Trimethylsilyldiazomethane → methyl 2-((1S,4S)-4-((tert-butoxycarbonyl)amino)-1-(3-(trifluoromethyl)-5,6,7,8-tetrahydro-1,6-naphthyridine-6-carbonyl)cyclopent-2-en-1-yl)acetate

HRID 1747130Notes

Reaction equation

HRID 1747130 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]1[CH2:13][C@@:12]([CH2:30][C:31]([OH:33])=[O:32])([C:14]([N:16]2[CH2:25][CH2:24][C:23]3[N:22]=[CH:21][C:20]([C:26]([F:29])([F:28])[F:27])=[CH:19][C:18]=3[CH2:17]2)=[O:15])[CH:11]=[CH:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:34][Si](C=[N+]=[N-])(C)C>CO>[C:1]([O:5][C:6]([NH:8][C@H:9]1[CH2:13][C@@:12]([CH2:30][C:31]([O:33][CH3:34])=[O:32])([C:14]([N:16]2[CH2:25][CH2:24][C:23]3[N:22]=[CH:21][C:20]([C:26]([F:28])([F:29])[F:27])=[CH:19][C:18]=3[CH2:17]2)=[O:15])[CH:11]=[CH:10]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 167693TrimethylsilyldiazomethaneHCID 867081372-((1S,4S)-4-((tert-butoxycarbonyl)amino)-1-(3-(trifluoromethyl)-5,6,7,8-tetrahydro-1,6-naphthyridine-6-carbonyl)cyclopent-2-en-1-yl)acetic acid

Product 1

HCID 86708138methyl 2-((1S,4S)-4-((tert-butoxycarbonyl)amino)-1-(3-(trifluoromethyl)-5,6,7,8-tetrahydro-1,6-naphthyridine-6-carbonyl)cyclopent-2-en-1-yl)acetate

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of the product of Step A (436 mg, 0.84 mmol, 1 eq) in methanol (20 mL) at 0° C. was added trimethylsilyl diazomethane (5 mL of a 2 M solution in hexanes, 10 mmol, 11.9 eq) until the yellow color persisted. The yellow solution was concentrated. Purification by chromatography (24 g column) eluting with 40 to 80% EtOAc/heptane afforded the product of Step B. 1H NMR (CHLOROFORM-d) δ: 8.70 (s, 1H), 7.69 (s, 1H), 6.37 (d, J=5.4 Hz, 1H), 5.87 (d, J=5.4 Hz, 1H), 4.98 (d, J=17.4 Hz, 1H), 4.63-4.83 (m, 3H), 4.07-4.20 (m, 1H), 3.79-3.93 (m, 1H), 3.64 (s, 3H), 3.08-3.19 (m, 2H), 3.04 (d, J=15.9 Hz, 1H), 2.62 (dd, J=13.4, 7.1 Hz, 1H), 2.46 (d, J=15.7 Hz, 1H), 2.01-2.12 (m, 1H), 1.43 (s, 9H). Calculated for C23H28F3N3O5: 506.2 (M+23). found: 506.2.

Workup

  1. concentrationThe yellow solution was concentrated
  2. customPurification by chromatography (24 g column)
  3. washeluting with 40 to 80% EtOAc/heptane

Sources & evidence

ORD record
ord-d0150ff91c0b4bcbb4651fe3a98378ad
Source dataset
uspto-grants-2015_10
Patent number
US09150532B2

Reaction notes

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