Hydrochloric Acid → HCID 68115483, compound

HRID 1503965Notes

Reaction equation

HRID 1503965 reaction equation
[Si]([O:8][CH:9]([CH2:13][C@H:14]1[CH2:25][CH2:24][C:23]2[S:22][C:21]3[N:20]=[CH:19][N:18]=[C:17]([O:26][CH:27]4[CH2:32][CH2:31][CH:30]([N:33]5[CH2:38][CH2:37][O:36][CH2:35][CH2:34]5)[CH2:29][CH2:28]4)[C:16]=3[C:15]1=2)[C:10]([NH2:12])=[O:11])(C(C)(C)C)(C)C.Cl>CO>[OH:8][CH:9]([CH2:13][C@H:14]1[CH2:25][CH2:24][C:23]2[S:22][C:21]3[N:20]=[CH:19][N:18]=[C:17]([O:26][CH:27]4[CH2:28][CH2:29][CH:30]([N:33]5[CH2:38][CH2:37][O:36][CH2:35][CH2:34]5)[CH2:31][CH2:32]4)[C:16]=3[C:15]1=2)[C:10]([NH2:12])=[O:11]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 86695133HCID 86695133, compound

Product 1

HCID 68115483HCID 68115483, compoundYield 79.3%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A 100-mL round-bottom flask was charged with a solution of 2-[(tert-butyldimethylsilyl)oxy]-3-[(3R)-12-[[4-(morpholin-4-yl)cyclohexyl]oxy]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2 (6),9,11-tetraen-3-yl]propanamide (197 mg, 0.35 mmol, 1.00 equiv) in methanol (10 mL). Hydrochloric acid (2 M, 0.8 mL) was added and stirring continued for 2 hr in a water/ice bath. After completion, the reaction was quenched with saturated aqueous sodium bicarbonate and extracted with 3×30 mL of DCM. The organic phase was dried over sodium sulfate and concentrated under vacuum. The residue was purified by preparative TLC (DCM/MeOH:10/1) to afford the 2-hydroxy-3-[(3R)-12-[[4-(morpholin-4-yl)cyclohexyl]oxy]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2 (6),9,11-tetraen-3-yl]propanamide (124 mg, 79%) as a white solid. MS (ES): m/z 447 [M+H]+. 1H NMR (400 MHz, CDCl3): δ 8.46 (s, 1H), 5.28-5.25 (m, 1H), 4.17-4.06 (m, 51H), 3.74-3.72 (m, 5H), 3.37-2.98 (m, 2H), 2.72-2.28 (m, 10H), 2.11-2.08 (m, 2H), 1.79-1.46 (m, 5H).

Workup

  1. customAfter completion, the reaction was quenched with saturated aqueous sodium bicarbonate
  2. extractionextracted with 3×30 mL of DCM
  3. dry with materialThe organic phase was dried over sodium sulfate
  4. concentrationconcentrated under vacuum
  5. customThe residue was purified by preparative TLC (DCM/MeOH:10/1)

Sources & evidence

ORD record
ord-e4a8349fda6c4585bf958ae9e8c627be
Source dataset
uspto-grants-2015_12
Patent number
US09212190B2

Reaction notes

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