2-((Tert-butyldimethylsilyl)oxy)acetaldehyde → HCID 86727504, compound

HRID 519120Notes

Reaction equation

HRID 519120 reaction equation
[ClH:1].[CH:2]([C:5]1[CH:18]=[C:17]2[C:8]([N:9]3[C:14]([CH2:15][O:16]2)=[N:13][NH:12][C:11](=[O:19])[C@H:10]3[CH3:20])=[CH:7][C:6]=1[C@H:21]([C:23]1([CH3:27])[CH2:26][NH:25][CH2:24]1)[CH3:22])([CH3:4])[CH3:3].[Si]([O:35][CH2:36][CH:37]=O)(C(C)(C)C)(C)C.[BH3-]C#N.[Na+]>CO.C(O)(=O)C>[ClH:1].[OH:35][CH2:36][CH2:37][N:25]1[CH2:24][C:23]([C@@H:21]([C:6]2[CH:7]=[C:8]3[C:17](=[CH:18][C:5]=2[CH:2]([CH3:3])[CH3:4])[O:16][CH2:15][C:14]2[N:9]3[C@H:10]([CH3:20])[C:11](=[O:19])[NH:12][N:13]=2)[CH3:22])([CH3:27])[CH2:26]1

Participants

6

Reactant 3

HCID 41877882-((Tert-butyldimethylsilyl)oxy)acetaldehydeHCID 5003444Sodium cyanoborohydrideHCID 86727501HCID 86727501, compound

Product 1

HCID 86727504HCID 86727504, compoundYield 31%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 887MethanolSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of (R)-7-isopropyl-4-methyl-6-[(R)-1-(3-methyl-azetidin-3-yl)-ethyl]-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one hydrochloric acid (Example #133, Step G, 0.083 g, 0.233 mmol) in MeOH (3 mL) and acetic acid (0.3 mL) was added 2-((tert-butyldimethylsilyl)oxy)acetaldehyde (0.122 g, 0.699 mmol) and the reaction mixture was stirred at 70° C. overnight. NaBH3CN (0.073 g, 1.164 mmol) was added and the reaction mixture was stirred at 70° C. for 1 h. The reaction mixture was cooled to ambient temperature. The solvent was removed in vacuo and the residue was purified by prep-HPLC (Table 3, Method 26) to give (R)-6-{(R)-1-[1-(2-hydroxy-ethyl)-3-methyl-azetidin-3-yl]-ethyl}-7-isopropyl-4-methyl-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one hydrochloric acid (0.0291 g, 31%) as a solid. 1H NMR (CD3OD-d4, 400 MHz): δ 7.04 (s, 1H), 6.84 (s, 1H), 4.81-4.78 (m, 1H), 4.62 (s, 2H), 4.15 (d, J=10.8 Hz, 1H), 4.04 (d, J=10.8 Hz, 1H), 3.93 (d, J=10.8 Hz, 1H), 3.86 (d, J=10.8 Hz, 1H), 3.77-3.69 (m, 2H), 3.38 (m, 2H), 3.12-3.04 (m, 2H), 1.56 (s, 3H), 1.45 (d, J=6.8 Hz, 3H), 1.42-1.35 (m, 3H), 1.34-1.27 (m, 3H), 1.19-1.12 (m, 3H). LC/MS (Table 1, Method 4) Rt=1.761 min.; MS m/z: 401 [M+H]+. SFC (Table 1, Method 28) Rt=5.52 min.

Workup

  1. stirringthe reaction mixture was stirred at 70° C. for 1 h
  2. temperatureThe reaction mixture was cooled to ambient temperature
  3. customThe solvent was removed in vacuo
  4. customthe residue was purified by prep-HPLC (Table 3, Method 26)

Sources & evidence

ORD record
ord-ebf9f583e83346ee9c0cf31e3b5c2f66
Source dataset
uspto-grants-2015_08
Patent number
US09115151B2

Reaction notes

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