Hydrochloric Acid → HCID 89781229, compound

HRID 1503911Notes

Reaction equation

HRID 1503911 reaction equation
[OH:1][CH:2]([CH2:31][CH3:32])[CH2:3][C@H:4]1[CH2:15][CH2:14][C:13]2[S:12][C:11]3[N:10]=[CH:9][N:8]=[C:7]([NH:16][CH:17]4[CH2:22][CH2:21][CH:20]([NH:23]C(=O)OC(C)(C)C)[CH2:19][CH2:18]4)[C:6]=3[C:5]1=2.Cl>ClCCl>[NH2:23][CH:20]1[CH2:21][CH2:22][CH:17]([NH:16][C:7]2[C:6]3[C:5]4[C@@H:4]([CH2:3][CH:2]([OH:1])[CH2:31][CH3:32])[CH2:15][CH2:14][C:13]=4[S:12][C:11]=3[N:10]=[CH:9][N:8]=2)[CH2:18][CH2:19]1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 89691360HCID 89691360, compound

Product 1

HCID 89781229HCID 89781229, compoundYield 79.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A 50-mL round-bottom flask was charged with 30.1 (130 mg, 0.28 mmol, 1.00 equiv) and dichloromethane (10 mL) and cooled to 0° C. Then hydrochloric acid (12 M, 2.0 mL) was added and the resulting solution was stirred for 3 h at room temperature. After 3 h, the mixture was concentrated under vacuum. The pH value of the solution was adjusted to 8 with saturated aqueous sodium carbonate and then the solution was extracted with 2×40 mL of ethyl acetate. The organic layers were combined and dried over sodium sulfate and concentrated under vacuum to give 1-[(3R)-12-[(4-aminocyclohexyl)amino]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-3-yl]butan-2-ol (80 mg, crude) as a colorless oil. To a solution of this material (80 mg, crude) in methanol (5 mL) was added HCHO (37%, 0.8 mL). The reaction was stirred for 1 h at room temperature. Then NaBH3CN (33.9 mg, 0.54 mmol, 2.44 equiv) was added and the resulting solution was stirred for an additional 2 h at ambient temperature and concentrated under vacuum. The crude product (80 mg) was purified by preparative HPLC(SHIMADZU) under the following conditions: column: SunFire Prep C18, 19*150 mm 5 um; mobile phase: water with 0.1% HCOOH and CH3CN; UV detection at 254 nm. The product-containing fractions were collected and evaporated to remove the water and CH3CN to give (2R)-1-[(3R)-12-[[4-(dimethylamino)cyclohexyl]oxy]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-3-yl]butan-2-ol formate (I-52, 8.6 mg) as a white solid and (2S)-1-[(3R)-12-[[4-(dimethylamino)cyclohexyl]oxy]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-3-yl]butan-2-ol formate (I-54, 5.9 mg) as a grey solid, respectively.

Workup

  1. waitAfter 3 h
  2. concentrationthe mixture was concentrated under vacuum
  3. extractionthe solution was extracted with 2×40 mL of ethyl acetate
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-bc87d2de584c45afbf928caf4a38b7c2
Source dataset
uspto-grants-2015_12
Patent number
US09212190B2

Reaction notes

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