Potassium Carbonate → HCID 89693930, compound

HRID 1504001Notes

Reaction equation

HRID 1504001 reaction equation
Cl.[OH:2][C@@H:3]([CH2:7][C@H:8]1[CH2:19][CH2:18][C:17]2[S:16][C:15]3[N:14]=[CH:13][N:12]=[C:11]([O:20][CH:21]4[CH2:26][CH2:25][CH:24]([NH:27][CH3:28])[CH2:23][CH2:22]4)[C:10]=3[C:9]1=2)[C:4]([NH2:6])=[O:5].C(=O)([O-])[O-].[K+].[K+].Cl[CH2:36][C:37]([N:39]1[CH2:43][CH2:42][CH2:41][CH2:40]1)=[O:38]>CN(C)C=O.O>[OH:2][C@@H:3]([CH2:7][C@H:8]1[CH2:19][CH2:18][C:17]2[S:16][C:15]3[N:14]=[CH:13][N:12]=[C:11]([O:20][CH:21]4[CH2:22][CH2:23][CH:24]([N:27]([CH3:28])[CH2:36][C:37](=[O:38])[N:39]5[CH2:43][CH2:42][CH2:41][CH2:40]5)[CH2:25][CH2:26]4)[C:10]=3[C:9]1=2)[C:4]([NH2:6])=[O:5]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 884401-(Chloroacetyl)pyrrolidineHCID 118567395HCID 118567395, compound

Product 1

HCID 89693930HCID 89693930, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

Into a 50-mL round-bottom flask, a solution of (2S)-2-hydroxy-3-[(3R)-12-[[4-(methylamino)cyclohexyl]oxy]-7-thia-9,11-diazatricyclo[6.4.0.0^[2,6]]dodeca-1(8),2(6),9,11-tetraen-3-yl]propanamide hydrochloride (110 mg, 0.26 mmol, 1.00 equiv), potassium carbonate (179 mg, 1.30 mmol, 5.03 equiv) and 2-chloro-1-(pyrrolidin-1-yl)ethan-1-one (152 mg, 1.03 mmol, 4.00 equiv) in N,N-dimethylformamide (6 mL) was stirred overnight at room temperature. The resulting solution was diluted with 20 mL of water. The resulting solution was extracted with 4×20 mL of ethyl acetate and the organic layers combined and concentrated under vacuum. The crude product was purified by flash preparative HPLC under the following conditions (IntelFlash-1): column: silica gel; mobile phase; Detector, UV 254 nm. This resulted in (2S)-2-hydroxy-3-[(3R)-12-[(4-[methyl[2-oxo-2-(pyrrolidin-1-yl)ethyl]amino]cyclohexyl)oxy]-7-thia-9,11-diazatricyclo[6.4.0.0^[2,6]]dodeca-1(8),2(6),9,11-tetraen-3-yl]propanamide (63.8 mg, 49%) as a white solid. 1H NMR (400 MHz, CD3OD): δ 8.47 (s, 1H), 5.28 (m, 1H), 4.17-4.14 (m, 1H), 3.59-3.32 (m, 7H), 3.15-2.98 (m, 2H), 2.76-2.70 (m, 2H), 2.52-2.33 (m, 7H), 2.04-1.89 (m, 6H), 1.74-1.53 (m, 5H). MS: m/z 502 (M+H)+.

Workup

  1. extractionThe resulting solution was extracted with 4×20 mL of ethyl acetate
  2. concentrationconcentrated under vacuum
  3. customThe crude product was purified by flash preparative HPLC under the following conditions (IntelFlash-1)
  4. customThis resulted in (2S)-2-hydroxy-3-[(3R)-12-[(4-[methyl[2-oxo-2-(pyrrolidin-1-yl)ethyl]amino]cyclohexyl)oxy]-7-thia-9,11-diazatricyclo[6.4.0.0^[2,6]]dodeca-1(8),2(6),9,11-tetraen-3-yl]propanamide (63.8 mg, 49%) as a white solid

Sources & evidence

ORD record
ord-8409e7a496264df6b2a3a4b8687bb8c2
Source dataset
uspto-grants-2015_12
Patent number
US09212190B2

Reaction notes

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