Methyl(2S)-2-(tert-butoxy)-2-[(22S)-17-fluoro-5-(2-hydroxypropan-2-yl)-4,22,28-trimethyl-21,27-dioxa-1,7,34-triazahexacyclo[26.2.2.16,9.110,14.02,7.015,20]tetratriaconta-2,4,6(34),8,10(33),11,13,15(20),16,18-decaen-3-yl]acetate → (2S)-2-[(22S)-17-fluoro-5-(2-hydroxypropan-2-yl)-4,22,28-trimethyl-21,27-dioxa-1,7,34-triazahexacyclo[26.2.2.16,9.110,14.02,7.015,20]tetratriaconta-2,4,6(34),8,10,12,14(33),15(20),16,18-decaen-3-yl]-2-[(2-methylpropan-2-yl)oxy]acetic acid

HRID 1482150Notes

Reaction equation

[C:1]([O:5][C@@H:6]([C:11]1[C:40]([CH3:41])=[C:39]([C:42]([OH:45])([CH3:44])[CH3:43])[C:38]2=[N:46][C:35]3=[CH:36][N:37]2[C:12]=1[N:13]1[CH2:51][CH2:50][C:16]([CH3:52])([O:17][CH2:18][CH2:19][CH2:20][CH2:21][C@H:22]([CH3:49])[O:23][C:24]2[CH:25]=[CH:26][C:27]([F:48])=[CH:28][C:29]=2[C:30]2[CH:47]=[C:34]3[CH:33]=[CH:32][CH:31]=2)[CH2:15][CH2:14]1)[C:7]([O:9]C)=[O:8])([CH3:4])([CH3:3])[CH3:2].C(O[C@@H](C1C(C)=CC2=NC3=C(Cl)N2C=1N1CCC(C)(OCCCC[C@H](C)OC2C=CC(C)=CC=2C2C=C3C=CC=2)CC1)C(O)=O)(C)(C)C>>[C:1]([O:5][C@@H:6]([C:11]1[C:40]([CH3:41])=[C:39]([C:42]([OH:45])([CH3:44])[CH3:43])[C:38]2=[N:46][C:35]3=[CH:36][N:37]2[C:12]=1[N:13]1[CH2:14][CH2:15][C:16]([CH3:52])([O:17][CH2:18][CH2:19][CH2:20][CH2:21][C@H:22]([CH3:49])[O:23][C:24]2[CH:25]=[CH:26][C:27]([F:48])=[CH:28][C:29]=2[C:30]2[CH:47]=[C:34]3[CH:33]=[CH:32][CH:31]=2)[CH2:50][CH2:51]1)[C:7]([OH:9])=[O:8])([CH3:2])([CH3:3])[CH3:4]

Participants

Reactant 2

HCID 118316385Methyl(2S)-2-(tert-butoxy)-2-[(22S)-17-fluoro-5-(2-hydroxypropan-2-yl)-4,22,28-trimethyl-21,27-dioxa-1,7,34-triazahexacyclo[26.2.2.16,9.110,14.02,7.015,20]tetratriaconta-2,4,6(34),8,10(33),11,13,15(20),16,18-decaen-3-yl]acetate

HCID 118332041(2S)-2-(tert-Butoxy)-2-[(22S)-8-chloro-4,17,22,28-tetramethyl-21,27-dioxa-1,7,34-triazahexacyclo[26.2.2.16,9.110,14.02,7.015,20]tetratriaconta-2,4,6(34),8,10(33),11,13,15(20),16,18-decaen-3-yl]acetic acid

Product 1

HCID 118316386(2S)-2-[(22S)-17-fluoro-5-(2-hydroxypropan-2-yl)-4,22,28-trimethyl-21,27-dioxa-1,7,34-triazahexacyclo[26.2.2.16,9.110,14.02,7.015,20]tetratriaconta-2,4,6(34),8,10,12,14(33),15(20),16,18-decaen-3-yl]-2-[(2-methylpropan-2-yl)oxy]acetic acidYield 11.7%

Procedure

Prepared in 11.7% yield from methyl(2S)-2-(tert-butoxy)-2-[(22S)-17-fluoro-5-(2-hydroxypropan-2-yl)-4,22,28-trimethyl-21,27-dioxa-1,7,34-triazahexacyclo[26.2.2.16,9.110,14.02,7.015,20]tetratriaconta-2,4,6(34),8,10(33),11,13,15(20),16,18-decaen-3-yl]acetate following the procedure for (2S)-2-(tert-butoxy)-2-[(22S)-8-chloro-4,17,22,28-tetramethyl-21,27-dioxa-1,7,34-triazahexacyclo[26.2.2.16,9.110,14.02,7.015,20]tetratriaconta-2,4,6(34),8,10(33),11,13,15(20),16,18-decaen-3-yl]acetic acid. 1H NMR (500 MHz, DMSO-d6) δ 8.15 (s, 1H), 8.00 (d, J=7.3 Hz, 1H), 7.92 (s, 1H), 7.56 (t, J=7.7 Hz, 1H), 7.38 (d, J=7.3 Hz, 1H), 7.24-7.13 (m, 3H), 5.98 (br. s., 1H), 4.61 (br. s., 1H), 3.80 (t, J=11.6 Hz, 1H), 3.60 (t, J=12.1 Hz, 1H), 3.44 (d, J=14.7 Hz, 4H), 3.25 (br. s., 1H), 2.64 (d, J=9.5 Hz, 1H), 2.42 (s, 3H), 1.91-1.75 (m, 5H), 1.71 (s, 10H), 1.52 (br. s., 1H), 1.19 (s, 3H), 1.15 (s, 9H), 1.07 (d, J=5.9 Hz, 3H); LCMS (ESI, M+1): 686.4.

Sources & evidence

ORD record: ord-0a3fc0b2e4b0422e97e5918c829f4ecb
Source dataset: uspto-grants-2016_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09409922B2

Reaction notes

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