-6-(trifluoromethyl)pyridin-2-yl]oxy}piperidin-1-yl)-1-[4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]cyclobutyl}acetonitrile

試薬・触媒・溶媒 4

HCID 3007855Zincchloride触媒HCID 131717307ZINC chloride sodium cyanoborohydride触媒HCID 887Methanol溶媒2 回HCID 8857Ethyl Acetate溶媒

実験手順

Sodium cyanoborohydride (8.8 mg, 0.14 mmol) and zinc dichloride (9.5 mg, 0.070 mmol) were combined in methanol (0.56 mL, 14 mmol) and stirred for 2 hours to generate the reducing solution referenced in JOC 1985, 50, 1927-1932. Subsequently, {3-oxo-1-[4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]cyclobutyl}acetonitrile (66 mg, 0.14 mmol, from Step 7 of Example 1a) and 4-({[tert-butyl(diphenyl)silyl]oxy}methyl)-2-(piperidin-4-yloxy)-6-(trifluoromethyl)pyridine (60. mg, 0.12 mmol, from Step C) were combined in Methanol (2.0 mL) to dissolve, then the above generated reducing mixture was added. The reaction was stirred overnight. An additional 0.3 eq of the prestirred NaCNBH3/ZnCl2 mixture was added. After stirring for 3 hours, the mixture was diluted with EtOAc and was washed with saturated sodium bicarbonate solution, followed by brine, dried over sodium sulfate, filtered and concentrated. Flash chromatography on silica gel, eluting with a gradient from 0-80% EtOAc in hexanes afforded product as a mixture of cis- and trans-isomers (43 mg, 40%). LCMS (M+2H)2+: 461.4.

後処理

  1. dissolutionto dissolve
  2. additionwas added
  3. stirringThe reaction was stirred overnight
  4. stirringAfter stirring for 3 hours
  5. washwas washed with saturated sodium bicarbonate solution
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. washFlash chromatography on silica gel, eluting with a gradient from 0-80% EtOAc in hexanes afforded product as a mixture of cis- and trans-isomers (43 mg, 40%)

出典と根拠

ORDレコード
ord-2b8a5fee059744a6a07bc4b41e82df3b
出典データセット
uspto-grants-2015_01
特許番号
US08933085B2

反応ノート

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