4,4,4-Trifluorobutan-1-ol → US9777017, Example 60

HRID 712093Notes

Reaction equation

HRID 712093 reaction equation
[NH:1]1[CH2:6][CH2:5][CH:4]([N:7]2[C:11]3=[C:12]4[S:18][CH:17]=[CH:16][C:13]4=[N:14][CH:15]=[C:10]3[N:9]=[C:8]2[C@H:19]([OH:21])[CH3:20])[CH2:3][CH2:2]1.[F:22][C:23]([F:29])([F:28])[CH2:24][CH2:25][CH2:26]O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.C[N+](C)(C)C>C(Cl)Cl.CN(C)C=O>[F:22][C:23]([F:29])([F:28])[CH2:24][CH2:25][CH2:26][N:1]1[CH2:6][CH2:5][CH:4]([N:7]2[C:11]3=[C:12]4[S:18][CH:17]=[CH:16][C:13]4=[N:14][CH:15]=[C:10]3[N:9]=[C:8]2[C@H:19]([OH:21])[CH3:20])[CH2:3][CH2:2]1

Participants

6

Reactant 3

HCID 1363074,4,4-Trifluorobutan-1-olHCID 13696215Tetramethylammonium Triacetoxyborohydride (>90%)HCID 86717456(1R)-1-(1-piperidin-4-yl-1H-imidazo[4,5-d]thieno[3,2-b]pyridin-2-yl)ethanol

Product 1

HCID 73775083US9777017, Example 60Yield 34.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a mixture of (1R)-1-(1-piperidin-4-yl-1H-imidazo[4,5-d]thieno[3,2-b]pyridin-2-yl)ethanol (15.0 mg, 0.0496 mmol) and 4,4,4-trifluorobutanol (9.4 mg, 0.0744 mmol) in methylene chloride (0.3 mL) and N,N-dimethylformamide (0.2 mL) was added resin of tetramethylammonium triacetoxyborohydride (48.4 mg, 0.0992 mmol). The resulting mixture was stirred overnight. The mixture was filtered and concentrated then purified using RP-HPLC (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 30 mL/min) to give 7 mg (34%) of the desired product. LCMS calculated for C19H24F3N4OS (M+H)+: m/z=413.2. Found: 413.1. 1H NMR (300 MHz, CDCl3) δ 9.06 (s, 1H), 7.71-7.60 (m, 2H), 5.21 (s, 1H), 4.72-4.58 (m, 1H), 3.70-3.57 (m, 6H), 3.13 (d, J=9.8 Hz, 2H), 2.89-2.66 (m, 1H), 2.49 (t, J=6.9 Hz, 2H), 2.34-2.18 (m, 2H), 1.96 (s, 1H), 1.86-1.74 (m, 2H), 1.67 (s, 2H) ppm.

Workup

  1. filtrationThe mixture was filtered
  2. concentrationconcentrated
  3. customthen purified
  4. washeluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 30 mL/min)

Sources & evidence

ORD record
ord-da9f749b2e5f4350a275a925d1ac255e
Source dataset
uspto-grants-2015_11
Patent number
US09181271B2

Reaction notes

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