Water → tert-butyl ((1S,4S)-4-(2-hydroxyethyl)-4-(3-(trifluoromethyl)-5,6,7,8-tetrahydro-1,6-naphthyridine-6-carbonyl)cyclopent-2-en-1-yl)carbamate

HRID 1747120Notes

Reaction equation

HRID 1747120 reaction equation
[Si]([O:8][CH2:9][CH2:10][C@@:11]1([C:24]([N:26]2[CH2:35][CH2:34][C:33]3[N:32]=[CH:31][C:30]([C:36]([F:39])([F:38])[F:37])=[CH:29][C:28]=3[CH2:27]2)=[O:25])[CH2:15][C@H:14]([NH:16][C:17](=[O:23])[O:18][C:19]([CH3:22])([CH3:21])[CH3:20])[CH:13]=[CH:12]1)(C(C)(C)C)(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-].O>C1COCC1>[OH:8][CH2:9][CH2:10][C@@:11]1([C:24]([N:26]2[CH2:35][CH2:34][C:33]3[N:32]=[CH:31][C:30]([C:36]([F:39])([F:38])[F:37])=[CH:29][C:28]=3[CH2:27]2)=[O:25])[CH2:15][C@H:14]([NH:16][C:17](=[O:23])[O:18][C:19]([CH3:22])([CH3:21])[CH3:20])[CH:13]=[CH:12]1

Participants

5

Reactant 3

HCID 962WaterHCID 2724141Tetrabutylammonium FluorideHCID 86708130tert-butyl ((1S,4S)-4-(2-((tert-butyldimethylsilyl)oxy)ethyl)-4-(3-(trifluoromethyl)-5,6,7,8-tetrahydro-1,6-naphthyridine-6-carbonyl)cyclopent-2-en-1-yl)carbamate

Product 1

HCID 86708129tert-butyl ((1S,4S)-4-(2-hydroxyethyl)-4-(3-(trifluoromethyl)-5,6,7,8-tetrahydro-1,6-naphthyridine-6-carbonyl)cyclopent-2-en-1-yl)carbamate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of the product of Step C (3.52 g, 6.18 mmol, 1 eq) in THF (50 mL) at rt was added TBAF in THF (12.36 mL of a 1 M solution, 12.36 mmol, 2 eq). After 1 hr, water was added, the solution extracted with DCM, the organics combined, dried over MgSO4, and concentrated. Purification by chromatography (80 g column) eluting with 2 to 6% methanol/DCM with ammonia afforded the title compound of Step D. 1H NMR (CHLOROFORM-d) δ: 8.71 (s, 1H), 7.70 (s, 1H), 6.28 (dd, J=5.9, 2.0 Hz, 1H), 5.78 (dd, J=5.9, 2.0 Hz, 1H), 4.70-4.95 (m, 4H), 3.99-4.10 (m, 1H), 3.85-3.96 (m, 1H), 3.68 (br. s., 2H), 3.09-3.18 (m, 2H), 2.65 (dd, J=12.9, 7.4 Hz, 1H), 1.99-2.21 (m, 3H), 1.82-1.93 (m, 1H), 1.38-1.49 (m, 9H). Calculated for C22H28F3N3O4: 456.2 (M+1). found: 456.2.

Workup

  1. extractionthe solution extracted with DCM
  2. dry with materialdried over MgSO4
  3. concentrationconcentrated
  4. customPurification by chromatography (80 g column)
  5. washeluting with 2 to 6% methanol/DCM with ammonia

Sources & evidence

ORD record
ord-99ba8a257023426080f7194658abd1a6
Source dataset
uspto-grants-2015_10
Patent number
US09150532B2

Reaction notes

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