Acetic Acid → HCID 86762159, compound

HRID 1907420Notes

Reaction equation

HRID 1907420 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([F:25])=[C:6]([C@@:8]23[O:16][CH2:15][CH2:14][C@@H:13]2[CH2:12][S:11][C:10]([NH:17][C:18](=[O:24])[O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[N:9]3)[CH:7]=1.[C:26]1(=O)[CH2:30][CH2:29][CH2:28][CH2:27]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(=O)C>C1COCC1.O>[CH:26]1([NH:1][C:2]2[CH:3]=[CH:4][C:5]([F:25])=[C:6]([C@@:8]34[O:16][CH2:15][CH2:14][C@@H:13]3[CH2:12][S:11][C:10]([NH:17][C:18](=[O:24])[O:19][C:20]([CH3:21])([CH3:22])[CH3:23])=[N:9]4)[CH:7]=2)[CH2:30][CH2:29][CH2:28][CH2:27]1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 8452CyclopentanoneHCID 5049666Sodium triacetoxyborohydrideHCID 86762148HCID 86762148, compound

Product 1

HCID 86762159HCID 86762159, compoundYield 42.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of tert-butyl ((4aS,7aS)-7a-(5-amino-2-fluorophenyl)-4a,5,6,7a-tetrahydro-4H-furo[2,3-d][1,3]thiazin-2-yl)carbamate (Step D, Preparation 3, 32 mg, 0.087 mmol), cyclopentanone (23.38 μL, 0.261 mmol), sodium triacetoxyborohydride (55.4 mg, 0.261 mmol) and acetic acid (14.96 μL, 0.261 mmol) in THF (435 μL) was stirred at rt for 12 h, and LC/MS showed a very clean reaction. The crude reaction mixture was purified by reverse phase preparative HPLC on a Luna C18 column (10 μM, 30×100 mm) eluting with 0-100% B (A: 95% eater/5% MeCN/10 nM NH4OAc, B: 5% water/95% MeCN/10 mM NH4OAc) over 12 min to give tert-butyl ((4aS,7aS)-7a-(5-(cyclopentylamino)-2-fluorophenyl)-4a,5,6,7a-tetrahydro-4H-furo[2,3-d][1,3]thiazin-2-yl)carbamate (16 mg, 0.037 mmol, 42.2% yield) as a white solid. 1H NMR (500 MHz, CHLOROFORM-d) δ 6.90 (dd, J=11.1, 8.7 Hz, 1H), 6.74 (dd, J=6.4, 2.9 Hz, 1H), 6.51 (dt, J=8.7, 3.3 Hz, 1H), 4.22-4.14 (m, 1H), 4.04 (q, J=7.9 Hz, 1H), 3.74 (quin, J=6.1 Hz, 1H), 3.31 (dd, J=13.3, 3.1 Hz, 1H), 3.03 (br. s., 1H), 2.84 (dd, J=13.4, 4.3 Hz, 1H), 2.47-2.31 (m, 1H), 2.25-2.15 (m, 1H), 2.09-1.97 (m, 2H), 1.80-1.57 (m, 4H), 1.53-1.43 (m, 2H), and 1.50 (9H, s). MS (M+H)+: 436.3.

Workup

  1. customa very clean reaction
  2. customThe crude reaction mixture
  3. customwas purified by reverse phase preparative HPLC on a Luna C18 column (10 μM, 30×100 mm)
  4. washeluting with 0-100% B (A: 95% eater/5% MeCN/10 nM NH4OAc, B

Sources & evidence

ORD record
ord-90ba4578d5c74b119298a45c2679abdb
Source dataset
uspto-grants-2013_12
Patent number
US08598161B2

Reaction notes

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