Hydrochloric Acid → HCID 59671409, compound

HRID 1747638Notes

Reaction equation

HRID 1747638 reaction equation
[Si]([O:8][C@H:9]1[CH2:13][C@H:12]([O:14][C:15]2[C:20]([F:21])=[C:19]([NH:22][C@@H:23]3[C:31]4[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=4)[CH2:25][C@@H:24]3[O:32][CH3:33])[N:18]=[CH:17][N:16]=2)[CH2:11][C@H:10]1[CH2:34][OH:35])(C(C)(C)C)(C)C.C(N(CC)CC)C.C1(N(C2C=CC=CC=2)C([NH:52][S:53](Cl)(=[O:55])=[O:54])=O)C=CC=CC=1.Cl>C1COCC1>[S:53](=[O:55])(=[O:54])([O:35][CH2:34][C@@H:10]1[CH2:11][C@@H:12]([O:14][C:15]2[C:20]([F:21])=[C:19]([NH:22][C@@H:23]3[C:31]4[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=4)[CH2:25][C@@H:24]3[O:32][CH3:33])[N:18]=[CH:17][N:16]=2)[CH2:13][C@@H:9]1[OH:8])[NH2:52]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 66798152HCID 66798152, compoundHCID 86618726HCID 86618726, compound

Product 1

HCID 59671409HCID 59671409, compoundYield 54%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of {(1S,2S,4R)-2-{[tert-butyl(dimethyl)silyl]oxy}-4-[(5-fluoro-6-{[(1R,2S)-2-methoxy-2,3-dihydro-1H-inden-1-yl]amino}pyrimidin-4-yl)-oxy]cyclopentyl}methanol (190 mg, 0.36 mmol) in THF (5.40 mL) was added triethylamine (0.08 mL, 0.54 mmol) and [(diphenylamino)carbonyl]sulfamoyl chloride (186 mg, 0.54 mmol) at 0° C. under an atmosphere of Argon, and the mixture was stirred for 30 min. The reaction mixture was added 1.00 M Hydrochloric acid in (5.40 mL) at 23° C., and the resulting mixture was stirred for 16 h. The reaction mixture was quenched by addition of saturated NaHCO3 solution (80.0 mL) and extracted with ethyl acetate (3×100 mL). The organic layers were combined, dried over MgSO4, filtered, and evaporated under vacuum. The residue was purified via silica gel column chromatography eluting with a gradient of 0 to 10% methanol in DCM to afford the title compound (91.0 mg, 51%). 1H-NMR (400 MHz, CD3OD) δ: 8.01 (s, 1H), 7.25-7.13 (m, 4H), 5.72 (d, 1H, J=6.5 Hz), 5.65-5.58 (m, 1H), 4.43-4.38 (m, 1H), 4.33 (dd, 1H, J=9.7, 7.6 Hz), 4.22 (dt, 1H, J=5.0, 2.4 Hz), 4.16 (dd, 1H, J=9.7, 7.3 Hz), 3.35 (s, 3H), 3.14 (dd, 1H, J=16.6, 2.4 Hz), 3.02 (dd, 1H, J=16.6, 5.0 Hz), 2.60-2.49 (m, 1H), 2.31 (ddd, 1H, d=14.8, 6.8, 2.3 Hz), 2.12 (ddd, 1H, J=14.8, 5.0, 4.7), 2.08-1.95 (m, 2H). LC/MS: Rt=6.76, ES+ 469.3 (FA long).

Workup

  1. stirringthe resulting mixture was stirred for 16 h
  2. customThe reaction mixture was quenched by addition of saturated NaHCO3 solution (80.0 mL)
  3. extractionextracted with ethyl acetate (3×100 mL)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. customevaporated under vacuum
  7. customThe residue was purified via silica gel column chromatography
  8. washeluting with a gradient of 0 to 10% methanol in DCM

Sources & evidence

ORD record
ord-351fba9cd383436a9d08c8fdef3776c8
Source dataset
uspto-grants-2015_10
Patent number
US09150525B2

Reaction notes

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