unstructuredio/SCORE-Bench · Datasets at Hugging Face

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as described herein.
L³ is —(OCH₂CH₂)ₚ—, —(OCHCH₃CH₂)ₚ—, —(OCH₂CHCH₃)ₚ—, —OC₂₋₁₀alkylene-, —OC 0-4 alkylene-C₃₋₁₀cycloalkylene-C 0-4 alkylene-, —OC 0-4 alkylene-phenylene-C 0-4 alkylene-, wherein the alkylene in L³
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is optionally substituted with 1-6 halogen (e.g., fluoro), and the cycloalkylene and phenylene are optionally substituted with 1-4 substituents independently selected from the group consisting of halogen, C₁₋₄alkyl, C₁₋₄haloalkyl, cyano, —OC₁₋₄alkyl, and —OC₁₋₄haloalkyl; and p is 3, 4, 5, 6, 7,
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8, 9, or 10. Preferably p is 6.
L³ may be —(OCH₂CH₂)ₚ—, such as —(OCH₂CH₂)₆—. L³ may be —OC₂₋₁₀alkylene-, such as —OC₄₋₈alkylene-, —OC₆alkylene-, or —O(CH₂)₆—.
R² is —NR²ᵃR²ᵇ, wherein R²ᵃ is hydrogen, C ₁₋₆ alkyl,
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C₁₋₆haloalkyl, C₃₋₆cycloalkyl, or —C₁₋₃alkylene-C₃₋₆суcloalkyl; R²ᵇ is hydrogen, PG², C(O)-L⁴-OH, C(O)-L⁴-OPG³, C(O)-L⁴-G¹ᵃ, C(O)-L⁵-H, C(O)-L⁵-PG¹, C(O)-L⁵ -P (O)(R¹)-G¹ᵃ, C(O)-L⁵-P(O)(OH)-G¹ᵃ, or C(O)-L⁵-P(O)(OH)-G¹ᵃ, or C(O)-L⁶-G¹ᵃ, or R²ᵃ and R²ᵇ, together with the nitrogen to which they attach
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form a protected nitrogen atom (e.g., phthalimide).
R²ᵃ and R²ᵇ may each be hydrogen (i.e., R² is NH₂).
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R²ᵃ may be hydrogen, C₁₋₆alkyl, C₁₋₆haloalkyl, C₃₋₆cycloalkyl, or —C₁₋₃alkylene-C₃₋₆cycloalkyl; wherein R²ᵇ is
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US 12,459,968 B2
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CPG O O O Si L¹ * O O P R¹ O (CH₂CH₂O)ₘ O P R¹ 1-20 (OCH₂CH₂)ₚ NHR²ᵃ
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(i-e)
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Illustrated in Scheme 2 is a representative synthesis showing implementation of steps (g)-(i) with particular A, L², L³, and R²ᵇ groups.

The functionalized solid support of formula (I-e) (e.g., where R²ᵃ is hydrogen) may be further processed to provide additional intermediates of the invention by reaction with succinic anhydride to provide the functionalized solid support of formula (I), wherein R²ᵇ is C(O)—CH₂CH₂COOH, in the form of formula (I-f)


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Scheme 3
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CPG O O O Si L¹ * O O P R¹ (CH₂CH₂O)ₘ O P R¹ 1-20 (OCH₂CH₂)ₚ NH₂ O O O
(i-e2)
CPG O O O Si L¹ * O O P R¹ O (CH₂CH₂O)ₘ O P R¹ 1-20 (OCH₂CH₂)ₚ H N O (CH₂)₂ O OH
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(i-fl)
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(I-f)
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A L¹ O O P R¹ O L² n O P R¹ L³ R²ᵃ N O (CH₂)₂ O OH.
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The functionalized solid support of formula (I-e) (e.g., where R²ᵃ is hydrogen) may be further processed to provide additional intermediates of the invention by reaction with a compound of formula HO—C(O)-L⁷-C(O)OH or HO—C(O)-L⁷-C(O)OPG³; to provide the functionalized solid support of formula (I), wherein R²ᵇ is C(O)-L⁷-C(O)OH or C(O)-L⁷-C(O)OPG³, in the form of formula (I-g) or (I-h)


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(I-g)
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A L¹ O O P R¹ O L² n O P R¹ L³ R²ᵃ N O L⁷ O OH
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(I-h)
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A L¹ O O P R¹ O L² n O P R¹ L³ R²ᵃ N O L⁷ O OPG³

as described herein.

L³ is —(OCH₂CH₂)ₚ—, —(OCHCH₃CH₂)ₚ—, —(OCH₂CHCH₃)ₚ—, —OC₂₋₁₀alkylene-, —OC 0-4 alkylene-C₃₋₁₀cycloalkylene-C 0-4 alkylene-, —OC 0-4 alkylene-phenylene-C 0-4 alkylene-, wherein the alkylene in L³

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is optionally substituted with 1-6 halogen (e.g., fluoro), and the cycloalkylene and phenylene are optionally substituted with 1-4 substituents independently selected from the group consisting of halogen, C₁₋₄alkyl, C₁₋₄haloalkyl, cyano, —OC₁₋₄alkyl, and —OC₁₋₄haloalkyl; and p is 3, 4, 5, 6, 7,

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8, 9, or 10. Preferably p is 6.

L³ may be —(OCH₂CH₂)ₚ—, such as —(OCH₂CH₂)₆—. L³ may be —OC₂₋₁₀alkylene-, such as —OC₄₋₈alkylene-, —OC₆alkylene-, or —O(CH₂)₆—.

R² is —NR²ᵃR²ᵇ, wherein R²ᵃ is hydrogen, C ₁₋₆ alkyl,

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C₁₋₆haloalkyl, C₃₋₆cycloalkyl, or —C₁₋₃alkylene-C₃₋₆суcloalkyl; R²ᵇ is hydrogen, PG², C(O)-L⁴-OH, C(O)-L⁴-OPG³, C(O)-L⁴-G¹ᵃ, C(O)-L⁵-H, C(O)-L⁵-PG¹, C(O)-L⁵ -P (O)(R¹)-G¹ᵃ, C(O)-L⁵-P(O)(OH)-G¹ᵃ, or C(O)-L⁵-P(O)(OH)-G¹ᵃ, or C(O)-L⁶-G¹ᵃ, or R²ᵃ and R²ᵇ, together with the nitrogen to which they attach

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form a protected nitrogen atom (e.g., phthalimide).

R²ᵃ and R²ᵇ may each be hydrogen (i.e., R² is NH₂).

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R²ᵃ may be hydrogen, C₁₋₆alkyl, C₁₋₆haloalkyl, C₃₋₆cycloalkyl, or —C₁₋₃alkylene-C₃₋₆cycloalkyl; wherein R²ᵇ is

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US 12,459,968 B2

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CPG O O O Si L¹ * O O P R¹ O (CH₂CH₂O)ₘ O P R¹ 1-20 (OCH₂CH₂)ₚ NHR²ᵃ

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(i-e)

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Illustrated in Scheme 2 is a representative synthesis showing implementation of steps (g)-(i) with particular A, L², L³, and R²ᵇ groups.

The functionalized solid support of formula (I-e) (e.g., where R²ᵃ is hydrogen) may be further processed to provide additional intermediates of the invention by reaction with succinic anhydride to provide the functionalized solid support of formula (I), wherein R²ᵇ is C(O)—CH₂CH₂COOH, in the form of formula (I-f)

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Scheme 3

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CPG O O O Si L¹ * O O P R¹ (CH₂CH₂O)ₘ O P R¹ 1-20 (OCH₂CH₂)ₚ NH₂ O O O

(i-e2)

CPG O O O Si L¹ * O O P R¹ O (CH₂CH₂O)ₘ O P R¹ 1-20 (OCH₂CH₂)ₚ H N O (CH₂)₂ O OH

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(i-fl)

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(I-f)

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A L¹ O O P R¹ O L² n O P R¹ L³ R²ᵃ N O (CH₂)₂ O OH.

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The functionalized solid support of formula (I-e) (e.g., where R²ᵃ is hydrogen) may be further processed to provide additional intermediates of the invention by reaction with a compound of formula HO—C(O)-L⁷-C(O)OH or HO—C(O)-L⁷-C(O)OPG³; to provide the functionalized solid support of formula (I), wherein R²ᵇ is C(O)-L⁷-C(O)OH or C(O)-L⁷-C(O)OPG³, in the form of formula (I-g) or (I-h)

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(I-g)

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A L¹ O O P R¹ O L² n O P R¹ L³ R²ᵃ N O L⁷ O OH

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(I-h)

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A L¹ O O P R¹ O L² n O P R¹ L³ R²ᵃ N O L⁷ O OPG³