Trifluoroacetic acid → 3-Hydroxyisobenzofuran-1(3H)-one

HRID 735586Notes

Reaction equation

NCC1C=C(NC([O:17][CH2:18][CH2:19][C:20]2C=C[C:23](C(NC3C=C4C(=CC=3)C(N(C(OC(C)(C)C)=O)C(OC(C)(C)C)=O)=NC=C4)C(O)=O)=[CH:22][C:21]=2C)=O)C=CC=1S(CC)(=O)=O.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.[C:90]([OH:96])([C:92](F)(F)F)=[O:91]>>[OH:91][CH:90]1[C:92]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[C:18](=[O:17])[O:96]1

Participants

Reactant 3

HCID 6422Trifluoroacetic acid

HCID 2724699PyBOP

HCID 578427962-(4-(2-(3-(Aminomethyl)-4-(ethylsulfonyl)phenylcarbamoyloxy)ethyl)-3-methylphenyl)-2-(1-(bis(tert-butoxycarbonyl)amino)isoquinolin-6-ylamino)acetic acid

Product 1

HCID 38042593-Hydroxyisobenzofuran-1(3H)-oneYield 35%

Procedure

Using a procedure analogous to that used to prepare Example 28, 31D (400 mg, 0.51 mmol) was cyclized with PyBOP instead of BOP, deprotected with TFA, and purified by reverse phase HPLC to give Example 31 (100 mg, 35%) as a tan solid. 1H NMR (400 MHz, CD3OD) δ ppm 1.09-1.24 (m, 3 H) 2.27 (s, 2 H) 2.49 (s, 2 H) 2.67-2.88 (m, 1 H) 3.05-3.17 (m, 1 H) 3.22-3.28 (m, 2 H) 4.05 (d, J=9.89 Hz, 0.5 H) 4.13-4.25 (m, 0.5 H) 4.29-4.39 (m, 1 H) 5.01-5.12 (m, 2 H) 5.14-5.18 (m, J=3.30 Hz, 1 H) 6.43 (none, 1 H) 6.68 (d, J=2.75 Hz, 1 H) 6.70-6.78 (m, J=5.50 Hz, 1 H) 6.78-6.86 (m, 1 H) 6.92-7.16 (m, 2.5 H) 7.21 (m, 0.5 H) 7.44 (m, 0.5 H) 7.51 (s, 0.5 H) 7.65-7.74 (m, 1 H) 7.90-8.02 (m, 1 H) 8.76-8.92 (m, J=6.05 Hz, 1 H). MS (ESI) m/z 574.18 (M+H)+.

Workup

custompurified by reverse phase HPLC

Sources & evidence

ORD record: ord-3dd122e0e62e4fd8b272ad0670402c45
Source dataset: uspto-grants-2009_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07592331B2

Reaction notes

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