Acetic Acid → HCID 178441316, compound

HRID 78552

Reaction equation

HRID 78552 reaction equation
[C:1]([C:5]1[S:9]/[C:8](=[N:10]\[C:11](=[O:24])[C:12]2[CH:17]=[C:16]([C:18]([F:21])([F:20])[F:19])[CH:15]=[CH:14][C:13]=2[CH:22]=O)/[N:7]([CH2:25][C@H:26]2[CH2:30][CH2:29][CH2:28][O:27]2)[CH:6]=1)([CH3:4])([CH3:3])[CH3:2].C([BH3-])#N.[NH:34]1[CH2:38][CH2:37][CH2:36][C@H:35]1[CH2:39][OH:40].C(O)(=O)C>ClCCl.CO>[C:1]([C:5]1[S:9]/[C:8](=[N:10]\[C:11](=[O:24])[C:12]2[CH:17]=[C:16]([C:18]([F:21])([F:19])[F:20])[CH:15]=[CH:14][C:13]=2[CH2:22][N:34]2[CH2:38][CH2:37][CH2:36][C@H:35]2[CH2:39][OH:40])/[N:7]([CH2:25][C@H:26]2[CH2:30][CH2:29][CH2:28][O:27]2)[CH:6]=1)([CH3:3])([CH3:4])[CH3:2]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 498716Cyano-borohydrideHCID 640091L-ProlinolHCID 178441317HCID 178441317, compound

Product 1

HCID 178441316HCID 178441316, compoundYield 38%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

In a vial (5 mL), a mixture of Example 375C (88 mg, 0.200 mmol), support-bound cyanoborohydride resin (0.256 g, 0.599 mmol), (S)-pyrrolidin-2-ylmethanol (60 mg, 0.593 mmol), and acetic acid (18 mg, 0.300 mmol) in dichloromethane (1 mL) and methyl alcohol (1 mL) was shaken on an orbit shaker for 2 hr. The reaction was filtered, concentrated and the residue was purified by preparative HPLC on a Phenomenex Luna Combi-HTS C8(2) column (5 μm, 100 Å, 2.1 mm×30 mm), using a gradient of 10-100% acetonitrile (A) and 0.1% trifluoroacetic acid in water (B), at a flow rate of 2.0 mL/min (0-0.1 min 10% A, 0.1-2.6 min 10-100% A, 2.6-2.9 min 100% A, 2.9-3.0 min 100-10% A. 0.5 min post-run delay) in 38% yield as TFA salt. 1H NMR (300 MHz, CD3OD) δ ppm 1.41 (s, 9H) 1.72-1.81 (m, 1H) 1.88-1.99 (m, 2H) 2.05-2.20 (m, 3H) 2.27-2.41 (m, 1H) 3.34-3.42 (m, 1H) 3.52-3.66 (m, 1H) 3.67-3.82 (m, 4H) 3.85-3.96 (m, 1H) 4.36-4.46 (m, 3H) 4.57 (d, J=12.69 Hz, 1H) 4.86-4.93 (m, 2H) 7.28 (s, 1H) 7.76-7.82 (m, 1H) 7.87-7.94 (m, 1H) 8.73-8.75 (m, 1H); MS (DCI/NH3) m/z 526 (M+H)+. Anal. calcd calcd C26H34F3N3O3S.1.9 CF3CO2H: C, 48.22; H, 4.87; N, 5.66. Found: C, 48.28; H, 4.63; N, 5.67.

Workup

  1. filtrationThe reaction was filtered
  2. concentrationconcentrated
  3. customthe residue was purified by preparative HPLC on a Phenomenex Luna Combi-HTS C8(2) column (5 μm, 100 Å, 2.1 mm×30 mm)
  4. customat a flow rate of 2.0 mL/min (0-0.1 min 10% A, 0.1-2.6 min 10-100% A, 2.6-2.9 min 100% A, 2.9-3.0 min 100-10% A. 0.5 min post-run delay)

Sources & evidence

ORD record
ord-c0f139499e534863bcc5a1fc2f7db902
Source dataset
uspto-grants-2014_09
Patent number
US08841334B2

Linked notes

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