Sodium triacetoxyborohydride → HCID 178504212, compound

HRID 2200817Notes

Reaction equation

HRID 2200817 reaction equation
Cl.Cl.C[Si](C)(C)CCOCN1C2N=CN=C(C3C=NN(C4(CC#N)CNC4)C=3)C=2C=C1.OCC1C=C(C(F)(F)F)N=C(OC2CCC(=O)CC2)C=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[OH:66][CH2:67][C:68]1[CH:73]=[C:72]([C:74]([F:77])([F:76])[F:75])[N:71]=[C:70]([O:78][C@H:79]2[CH2:84][CH2:83][C@H:82]([N:85]3[CH2:88][C:87]([CH2:111][C:112]#[N:113])([N:89]4[CH:93]=[C:92]([C:94]5[C:95]6[CH:102]=[CH:101][N:100]([CH2:103][O:104][CH2:105][CH2:106][Si:107]([CH3:110])([CH3:109])[CH3:108])[C:96]=6[N:97]=[CH:98][N:99]=5)[CH:91]=[N:90]4)[CH2:86]3)[CH2:81][CH2:80]2)[CH:69]=1>ClCCCl>[OH:66][CH2:67][C:68]1[CH:73]=[C:72]([C:74]([F:75])([F:77])[F:76])[N:71]=[C:70]([O:78][C@@H:79]2[CH2:80][CH2:81][C@H:82]([N:85]3[CH2:86][C:87]([CH2:111][C:112]#[N:113])([N:89]4[CH:93]=[C:92]([C:94]5[C:95]6[CH:102]=[CH:101][N:100]([CH2:103][O:104][CH2:105][CH2:106][Si:107]([CH3:108])([CH3:109])[CH3:110])[C:96]=6[N:97]=[CH:98][N:99]=5)[CH:91]=[N:90]4)[CH2:88]3)[CH2:83][CH2:84]2)[CH:69]=1

Participants

6

Reactant 4

HCID 5049666Sodium triacetoxyborohydrideHCID 67391464{3-[4-(7-{[2-(Trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile dihydrochlorideHCID 71257695HCID 71257695, compoundHCID 178504213HCID 178504213, compound

Product 1

HCID 178504212HCID 178504212, compound

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

{3-[4-(7-{[2-(Trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile dihydrochloride (400.0 mg, 0.829 mmol) and 4-{[4-(hydroxymethyl)-6-(trifluoromethyl)pyridin-2-yl]oxy}cyclohexanone (300.0 mg, 1.037 mmol) were mixed in dry 1,2-dichloroethane (11.33 mL) and were stirred for 5 minutes. Sodium triacetoxyborohydride (708 mg, 3.34 mmol) was added to this mixture. The reaction mixture was stirred at 25 C for 16 hours, at which time LCMS analysis showed mainly the two diastereomeric products. The reaction was quenched with water, neutralized with NaHCO3 and extracted with ethyl acetate and the solvent was evaporated. The residue was purified by LCMS (pH 10) and the fractions containing the second peak were combined and evaporated to give 1-(cis-4-{[4-(hydroxymethyl)-6-(trifluoromethyl)pyridin-2-yl]oxy}cyclohexyl)-3-[4-(7-{[2-(trimethyl silyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile. MS (ES): 683 (M+1). The first peak contained {1-(trans-4-{[4-(hydroxymethyl)-6-(trifluoromethyl)pyridin-2-yl]oxy}cyclohexyl)-3-[4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile. MS (ES): 683 (M+1).

Workup

  1. stirringThe reaction mixture was stirred at 25 C for 16 hours, at which time LCMS analysis
  2. customThe reaction was quenched with water
  3. extractionextracted with ethyl acetate
  4. customthe solvent was evaporated
  5. customThe residue was purified by LCMS (pH 10)
  6. additionthe fractions containing the second peak
  7. customevaporated
  8. customto give 1-(cis-4-{[4-(hydroxymethyl)-6-(trifluoromethyl)pyridin-2-yl]oxy}cyclohexyl)-3-[4-(7-{[2-(trimethyl silyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile

Sources & evidence

ORD record
ord-734977e33c7b4ffdb417a47d7be4ee54
Source dataset
uspto-grants-2016_06
Patent number
US09359358B2

Reaction notes

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