Hydrochloric Acid → HCID 86695206, compound

HRID 1504048Notes

Reaction equation

HRID 1504048 reaction equation
[C:1]([CH2:4][C@H:5]1[CH2:16][CH2:15][C:14]2[S:13][C:12]3[N:11]=[CH:10][N:9]=[C:8]([O:17][CH:18]4[CH2:23][CH2:22][C:21]([NH:25]C(=O)OC(C)(C)C)([CH3:24])[CH2:20][CH2:19]4)[C:7]=3[C:6]1=2)(=[O:3])[NH2:2].Cl>ClCCl>[NH2:25][C:21]1([CH3:24])[CH2:20][CH2:19][CH:18]([O:17][C:8]2[C:7]3[C:6]4[C@@H:5]([CH2:4][C:1]([NH2:2])=[O:3])[CH2:16][CH2:15][C:14]=4[S:13][C:12]=3[N:11]=[CH:10][N:9]=2)[CH2:23][CH2:22]1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 86695204HCID 86695204, compound

Product 1

HCID 86695206HCID 86695206, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of tert-butyl N-(4-[[(3R)-3-(carbamoylmethyl)-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2 (6),9,11-tetraen-12-yl]oxy]-1-methylcyclohexyl)carbamate (100 mg, 0.22 mmol, 1.00 equiv) in dichloromethane (5.0 mL) was added hydrochloric acid (6 N, 0.3 mL) at 0° C. The resulting solution was stirred for 2 h at room temperature and concentrated under vacuum. The crude product (90 mg) was purified by preparative HPLC under the following conditions (Waters): column: XBridge Prep C18 OBD column: 5 um, 19*150 mm, mobile phase: water with 0.05% NH4HCO3 and CH3CN (5% CH3CN up to 16% in 2 min, hold 16% in 11 min, up to 95% in 2 min, down to 5% in 2 min); flow rate: 20 mL/min; UV detection at 254 & 220 nm. This resulted in 28.4 mg (36%) of 2-[(3R)-12-[(4-amino-4-methylcyclohexyl)oxy]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-3-yl]acetamide as a white solid. MS: m/z 361 (M+H)+.

Workup

  1. concentrationconcentrated under vacuum
  2. customThe crude product (90 mg) was purified by preparative HPLC under the following conditions (Waters)
  3. waitcolumn: XBridge Prep C18 OBD column: 5 um, 19*150 mm, mobile phase: water with 0.05% NH4HCO3 and CH3CN (5% CH3CN up to 16% in 2 min
  4. customin 11 min
  5. waitup to 95% in 2 min
  6. waitdown to 5% in 2 min)
  7. customThis resulted in 28.4 mg (36%) of 2-[(3R)-12-[(4-amino-4-methylcyclohexyl)oxy]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-3-yl]acetamide as a white solid

Sources & evidence

ORD record
ord-43642f6b95bc4845a38b12a843113575
Source dataset
uspto-grants-2015_12
Patent number
US09212190B2

Reaction notes

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